key: cord-0034102-umtd0cxx
authors: nan
title: 10th Asian Congress of Pediatric Nephrology 2008 (ACPN 2008) Innovation in Prevention and Therapeutic Strategies August 28–30, 2008 Centara Grand & Bangkok Convention Centre at Central World, Bangkok, Thailand
date: 2009-03-01
journal: Pediatr Nephrol
DOI: 10.1007/s00467-008-1094-5
sha: 90f83c45455b22e0c9ac03aa5468a6ba530cc1c7
doc_id: 34102
cord_uid: umtd0cxx

nan

08.00-08.30 ISN-COMGAN CME for Thailand Theme: Strategies to prevent CKD progression 08.30-09.00 09.00-09.30 09.30-10.00 10.00-10.30 10.30-11.00 11.00-11.30 11.30-12.00 12.00-12.30 Luncheon symposium 12.30-13.00 13. 00-13.30 Work shop (CRRT) 13.30-14.00 14. 00-14.30 14.30-15.00 15.00-15.30 Coffee break 15. 30-16.00 Work shop (CRRT) 16. 00-16.30 16.30-17.00 17.00-17.30 17.30-18.00 18.00-18.30 Opening ceremony & Plenary lecture 1 18. 30-19.00 19.00-19.30 19.30-20.00 Welcome Reception 20.00-20.30 20.30-21.00 TIME/DATE 29th August 20008 08.00-08. 30 Plenary lecture 2 & 3 08.30-09.00 09.00-09.30 09. 30-10.00 Coffee break Coffee break/Posters viewing 10.00- 10.30 Joint forum of Adult and Pediatric Symposium 1: Advances in chronic kidney diseases Symposium 2: Chronic renal failure 11.00-11.30 11.30-12.00 12.00-12.30 Luncheon symposium 12.30-13.00 13. 00-13.30 Joint forum of Adult and Pediatric Nephrology 10.30-11.00 Symposium 9: Renal tubular disorders Symposium 10: Kidney transplantation 11.00- 11.30 11.30-12.00 12.00-12.30 Luncheon symposium 12.30-13.00 13. 00-13.30 AsPNA General Assembly Meeting 13.30-14.00 14. 00-14.30 Mini review 4-6 & Free Coffee break 16. 00-16.30 Symposium 11: Systemic diseases and the kidney Symposium 12: General nephrology 16.30-17.00 17. 00-17.30 Closing remarks & Introduction to next ACPN Venue 17.30-18.00

Asia is the largest continent in the world with an estimated population approaching 4 billion, of which children under the age of 19 years constitute more than 1 billion. Unfortunately, health care delivery across the Asian continent is very heterogeneous. The more urgent issues in child health in many Asian countries encompass the control of infections, malnutrition and diarrheal diseases. However, with improvements in public health especially in urban communities, the pattern of childhood disorders has changed in many countries, resulting in a shift in the causes of mortality from infections to other chronic diseases. Therefore, although the major challenges in pediatric nephrology practice still include the management of children with acute kidney injury due to severe dehydration, sepsis and toxins, the prevention and treatment of children with chronic kidney disease is emerging as the new challenge for this millennium. The first Working Group for Pediatric Nephrology in Asia was formed in 1986, holding its first scientific meeting in Tokyo, Japan in 1988. The Asian Society of Pediatric Nephrology (AsPNA) was officially inaugurated in 1996 with a mandate to promote the development of pediatric nephrology in Asia and foster regional cooperation amongst member countries. With regional education and training as one of the main focus, quality care including both acute and chronic renal replacement therapies, as well as strategies for the prevention of chronic kidney disease, will be available more widely to the pediatric population in Asia. Data on childhood end-stage renal disease in Asia is scarce. A survey on renal replacement therapy in 12 Asian countries by Chiu MC et al in 2005 revealed that peritoneal dialysis was the major modality of dialysis in many Asian countries, with chronic ambulatory peritoneal dialysis being the main modality (64%), followed by automated peritoneal dialysis (30%), and intermittent peritoneal dialysis (6%). Although some countries have specialized hemodialysis facilites for children, however, in many Asian countries, children and adolescents are dialyzed in adult hemodialysis centers. In Asia, the majority of pediatric renal transplants are live-donor related. Patient and graft survival rates at 5 years reported in the 2005 survey were approximately 92% and 81% respectively. On the whole, renal replacement therapy is expensive in many parts of Asia, therefore financial issues limit the availability of end-stage care, especially in the developing countries. In conclusion, the challenge of this millennium for pediatric nephrology in Asia is to address this great divide in health care for children. The main focus should be on training and education, focusing on identification of children at high risk of chronic kidney disease and providing early treatment to prevent progression and the need for renal replacement therapy. At the same time, reduction of morbidity and mortality in children with acute kidney injury can be achieved using evidence-based practice which should be made easily accessible to doctors even in remote regions of the continent. Bone histomorphometry has been has been the gold standard in the evaluation and diagnosis of renal osteodystrophy (RO). The recent new definition of RO as Chronic Kidney Disease-Mineral and Bone Disorder has once again highlighted the use of bone biopsy as a powerful and diagnostic tool to determine skeletal abnormalities in chronic kidney disease. In addition, it has been recommend the inclusion of turnover (T), mineralization (M) and volume (V) in the assessment of bone histology. Thus, we apply the TMV classification in bone biopsies (BBx) obtained after double tetracycline labeling from 140 pts. aged 14±1.2 years on CCPD for 13±3 mos. All pts. were treated with Ca-based binders and daily oral calcitriol that was held for 4 weeks prior to BBx. S-PTH (1st Nichols, 1st generation), S-Alk p'tase, Ca, and P levels were determined at BBx. Twenty five percent of the patients had both normal T and M; 36% high T and M defect; 23% high T and 16% M defect alone. Sensitivity and specifity of PTH levels <400 pg/ml and alk p'tase levels <400 IU/L gave us a sensitivity of 80 and specivity of 77% for predicting patients with both normal T and M. PTH levels ≥600 pg/ml had a sensitivity of 78% and a specifity of 73 for predicting patients with high T and M defect. Current biochemical markers seemed to unhelpful in distinguishing patients with M defect alone and a bone biopsy is required for its evaluation. FGF-23 is associated with altered skeletal mineralization in individuals with normal renal function; its potential as a biomarker for mineralization in patients with chronic kidney disease remains to be defined. We demonstrated that bone formation rates correlated with PTH (r=0.44, p<0.01), but not with FGF-23. Higher FGF-23 concentrations were associated with improved osteoid thickness and osteoid maturation time. We conclude that FGF-23 may be a new biomarker for the non-invasive assessment of skeletal mineralization in patients with secondary hyperparathyroidism.

Calcium-containing phosphate binding agents and active vitamin D sterols have been widely recommended for the control of hyperphosphatemia and the prevention of secondary hyperparathyroidism. The administration of such compounds, however, contributes to the development of frequent episodes of hypercalcemia, hyperphosphatemia, adynamic osteodystrophy and vascular calcifications. On the other hand, untreated secondary hyperparathyroidism causes significant morbidity, including severe bone deformities, fractures and growth retardation in children. The availability of effective calciumfree-metal free phosphate binding agents, such as sevelamer combined with new active vitamin D sterols, such as doxercalciferol has widened the margin of safety for the treatment of secondary hyperparathyroidism. Although these agents can effectively control serum phosphorus and lower PTH levels, little is known about their effects on the skeletal lesions of secondary hyperparathyroidism. We have therefore prospectively compare the effects of calcium carbonate and sevelamer on the control of the biochemical and skeletal indices of secondary hyperparathyroidism during therapy with either calcitriol or doxercalciferol in pediatric patients treated with peritoneal dialysis. The data demonstrated that sevelamer allows for the use of higher doses of active vitamin D sterols without inducing changes in serum calcium levels and with adequate control of the skeletal lesions of secondary hyperparathyroidism, but the mineralization defect persists. Serum PTH levels between 400-600 pg/ml are associated with indices of bone formation within the normal range in the vast majority of patients after treatment with intermittent doses of active vitamin D sterols.

King Chulalongkorn Memorial Hospital, Bangkok, Thailand

Chronic kidney disease (CKD) is a new growing public health threat. Failure to prevent end-stage renal disease (ESRD) associated with a progressive increment in ESRD patients are relevant to 2 crucial issues namely (1) the insensitiveness of present diagnostic marker such as serum creatinine determination, or microalbuminuria which detects late CKD (stages 3-5; equivalent to CCr < 60 ml/min/1.73m2), but is unable to screen early CKD (stages 1,2; equivalent to CCr > 60-119 ml/min/1.73m2).

(2) Present therapeutic target aiming at suppression of proteinuria or/and controlling blood pressure although is beneficial, but not perfect, since it does not correct the mechanism of renal disease progression. In order to establish an effective preventive strategy aiming to minimize ESRD, the above crucial and unanswered problems have been integrally addressed as follows.

(1) With respect to the diagnostic marker, fractional excretion of magnesium is a highly sensitive marker for screening early CKD stages 1 and 2. FE Mg assists to initiate early therapeutic and preventive strategy under favourable environment towards renal regeneration. (2) With respect to the properly therapeutic target, we have studied the role of renal microvascular disease inducing the development of tubulointerstitial fibrosis. Accumulating evidence demonstrates oxidative stress, immunocirculating disturbance which are circulating toxins inducing glomerular endothelial cell injury and dysfunction. Glomerular endothelial dysfunction induces hemodynamic maladjustment at the efferent arteriole, a progressive reduction in peritubular capillary flow, a chronic ischemic injury to the tubulointerstitium, and eventually tublointerstitial fibrosis. Therefore, correction of hemodynamic maladjustment with multidrug vasodilators (ACEI, AII receptor blocker, calcium channel blocker, antiplatelet) would be the appropriate therapeutic target.

The present failure in treating late stages of CKD (3-5 patients ) is likely to be explained by the altered vascular homeostasis observed in this group of CKD patients. We observed deficiencies in the mechanism of vascular repair namely deficiencies in VEGF, flt-1 (VEGF R1) angiopoietin-1, nitric oxide, and endothelial progenitor cell, which are essential factors for vascular angiogenesis; whereas factors opposing normal vascular repair such as VEGF R2 (KDR), angiopoietin-2 are elevated. Taken together, such alterations encompass in a default angiogenesis and renal microvascular rarefaction. In contrast, a normal or slightly impaired vascular homeostasis is encountered in early stage of CKD associated with favourable environment for renal regeneration. Thus, correction of hemodynamic maladjustment with multidrug vasodilators in the early stage of CKD can enhance peritubular capillary flow, improve renal perfusion to the tubulointerstitium, and effectively prevent the development of tubulointerstitial fibrosis. This coincides with the improved glomerular filtration rate and hence, prevents the ESRD.

In conclusion, an innovative strategy to effectively prevent ESRD can be implemented by (1) screening early stage of CKD with a novel diagnostic marker FE Mg (2) appropriately correcting the hemodynamic maladjustment with multidrug vasodilators to improve renal perfusion at the early stage of CKD.

Division of Nephrology, Ewha University School of Medicine, Seoul, Korea

It is well known that the maintenance of renal vasculature is crucial for preservation of renal function. Maintenance of glomerular capillary would help maintain glomerular filtration rate (GFR), whereas maintaining peritubular capillaries in the interstitium would be essential for providing oxygen and nutrition to the tubules and interstitial cells. Afferent and efferent arterioles also play a key role in determination of renal hemodynamics, activation of renin-angiotensin system and intra-glomerular pressure. Recent studies demonstrate a substantial repair capacity of renal microvasculature in various spectrum of renal diseases, however this recovery process of the kidney is compromised in chronic kidney disease (CKD). Although an early proliferative response of the glomerular and peritubular capillary endothelium was noted with a loss of functioning nephron mass, the proliferation was not sustained with a progressive loss of the endothelium due to unchecked apoptosis over time. The loss of the glomerular endothelium predisposes to activation of platelets and the coagulation system that favors capillary collapse and the development of glomerulosclerosis. The degree of glomerular and peritubular capillary loss in CKD correlates with the severity of glomerulosclerosis and interstitial fibrosis. These changes in renal microvasculature were preceded by an altered expression of vascular survival factor and/or anti-angiogenic factors, such as vascular endothelial growth factor (VEGF) and thrombosponsin-1. Interestingly, macrophage-dervied cytokine and vasoactive mediators II was known to play a role in regulation of the expression of angiogenesis-modulating factor in the kidney.

There have been several lines of evidence suggesting that stimulation of endothelial proliferation might be beneficial in kidney disease. Glomerular endothelial cell proliferation plays a key role in the repair of capillaries and microaneurysms in the Thy-1 nephritis model whereas blockade of the capillary repair resulted in an aggravation of renal damage. In addition, VEGF supplement enhanced capillary repair and improved renal function in animal model of CKD.

A key role for VEGF in glomerular capillary formation has also been suggested from studies of glomerular development in neonatal rats and mice. However, although angiogenesis-modulating therapy seems to be an attractive therapeutic modality of CKD, not all studies would support the view that increased angiogenesis prevents renal disease progression. For example, in diabetic nephropathy, the most prevalent cause of CKD in these days, an implication of modulating renal microvascular angiogenesis as therapeutic tool seems to depend on the stage of diabetic nephropathy and associated complication in individual patients. Further studies on the role of the microvasculature in progressive renal disease are necessary, and the insights may lead to new therapeutic approaches for the treatment of CKD, which shows the most remarkable worldwide epidemic nowadays.

The paediatric imperative is to promote growth and development. Nutrition is important for that objective, particularly during the infantile phase. Recent research has moved away from considering adequate intake resulting in protein calorie malnutrition to use OF the term "cachexia". There may be a loss of lean body mass combined with normal, or even, increased fat mass, high resting energy expenditure and inadequate response to nutrient supplementation. Research has also highlighted that nutritional factors may be implicated in progression of cardiovascular disease which is known to be accelerated in CKD. Hence, the need to consider the nutritional status of the child with regular assessment and support as CKD advances.

The nutritional management requires expert dietetic support and a multidisciplinary team approach. Basic anthropometric measurements should be taken at every clinic visit, regular clinic assessment combined with dietary assessment via diaries or dietary recall in clinic. The nutritional prescription should be based upon growth, biochemical and haematological data as well as consideration of relevant medications such as phosphate binders, iron and micronutrient supplements and salt balance. Each child has individualised nutritional requirements which should be given by the oral route whenever possible. Inadequate intakes to maintain adequate growth velocity require the early introduction of enteral feeding via the gastrostomy or nasogastric route. Intensive nutritional support requires dietetic and medical time and needs to take into account the psychosocial needs of the family. This may all help to promote normal growth without the need for the routine use of recombinant human growth hormone.

Children's Mercy Hospital, USA

The International Pediatric Peritonitis Registry (IPPR) and the International Pediatric Peritoneal Dialysis Network (IPPN) are collaborative efforts that were established to collect data related to the provision of peritoneal dialysis (PD) to children and to use that data to improve patient care on a global basis. The IPPR created an online database to record information on the etiology and treatment of peritonitis in 47 centers from 14 countries. Global variation was noted in the 501 peritonitis cases identified in terms of causative organisms, frequency of staphylococcal methicillin resistance, incidence of culture-negative peritonitis and in the antibiotic susceptibility patterns. Gram-negative peritonitis was associated with the poorest outcome and was most often seen in patients < 5 years old and in those conducting frequent exit-site care with mupirocin. Invitro antibiotic susceptibility data revealed only 69% of gram positive organisms and 80% of gram negative organisms to be susceptible to a first generation cephalosporin and an aminoglycoside, respectively, prompting consideration for alternative recommendations regarding empiric antibiotic therapy. In 89% of cases, there was full functional recovery with less frequent complete resolution occurring among the 52 patients who experienced a relapsing infection. The IPPN has expanded the goals of the registry to monitor overall PD performance and complications and to assess the association between PD practice and outcome. To date, nearly 600 patients have been enrolled in the Network from 76 centers in 27 countries. Preliminary data has revealed global differences in the distribution of PD modality selection, the frequency of growth retardation and growth hormone usage and in the management of secondary hyperparathyroidism. Current analyses are being conducted to assess the correlation between PET transport capacity, dialysis prescription and cardiovascular disease, in addition to the reasons for hospitalization. Continued data collection and analysis should help define global standards for pediatric PD care.

The goal of hemodialysis is to optimize patient well-being by appropriate solute and fluid removal. The prescription for each session should, a)minimize dialysis related symptoms, b) maximize fluid and solute removal, and c) reduce inderdialytic morbidity. Methods Review of the literature and clinical experience describing measures of dialysis adequacy,and options available to minimize symptoms related to solute and fluid removal.

The average weekly plasma urea, the % urea reduction, the clearance (Kt/V) of urea, the plasma albumin,have each been suggested as markers of dialysis adequacy, but none should be used in isolation. Nutritional status,as measured by normalized protein catabolic rate (nPCR) as well as clinical anthropometry and growth must also be considered. Similarly, hypertension and abnormal cardiac function, anemia, calcium/phosphate and PTH disturbances must be minimized. Achievement of these goals, within the limitations of thrice weekly HD, may be improved by use of sodium ramping, ultrafiltration profiles, and non-invasive blood volume monitoring. Conclusion This review will consider the value and limitations of sodium ramping, ultrafiltration profiles, and blood volume monitoring for prescription of pediatric hemodialysis. Also, simple estimates of nPCR and Kt/Vurea, which have been validated in children will be included. Finally, the limitations of thrice weekly HD will be considered.

Department of Nephrourology, Gt Ormond St Hospital for Children NHS Trust, UK Treatment with dialysis and transplantation is now highly successful, but despite this the incidence of death from CVD has not improved, and many young patients will die from cardiovascular events; the risk of death for a such a child is 30 times that of the normal population, and the chances of death from CVD for a young adult on dialysis is equivalent to that of an 85 year old. Lifespan is reduced by 40-60 years in children on dialysis and by 20 to 30 years if transplanted, with about 50% of deaths due to CVD.

There are many factors contributing to this high incidence of CVD. One of the most important is fluid overload and LVH. Another cause, about which there is currently much interest, is vascular calcification. Abnormal bone mineral metabolism (CKD-metabolic bone disorder [MBD] ) is an important cause of vascular damage and calcification, and there is now plenty of evidence to link this to mortality. We have undertaken studies of vascular structure (carotid intima-media thickness [IMT] ), function (pulse wave velocity) and coronary calcification in children on dialysis and correlated the results with plasma phosphate, PTH, vitamin D and calcification inhibitors. We have found significantly worse results for these vascular parameters in children with PTH levels > 2 × the upper limit of normal and when levels of 1,25(OH)2D are either above or below the normal range.

To address this further, we obtained arteries that would normally be discarded from children undergoing insertion of peritoneal dialysis catheters or transplantation. We quantified the calcium (Ca) load in the arteries and correlated it with clinical, biochemical and vascular measures. We found that Ca accumulation begins pre-dialysis, but it is the induction of VSMC apoptosis in dialysis that is the key event by disabling VSMC defence mechanisms thus leading to overt calcification, eventually with clinically detectable vascular damage. Therefore, the identification of factors that lead to VSMC death in dialysis will be of prime importance in preventing vascular calcification.

A new area of research is that of myocardial dysfunction in association with intradialytic hypotension. Areas of myocardium develop regional motion wall defects, called myocardial stunning which, although initially temporary, may lead on to permanent myocardial damage.

Unravelling the processes of vascular injury in children with CKD will enable new treatments and even preventative therapies that will help reduce the burden of CVD when these children reach adulthood Renal parenchymal damage after urinary tract infection (UTI) and reflux nephropathy may lead to chronic renal failure in children and young adults. Vesicoureteral reflux has known to be related with genetic background. Several genetic mediators including renin angiotensin system (RAS), VEGF and TGF-β1 have been implicated in initiating and regulating parenchymal damage leading to renal scarring. This study was designed to investigate whether the genetic polymorphisms of RAS, VEGF and TGF-β1, were associated with the susceptibility to UTI, vesicoureteral reflux (VUR), and subsequent renal scarring. RAS There was no difference in the distribution of the ACE II, ID and DD genotype and the AT1 A1166C transition between the patients with primary VUR and the controls. However, the incidence of AT2 A-1332G transition was significantly lower in primary VUR patients (p=0.047). Furthermore, in the case of combination of ACE and AT2 gene, a significantly lower incidence of primary VUR was seen with II genotype of ACE and A-1332G transition in the AT2 receptor gene(p=0.003). Concerning the risk factors of primary VUR, the grade of reflux was significantly higher in AT2 A-1332G transition group compare to the group without transition (p=0.044, mean grade of reflux 3.54±1.17 vs 2.83±1.43). Also, ACE ID/DD genotypes with AT2 A-1332G transition group had higher grade of reflux than ACE II genotype without AT2 A-1332G transition (p=0.025, mean grade of reflux 3.48±1.21 vs 2.47± 1.36). Other risk factors did not show much difference in the distribution of ACE, AT1 and AT2 genotypes. These findings indicate that low rate of incidence but high grade of primary VUR is seen in AT2 A-1332G transition group, at least in the Korean population.

In both UTI and VUR groups, there was an increase in frequency of the VEGF -460 CC (control, 4.3; UTI, 15.9 ; VUR, 17.8%; P<0.05), TGF-β1 -509 CC (control, 8.7; UTI, 34.6; VUR, 35 .1%; P<0.001), and TGF-β1 -800 GG genotypes (control, 19.1; UTI, 40.5; VUR, 40.4%; P<0.05 ). An increase in the TGF-β1 +869 CC (scar-positive, 35.4; scar-negative, 10.3%; P<0.05) and a decrease in the +869 TC genotype (scar-positive, 29.2; scar-negative, 55.2%; P<0.05) were observed in the scar-positive subjects. There were no differences in +405 VEGF genotype frequencies. The VEGF T-460C and the TGF-β1 C-509T, G-800A, and T869C polymorphisms could be genetic markers of the process of UTI and VUR.

Urinary tract infection (UTI) is still one of the most common bacterial infections in children. Prior to the advent of antibiotics, about 20% of newborns and infants died from acute UTI. Fortunately, mortality today is very low. However the acute and long term morbidity of UTI particularly in this group of children is still considerable.

The standard of care for children especially very young children diagnosed to have UTI was to perform imaging procedures mainly ultrasound, micturiting cystourethrogram (MCUG) and DMSA scans to look for urinary tract abnormalities and renal scarring. The most common abnormality found was vesicoureteric reflux (VUR). VUR was said to predispose to recurrent UTI especially recurrent acute pyelonephritis which may lead on to progressive renal scarring. Progressive renal scarring may result in hypertension or kidney failure or both. This formed the basis of the therapeutic modalities to avoid further renal parenchymal damage, namely antibiotic prophylaxis to maintain urine sterility or surgery to eliminate the reflux.

However evidence thus far has not clearly shown the benefits of either antibiotic prophylaxis or surgery in the prevention of further renal damage. Newer randomized studies albeit not placebo controlled have thrown doubt as to the effectiveness of antibiotic prophylaxis in the prevention of symptomatic UTI and renal scarring.

Hence, treating every UTI promptly and adequately may be the way forward. We however, eagerly await the results of the RIVUR study (Randomized Intervention for Children with Vesicoureteral Reflux) -a randomized, double blind placebo control study on whether prophylactic antibiotics prevents renal scarring and UTI in children with VUR. Urinary tract infection (UTI) is a common ascending infection of fecal uropathogens. First UTI commonly develops in infancy and frequently recurs. Thus, infants with first UTI should be investigated for the host risk factors and managed properly to prevent recurrent UTI and subsequent renal scarring. A series of host risk factors for childhood UTI are listed up in Nelson Textbook of Pediatrics. Female gender is on top of them, followed by uncircumcised males.

Female preponderance of childhood UTI has been a well-known phenomenon but infantile UTI has developed predominantly in the male gender. It was noted in mid 1980s that a majority of infantile UTI developed in male infants who were not circumcised. In several large cohort studies, the incidences of UTI in male infants without neonatal circumcision were 10-20 times more prevalent than in male infants with neonatal circumcision. This high incidence of UTI in uncircumcised male infants is attributed to male preponderance and high male to female ratio of infantile UTI. Despite the definite protective effect of neonatal circumcision against UTI in early infancy of male infants, AAP (1999) still adopted a neutral or anticircumcision stance. Although others were concerned about the AAP policy (2003), a recent systemic review (2005) also did not recommend routine neonatal circumcision.

A majority of uncircumcised neonates have nonretractile prepuces (physiologic or congenital phimosis), which makes penile hygiene difficult. Preputial sac of a nonretractile prepuce becomes a reservoir of uropathogens which can be a source of infantile UTI, until a nonretractile prepuce became spontaneously retractile.

In prepubertal children with phimosis who were referred for circumcision, topical application of moderate and highly potent steroids for 4-8 weeks has been proved as successful (65-95%) in resolving phimosis. Even in infants, who were diagnosed with first UTI and found to have nonretractile physiologic phimosis, hydrocortisone cream of lowest potency and physiotherapy (gentle retraction) were highly successful (96.1%). In infants whose prepuces became retractile after topical hydrocortisone, recurrent UTI developed less frequently for the following 1 year than in infants with persistently nonretractile prepuces (7.1% vs 29.6%). A majority of male children, who were referred for aseptic pyuria and asymptomatic bacteriuria, were found to have nonretractile prepuces. Successful topical application of hydrocortisone with physiotherpy eliminated aseptic pyuria and asymptomatic bacteriuria.

Topical application of hydrocortisone with physiotherapy is a simple, economical, safe and effective therapy for a nonretractile physiologic phimosis and it should be considered as an ideal alternative to the much debated neonatal circumcision. Introduction: Acute kidney injury (AKI) represents a common and devastating problem in clinical medicine. The lack of early biomarkers for AKI has lead to a delay in initiating potentially effective therapies. The objective of this presentation is to review the status of novel urinary biomarkers for AKI that have progressed to the clinical phase of the biomarker discovery process. Methods: Literature review (PubMed, MedLine) from 2000 to the present. Results: The most promising AKI biomarkers include neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and kidney injury molecule-1 (KIM-1). Conclusions: It is likely that the AKI biomarkers will be useful for timing the initial insult and assessing the duration and severity of AKI. Based on the differential expression of the biomarkers, it is also likely that the AKI panels will help distinguish between the various types and etiologies of AKI, and predict clinical outcomes. Studies to validate the sensitivity and specificity of these biomarkers in clinical samples from large cohorts and from multiple clinical situations are currently in progress, facilitated by the development of commercial tools for the reproducible measurement of these biomarkers across different laboratories. The availability of such personalized and predictive information could revolutionize renal and critical care medicine in the not-too-distant future.

Definitions of a Biomarker:

1) a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. 2) Clinical end point: a direct measure of how a patient feels, functions or survives. 3) Intermediate end point: a biomarker which is intermediate in the causal pathway between an intervention and a clinical endpoint. 4) Surrogate: a laboratory measurement or physical sign that is used in therapeutic trials as a substitute for a clinically meaningful endpoint that is expected to predict the effect of the therapy.

CKD is characterized by glomerulo-and vascular sclerosis and tubulointerstitial fibrosis regardless of the etiology. This finding suggests that after acute kidney injury, adapative changes in nephrons initiate a chronic maladaptive process cumulating in scarring. Factors identified in mediating these changes are: hemodynamic, the renin-angiotensinaldosterone system, cytokines, chemokines, growth factors, podocyte loss, dyslipidemia, specific mechanisms of tubulointerstitial fibrosis, low birth weight and low nephron number, genetic predisposition to CKD, and, proteinuria.

It is well established that proteinuria has been implicated in causing CKD progression via mesangial toxicity and tubular injury with interstitial fibrosis. It is part of the natural history of CKD and serves as a biomarker of kidney damage, a clue to the diagnosis of CKD, a risk factor for progression (causal in animal models), a modifier for efficacy of ACE inhibitor therapy in non-diabetic kidney disease, a hypothesized marker of vascular permeability (generalized endothelial dysfunction), a risk factor for cardiovascular disease (CVD) at lower levels than defined as CKD, and a hypothesized surrogate outcome for kidney disease progression and CVD reduction.

In addition to proteinuria, the cytokine, TGFß was found in urine to differentiate between histologically proven minimal change and focal segmental glomerulosclerosis pediatric patients (11.5 vs 148 pg/mg Cr, respectively, Woroniecki, RP. et al. Am J Nephrol 2008; 28(1):83-90) . Furthermore, application of urinary proteomics combined with bioinformatics, predicted the response to treatment in these patients with steroid sensitive or resistant nephrotic syndrome (Woroniecki RP, et al. Am J Nephrol 2006; 26(3) :258-67). Thus, the need for identification and measurement of potential biomarkers in prospective longitudinal cohort studies such as the Chronic Kidney Disease in Children will lead to better patient-specific targeted therapies to slow or halt the progression.

Division of Pediatric Nephrology, All India Institute of Medical Sciences, New Delhi, India Acute renal failure (ARF) is a common condition, often under recognized with severe consequences. The condition has diverse etiologies, with features ranging from mild elevation in serum creatinine to anuric renal failure. In most instances, the decline in function is secondary to tubular injury that leads to functional or structural changes in the kidney. In the absence of a standard definition & recognizing that ARF includes a spectrum of conditions, the term acute kidney injury (AKI) has been proposed to reflect the entire range of the syndrome. The term includes functional or structural abnormalities or markers of kidney damage, present <3 months. AKI is associated with increased mortality that is worsened when dialysis is needed. An unrecognized effect of AKI is the later development and progression of chronic kidney disease.

AKI is increasingly prevalent in both developed and developing countries, and is associated with considerable morbidity and mortality. There is a lack of data regarding the true incidence of AKI, its epidemiology and outcome in children. In developed countries, AKI occurs chiefly in ICUs and is associated with multiorgan failure, sepsis and high mortality. Important causes of AKI in developing countries include severe sepsis, dehydration due to gastroenteritis, infections (severe malaria, leptospirosis, hemolytic uremic syndrome) and postinfectious glomerulonephritis. Many causes of AKI in developing countries can be prevented by low-cost interventions at individual, community and regional levels.

Therapy of AKI is supportive with attention to fluid and electrolyte status, ensuring adequate nutrition and treatment of complications. There is limited role for treatment with low-dose dopamine or frusemide. Patients with AKI should be followed up to examine for evidence of chronic kidney disease (renal dysfunction, proteinuria or hypertension).

Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, University of Cincinnati, USA Introduction: Acute kidney injury (AKI), previously referred to as acute renal failure (ARF), represents an important problem in clinical medicine. Despite significant improvements in therapeutics, the mortality and morbidity associated with AKI remain high. The reasons for this include (a) an incomplete understanding of the underlying pathophysiologic mechanisms, and (b) the lack of early markers for AKI, and hence an unacceptable delay in initiating therapy. Fortunately, the application of innovative technologies such as proteomics to human and animal models of AKI has uncovered several novel proteins that are emerging as biomarkers and novel therapeutic targets. Methods: Literature review (PubMed, MedLine) from 2000 to the present. Results: Recent advances in proteomics have resulted in the identification of biomarkers in the plasma (NGAL) and urine (NGAL, KIM-1, IL-18) for the investigation of AKI, as well as identification of proteins that inform the pathophysiology of AKI and offer novel therapeutic targets. Conclusions: Proteomic studies will likely yield additional sensitive and specific biomarkers for the investigation of AKI resulting from diverse etiologies. Such tools will be indispensable for the early diagnosis and initiation of timely therapeutic measures. Goals and objectives: Primary FSGS is a leading cause of end stage renal disease (ESRD) in both children and adults, with loss of kidney function in 50% of patients over 10-years. The FSGS -CT was organized and implemented by the NIH in response to this poor prognosis, and the need to rigorously test treatment modalities and to delineate the cellular, molecular and genetic basis of this complex disorder. In evaluating the therapeutic interventions for the FSGS-CT, it was noted that no evidence based medicine has designated a specific therapeutic intervention for steroid-resistant FSGS that significantly reduces proteinuria or preserves renal function in a substantially large proportion of patients. However, the following 4 factors were taken into consideration in the ultimate design of this clinical trial:

& an established role for CSA in the treatment of FSGS & the potential, but unproven benefit, of intermittent high-dose corticosteroid therapy in combination with another immunosuppressive agent & the efficacy of either therapeutic intervention to induce sustained reduction in proteinuria after withdrawal of a therapeutic agent & the side effects and consequences of any long term therapeutic intervention, if withdrawal of medication is unsuccessful

The FSGS-CT is a Phase III randomized trial of patients greater than 2 years and < 40 years of age being conducted at over 100 participating sites in North America which are divided among 3 core networks with principal investigators, study coordinators, and a central data-coordinating center (http://fsgstrial.org). Eligibility criteria include: 1) an estimated GFR > 40 ml/min/1.73m2, 2) a first morning urine protein/creatinine ratio (Up/c) > 1.0, 3) biopsy-confirmed primary FSGS, 4) corticosteroid resistance as defined as failure to achieve sustained Up/c <1.0 based on a course of steroid treatment for 4 wks and/or a minimum cumulative dose of 56 mg/kg or 1,680 mg of prednisone or its equivalent. Major exclusion criteria include: 1) prior therapy with cyclosporine (CsA), tacrolimus, mycophenolate mofetil (MMF) or rapamycin, 2) BMI> 97th %tile for age or >40 kg/m2, 3) uncontrolled hypertension. Target sample size is 207 randomized patients to achieve 80% power to detect17.9% absolute difference in remission rate. Eligible patients are randomly assigned to one of two active treatment arms: CsA OR pulse dexamethasone and MMF. The target period for each therapeutic intervention is 12 months. Both study groups are also treated with either Lisinopril or Losartan for 18 months and low dose alternate day steroids for 6 months. The outcome measures have been defined to reflect clinical practice and to allow patients to be withdrawn if no therapeutic effect is evident within six months of randomization. The primary outcome is based on achievement of remission of proteinuria: complete remission (CR) Up/c < 0.2; partial remission (PR) Up/c < 50% of baseline value and < 1.0; or no remission (NR). The pattern of response to both therapeutic interventions will be assessed at 6, 12 and 18 months. Patients who do not achieve a CR or PR after 6 months of therapy in either therapeutic arm are defined as treatment failures for the primary outcome, and exit the study. For patients who achieve a CR or PR at six months, the primary outcome will be assessed again at 12 months. If patients have not maintained at least a PR at 12 months, they are considered a therapeutic failure and exit the study. The main secondary outcome is the persistence of remission following withdrawal of the CsA or MMF/dexamethasone after 12 months on therapy. This secondary outcome will be assessed after 6 months off therapy (i.e., 18 months after enrollment) only for patients who have achieved a CR or PR after 12 months on therapy.

Randomization began in November 2004 and ends on May 31st, 2008. 187 patients were enrolled and 136 randomized with 50 excluded for biopsy readings inconsistent with primary FSGS, Up/c <1.0, and eGFR <40 mL/min/1.73m2. Entry characteristics of the enrolled patients are: 57 < 24 years of age; 38% African Americans, 57% white, 5% other; 54% male, 46% female; eGFR 135 mL/min/ 1.73 m2 and Up/c >6.44. To date, 17 ancillary studies have been approved of which 11 received NIH support.

The FSGS-CT is the largest controlled trial of FSGS in North America and will establish a standard of therapy for corticosteroidresistant primary FSGS. Additional benefits of the trial are the establishment of an infrastructure for the study of FSGS, the creation of a national repository of biospecimens for investigations on the pathogenesis of FSGS and the role of histological subclassifications of FSGS in the response to therapies, and the evaluation of the efficacy of withdrawing immunosuppressive drugs while maintaining ACE inhibitors/ARBs. A logical extension of the trial is the development of a Pediatric Nephrology Clinical Trials Group to facilitate new investigations, innovations and faculty development in translational research.

Department of Pediatrics, Kyorin University School of Medicine, Japan Introduction: Nephrotic syndrome (NS) is a common kidney disorder with multiple etiologies. The mechanisms by which therapeutic agents induce remission in susceptible individuals with NS are not well understood and remain one of the most important questions in nephrology today. We previously demonstrated that glucocorticoid receptor and glucocorticoid inactivating enzyme, 11 hydroxysteroid dehydrogenase type 2, are expressed in the glomerular podocyte (Kidney Int 1999; J Clin Endocrinol Metab 2002) . Recent compelling evidence indicates that therapeutic agents may exert the antiproteinuric effect by restoring nephrin biogenesis because the loss of nephrin expression and altered cellular localization of nephrin in the podocyte foot processes results in proteinuria. Method: To gain a direct crosstalk between therapeutic agents action and altered nephrin biogenesis, we focused on the role of the intracellular energy homeostasis in maintaining nephrin trafficking machinery. To inhibit nephrin biogenesis, we established a model of the endoplasmic reticulum stress (ER) induced by glucose starvation in nephrin expressing cell line. Result and Discussion: Glucose starvation induced hypoglycosylated nephrin which retained in the ER, not be transported to the plasma membrane. Interestingly glucocorticoid partially rescued plasma membrane localization of nephrin through recovery of ER chaperone (calreticulin) function via increase of ATP by upregulation of the mitochondrial genes (Kidney Int 2006) . On the other hand, mizoribine, which was discovered in Japan and frequently used for steroid dependent NS, restored the intracellular energy balance by salvaging the ATP levels and completely rescued expression of the mature, fully-glycosylated, plasma membrane nephrin by a mechanism dependent on the inhibition of the Inosine 5'-monophosphate dehydrogenase activity (J Am Soc Nephrol 2007). We also determined that the energy imbalance alters not only nephrin biogenesis but also other N-glycoprotein 1-integrin biogenesis. These data suggest that immunosuppressants may directly act on the diseased podocyte through interacting with energy system, results in the rescue of pathological proteinuria of NS.

Division of Child Health and Development, Department of Pediatrics, Kobe University Graduate School of Medicine, Japan Introduction: Children with frequent-relapsing nephrotic syndrome (FRNS) experience the serious side effects that result from continuous corticosteroid therapy. In Japan, most of the pediatric nephrologists treat children with FRNS with cyclophosphamide, mizoribine or cyclosporine (CyA). And more than half of children with FRNS are treated with CyA. CyA is a relatively new agent that is useful in the management of FRNS. The beneficial effects of CyA, however, often are accompanied by side effects. Of greatest concern is chronic CyA nephropathy, characterized by arteriolar lesions and tubulointerstitial (TI) lesions. Methods: We examined clinical course of chronic CyA nephropathy and risk factors for the development of CyA-induced TI lesions. We conducted a prospective, open-label multi-center randomized controlled trial with trough level monitoring of CyA (Sandimmune) to develop a safe and effective CyA treatment for FRNS. Patients were randomly divided into two groups with both initially receiving CyA for 6 months to maintain a whole-blood trough level between 80 and 100 ng/ml. Over the next 18 months, the dose was adjusted to maintain a slightly lower (60-80 ng/ml) trough level in Group A, while Group B received a fixed dose of 2.5 mg/kg/day. The primary end point was the rate of sustained remission with analysis based on the intention-to-treat principle. Results: The arteriolar lesions were improved by discontinuation of CyA, but the TI lesions did not regress with drug discontinuation (J Am Soc Nephrol 11:2265 -2271 , 2000 , Pediatr Nephrol 16:723-727, 2001 . Thus, prevention of the development of CyA-induced TI lesions is the most important issue in CyA treatment for children with FRNS. Duration of CyA treatment (>24 months) and duration of heavy proteinuria (>30 days) were independent significant risk factors for the development of CyA-induced TI lesions (Kidney Int 61:1801 -1805 , 2002 . After 2 years, the rate of sustained remission was significantly higher in Group A as compared with Group B. Mild arteriolar hyalinosis of the kidney was more frequently seen in Group A than in Group B, but no patient was diagnosed with CyA-induced TI lesions. Conclusions: CyA for 2 years in a dosage that maintains the trough level between 80 and 100 ng/ml for the first 6 months and 60 and 80 ng/ml for the next 18 months is an effective and relatively safe treatment for children with FRNS (Kidney Int 73: 1167 -1173 . I also introduce an on-going prospective multi-center randomized controlled trial with C2 monitoring of CyA (Neoral) (JSKDC 03).

SYM-9-1: RENAL TUBULAR ACIDOSIS.

Professor of Pediatrics, University of Vermont; Director of Research, The Barbara Bush Children's Hospital, Maine Medical Center, Portland, Maine, USA.

Background: The inability of lowering urinary pH to less than 5.5 and raising net acid excretion to normal concentrations in response to metabolic acidosis are cardinal features of type 1 renal tubular acidosis (RTA). The bicarbonate wasting from the proximal tubules characterize type 2 RTA. Aldosterone deficiency or resistance gives rise to type 4 RTA. Clinical features: The case vignettes of 4 children with RTA illustrate the diverse clinical presentations, the consequences of missed diagnosis, non-compliance and treatment. Guidelines for diagnostic workup of RTA types 1, 2 and 4 follow.

The key experiments on the mechanisms of growth failure in metabolic acidosis are reviewed: impaired growth hormone pulsatile secretions, altered IGF-1 expressions, reduced nutritional intakes.

Major studies on clinical associations and genetic loci are presented.

Recommendations: This review ends with the author's recommendations on therapeutic strategy in overcoming non-compliance.

Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Dent disease is an X-linked renal tubular disorder characterized by low molecular weight (LMW) proteinuria, hypercalciuria, nephrocalcinosis and progressive renal failure. Patients usually go into end-stage renal failure when they are 49 years old in average. Most of the patients are detected as proteinuria by a school urinalysis screening in Japan. About 60% of the Japanese patients with Dent disease are due to the mutations in chloride channel 5 (ClC-5) gene (CLCN5). CLCN5 encodes a 746 amino acid ClC-5 that has about 12 transmembrane domains. Mutational analysis of CLCN5 revealed mutational "hot spots" at codons 279, 648, and 704 (nonsense mutations) and at codon 506 (missense mutation) in British and Japanese patients. Three missense mutations (S270R, L278F and R280P) on the putative loop between domains 5 and 6 of ClC-5 protein suggest that this putative loop may have a regulatory role in ClC-5 function. ClC-5 protein is expressed in the proximal tubule, thick ascending limb of Henle, and the intercalated cells of the collecting duct. ClC-5 protein is localized to the subapical endosomes with H + -ATPase in the proximal tubule. Acidic endosomal pH formed by ClC-5 and H+-ATPase is necessary for normal endosomal function, including endocytosis, trafficking, and recycling to the surface. Two knocked-out mouse models revealed that megalin's expression was reduced. Moreover, histological analysis of the kidney specimen from the patient revealed reduced expression of megalin on the luminal membrane of the proximal tubules. Urine concentration of megalin is decreased in the patients with Dent disease. These observations suggest defective binding of protein with megalin in the luminal membrane of the proximal tubule and resulted proteinuria. Approximately 10% of patients with Dent disease have OCRL1 (causative gene for Lowe syndrome) mutations. OCRL1 encodes a protein that regulates the function of endosome. Mutations in OCRL1 can occur with isolated renal phenotype of Dent disease in patients lacking cataracts, renal tubular acidosis, and neurological abnormalities that are characteristic of Lowe syndrome. However, the precise pathogenesis is still unknown. This also suggests genetic heterogeneity in the pathogenesis of Dent disease. Unlike the patients with typical Lowe syndrome, none of patients have metabolic acidosis. These observations and findings suggest that OCRL1 mutations can cause the isolated renal phenotype of Dent disease and affected individuals lack the cataracts, typical facial features, renal tubular acidosis, and neurologic abnormalities that are characteristic to Lowe syndrome. It is difficult to explain that OCRL1 mutations can cause the isolated renal phenotype of Dent disease. However, it is possible that another phosphatase, INPP5B, which shares amino acid homology with OCRL1, can compensate phosphatase activity in patients with Dent disease due to OCRL1 mutations.

There are no specific interventions at present that will change the natural course of renal manifestations and progressive renal failure in patients with Dent disease. Hypercalciuria is dysfunction corrected by thiazide diuretics therapy in doses similar to effective doses for idiopathic hypercalciuria, presumably by stimulating the reabsorption of calcium in the distal convoluted tubule, where ClC-5 channel is not expressed. However, this is not a long-term study which provides the evidence that it is effective to prevent or delay the progression of end stage renal failure. In animal experiment using clcn5 (mouse chloride channel 5 gene) knock-out mice, high citrate diets can delay the progression of nephrocalcinosis and end stage renal failure. Treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker may delay progression of end stage renal failure. The kidney plays a pivotal role in elimination of the toxic compounds, e.g. endogenous metabolites, drugs, environmental compounds, and their metabolites from the body. Elimination of these toxic compounds via kidney is performed not only by glomerular filtration but also tubular secretion. Over the last decade, tremendous knowledge on the role of organic anion transporters in tubular secretion has been clarified. The organic anion transporters include several families; namely, OAT family, OATP family and MRP family. Among these, the members of OAT family play the central in the kidney.

In the kidney, OAT1 and OAT3 are expressed in the basolateral membrane of the proximal tubular cells, and take up a variety of drugs and their metabolites from the blood. In the brain, oat3 is expressed in the blood-brain barrier and blood-spinal fluid barrier, and play a role as a "functional BBB or BBBCF". These OAT members transportlactam antibiotics, diuretics, NSAIDs, ACEIs, ARBs, methotrexate and so on. OAT members also transport endogenous compounds, such as cyclic AMP and GMP, prostaglandins and dicarboxylates.

OAT family includes two members, each of which transports important endogenous compound, e.g., urate and carnitine. hURAT1 (human uric acid transporter 1) was identified as the fifth member of OAT family and was revealed to transport urate. hURAT is located in brush border membrane of proximal tubular cells and take up urate from glomerular filtrate. Mutations in hURAT1 gene cause "hereditary renal hypouricemia". OCTN2 (CT1) is a carnitine transporter expressed ubiquitously in various tissues. Carnitine is an essential compound in the -oxydation of fatty acids, and genetic defects in OCTN2 gene causes a "systemic carnitine deficiency".

In my talk, I would like emphasize significance of OAT family in its physiological, pharmacological and pathophysiological aspects. The registry of the North American Pediatric Renal Trials and Collaborative Studies (formerly the North American Pediatric Renal Transplant Cooperative Study) was initiated in 1987 to capture information about current transplant practice and trends in immunosuppressive therapy with a goal of improving the care of the pediatric renal allograft recipient in North America. Over the past two decades, data has been collected from 10,762 transplants (9,854 index) in recipients <21 years and has revealed substantial changes in patient management and outcome with time. Whereas the percentage of young (<6 years) recipients has remained constant at 20%, the percentage of young (<10 years) deceased donors has decreased from 35% in 1987 to only 7% in 2007. The height SDS at the time of transplant has increased from -2.43 to -1.37 and the mean number of hospitalization days during the first transplant month has decreased by 50%. Substantial changes in induction and maintenance immunosuppressive therapy have been associated with a decreased probability of a first rejection by 12 months for living-donor (54.1% to 13.7%) and deceased-donor (69.3% to 17.9%) recipients. In addition, 1 year graft survival rates have improved from 89.4% and 75.2% for living-donor and deceased-donor recipients, respectively in 1987-1990, to current rates of 95.7% and 95.0%. This improvement has, however, been complicated by a malignancy rate that has increased from 1.05 in 1987-1990 to 2.45 more recently. Nevertheless, 5 year patient survival has significantly improved for all deceased-donor recipients and the 3 year survival of infants receiving living-donor grafts has improved from 89.8% to 95.5%. Ongoing data collection in the transplant registry and the continued development of prospective clinical trials based on the analysis of registry data will likely result in continued improvement in the outcome of pediatric transplant recipients.

Department of Pediatrics and Pediatric Nephrology, Tokyo Metropolitan Children's Hospital, Japan

We have two registries regarding renal transplantations in children: Japanese National Pediatric ESRD Registry and Japanese Kidney Transplantation Registry. I would like to introduce the recent data from these registries in this paper.

In Japan, 50 to 60 new patients younger than 15 years old became ESRD every year. In 402 children who became ESRD from 1998 to 2004, 83% were introduced to PD, 9% were introduced to HD and 9% received pre-emptive transplantation. The frequency of pre-emptive transplantation was a small number(s ), but it has recently increased up to 22% in 2004. Sixty five percent of all ESRD received transplantation within 5 years after becoming ESRD.

A total of 2,031 children younger than 20 years old received transplantations from 1964 to 2004 in Japan. Of all, only 9.4% received cadaveric transplantation. 1,124 patients were younger than 15 years old and 132 patients were younger than 5 years old. After 2000, the number of the patients who received transplantation increased from 60/year up to about 90/year. We investigated patients and graft survivals in 1,751 children whose outcomes can be traced. We divided the patients into 3 groups: 440 children in 1964-1985, 646 patients in 1986-1995, 413 patients in 1996-2001 . Patients survival rate in 5 years improved from 82% to 96% and 98%, and graft survivals improved from 63% to 78% and 90% in each 3 groups, respectively. Ten years graft survivals changed from 48% to 66% after 1985. Five years graft survivals in the group of 1996-2001 were 93% in 1-5 years old, 91% in 6-12 years old and 89% in 13-19 years old. These results showed the excellent data.

In addition to the data from the registries, I showed the data in our hospital (TMCH) as to graft survival in patients with ABO incompatibility and FSGS. Their survivals were not different from those of other transplant children in TMCH.

Department of Nephrourology, Gt Ormond St Hospital for Children NHS Trust, UK Studies of outcome post renal transplant over 20 years are now beginning to emerge. Such information is of considerable importance in order to counsel patients and families.

The overall mortality rate remains high, with a relative risk of death post transplant that is 12.7 times higher than that of the age-related normal population, with little sign of improvement since the 1980s. Young age at transplant is an important factor that has been demonstrated to affect patient survival, although there is evidence that its effect has declined in recent years. All reports show a small but consistent benefit of living donation (LD).

The major causes of death post transplant are cardiovascular disease (CVD), infection and malignancy, variously reported as 30-36% for CVD, 24-56% for infection and 11-20% for malignancy. Two other important factors that contribute to death are nonconcordance with medications or treatment withdrawal and obesity. All studies show a survival advantage for patients who are transplanted in comparison to dialysis. It might be expected, therefore, that patient survival after pre-emptive transplant would be superior, and studies have shown this to be the case.

Transplant survival has shown a steady improvement over the years. It used to be that young recipient and donor age adversely affected outcome, but in the last decade, this no longer seems to be so. Adolescents, however, have the worst transplant survival of all ages, mainly due to non-concordance. LD and preemptive transplantation and changes in immunosuppression to more powerful agents also benefit outcome.

Other causes of transplant loss The incidence of diabetes has been increasing post transplant, and is associated with increased graft loss. Diseases that recur post transplant include FSGS, MPGN and HUS. Oxalate will continue to be deposited in the transplanted kidney if liver transplant is not undertaken in patients with hyperoxaluria. Nephrotic syndrome can recur in patients with congenital nephrotic syndrome, and anti-GBM nephritis in patients with Alport's syndrome, both due to the development of antibody to the 'missing' protein. Hypertension is very common and is a significant and independent predictor of poor long-term transplant function,

Final height is improving, but so is obesity. Despite a high retransplantation rate and the presence of significant morbidity, renal transplantation in children can lead to attainment of a productive and satisfying life, with a high degree of rehabilitation in adulthood. In Thailand SLE is not an uncommon disease. The ratio of pediatric SLE to pediatric out-patients in tertiary care hospitals is 1: 700. The Thai Pediatric Nephrology Association has conducted a multicenter study in 13 tertiary care hospitals all over the country. The objective of the study is to determine the clinical outcomes of Thai children with SLE and risk factors for chronic renal insufficiency.The data of 500 SLE children, age at diagnosis less than 15 years, newly diagnosed during 1 January 2002-31 December 2006 were reviewed. Severity and damage of the disease were assessed using ECLAM index and SLICC/ACR damage index respectively. The ratio of female: male is 5.5: 1. Kidney involvement is found in 82% of the patients. Kidney biopsy is done in 351 patients. The most common pathology found is diffused proliferative lupus nephritis. Prednisolone plus pulse intravenous cyclophosphamide is the standard treatment for these patients. There has been increasing use of mycophenolate mofetil in recent years. Majority of patients achieve favorable outcome. The mean ECLAM index at initial is 6 + 2.7 and decreases significantly after treatment. Chronic renal insufficiency is found in 11 patients while 7 of these patients require renal replacement therapy. Risk factor for developing chronic renal failure is initial GFR < 60 ml/min/1.73 m2. Concernig complication and damage, the frequently found organ damages are eyes (22.5%), kidney (10.5%), neurologic (8.5%) and musculoskeletal (16%) systems respectively. In this study, 14 patients died and the most common cause of death is infection. Quality of life which is one of the important outcome measures is being studied to determine the quality of life of Thai children with SLE. Introduction: Primary IgA nephropathy is the most common primary renal disease in the world wide. Since it was reported in 1968 by J Berger and N Hinglais, the disease of IgA nephropathy is emphasized more and more in the aspect of incidence, clinical characters, prognosis and treatment. To understand the incidence as well as the clinical features in IgA nephropathy a retrospective study on IgA nephropathy was finished and reported by the Chinese Society of Pediatric Nephrology in 2007, the relevant data was compared with that reported previously by other groups. Method: Totally 1349 cases of IgA nephropathy from 33 hospitals of different cities from January 1995 to December 2004 were collected and analyzed retrospectively. More data on childhood IgA nephropathy from published reports in Chinese along with data from other countries were compared. Result: IgA nephropathy in children under 14 years accounted for 1.37% of the hospitalized cases with urological-kidney diseases, and 11.18% of cases with renal biopsies. The cases of IgA nephropathy increased from 327 (0.83%) to 1022 (1.73%) in the periods of 1995 to 1999 and 2000 to 2004, respectively (P<0.01). Whereas, the previous survey conducted by the Chinese Society of Pediatric Nephrology demonstrated that IgA nephropathy accounted for 7.3% of cases with renal biopsies, and ranked forth in the renal diseases in children.

The proportion of IgA nephropathy in renal dieases or in cases with renal biopsies seemed increased in recent years in China, which might attribute to the improvement of knowledge on renal diseases including IgA nephropathy, the increased case numbers performed renal biopsy and more available medical resources to take care patients. Nevertheless the real incidence of IgA nephropathy still need to carry out epidemiology investigation. The global epidemic of obesity is largely responsible for the high prevalence of metabolic syndrome, which is characterized by central obesity, hypertension, dyslipidemia, insulin resistance, and elevated proinflammatory biomarkers. Metabolic syndrome adversely affects kidney structure and function. Increased body mass index has been shown to be associated with increased risk for developing end-stage renal disease. The mechanism by which obesity leads to renal disease is not fully understood at the present time. This presentation will summarize some human and animal studies conducted in the United States and Asian countries on the subject of obesity and related kidney disease. Obese patients have glomerular hyperfiltration and are at higher risk for developing glomerulopathy and focal segmental glomerulosclerosis. Investigations on adipokines, which include leptin, resistin and adiponectin, demonstrate an important role of adipokines in the pathogenesis of obesity-related renal disease. In children with chronic renal disease the level of a cardiovascular protective factor adiponectin is relatively low in overweight patients as compared to lean patients. An inverse correlation between albuminuria and plasma levels of adiponectin has also been shown in non-diabetic adults with obesity. Transgenic mice lacking adiponectin (Ad-/-mice) exhibit an increased urinary albumin excretion and effacement of podocyte foot processes. Treatment of adiponectin to the Ad-/-mice reduces albuminuria and restores podocyte morphology. The effect of adiponectin is largely due to the activation of 5'-AMP activated protein kinase (AMPK). Since albuminuria is a strong predictive factor for renal disease progression, adiponectin and its signal transduction pathway may represent a therapeutic target for potential treatment of obesity-related kidney disease. Introduction: The uncontrolled hyperglycemia of maternal diabetes has been found to negatively affect pregnancy, including renal agesis, small kidney, hydronephrosis and fused kidneys. Furthermore, the number of nephrons was significantly reduced in the pups of diabetic female rats. We hypothesized that children of gestational hyperglycemic mothers develop defects of renal development similar to those observed in our animal model. Methods: We observed the defects of renal development of diabetic pregnancy from late phase of embryogenesis to postnatal period in animal model (C57BL/6J mice). We also used 2-(2-D) and 3-(3-D) dimensional power Doppler renal ultrasound (US) to measure and compare the kidney/liver echogenic ratio in 76 children born to gestational hyperglycemic mothers versus 240 age-matched healthy children. The age of 20 babies was < 6 months throughout their follow-up, while 56 children were followed between 6 months and 4 years of age. Whole kidney volume, mean grayness (MG) and vascularization (VI), flow (FI) and vascularization-flow (VFI) indices were calculated. Result: In our preliminary studies, defects and abnormalities of mice fetal kidney development under the environment of maternal hyperglycemia induced by streptozotocin injection were established. Histologically, large glomerular size, reudced nephron number, and ureteric tubular detachment were observed. Cell apoptosis, but not cell proliferation, was significant increased in fetal kidney of diabetic group. In the molecular level, we noticed that glial cell line-derived neurotrophic factor (GDNF) and early growth response alpha (EGFα) expressions are down-regulated at peri-tubular region of developing fetal kidney of diabetic group. In > 6-month-old children from hyperglycemic mothers during pregnancy, the 2-D US echogenic kidney/liver ratio was higher than in age-matched controls (P<0.01). Furthermore, higher incidence of non-obstructive hydronephrosis was detected in 20 children (26.3%) born to gestational hyperglycemic mothers then no-hyperglycemic mothers (1%). 3-D US demonstrated lower mean renal volume, VI, FI and VFI in children of hyperglyce-mic mother then in children of normoglycemia mothers beyond six months of age. Conclusion: GDNF-dependent activation of GFRα-1 and Ret in fetal renal tissue is mediated by a complex intracellular signal network. The kidney/liver echogenic ratio on 2-D US and indices of renal volume and vascularization on 3-D power Doppler scan may enable clinicians to establish an early baseline and follow the evolution of these renal characteristics in high-risk children.

Paediatric Nephrology Center, Princess Margaret Hospital, Hong Kong, SAR, China

Children who reach chronic kidney disease (CKD) stage 4 (GFR < 30 ml/min/1.73 m2) should receive education about kidney failure and options for its treatment, including peritoneal dialysis (PD), hemodialysis (HD) and renal transplantation1. A systemic plan of monitoring basing upon the combination of clinical, biochemical, and psychosocial assessment prior to dialysis initiation is required. Dialysis initiation should be considered when GFR is 9 to 14 ml/min/ 1.73 m2 (CKD stage 5) or at greater GFR levels in the presence of malnutrition, fluid overload, hypertension, hyperkalaemia, growth failure or neurological consequences of uremia1.

While renal transplantation remains the optimal therapy for children with end-stage renal disease (ESRD), the majority of children require maintenance dialysis because of lack of a suitable donor. The choice of dialysis modality has to take into account of patient size with difficulties of vascular access in small children, patient/family choice, medical co-morbidities, and family support 1,.2. PD is usually the favored modality of pediatric renal replacement therapy (RRT) especially for young children. While PD continues to be the most prevalent modality selection for all children in some countries, there has been increase in HD utilization in the last decade in the United States. The utilization of PD in pediatric patients is approximately 50% worldwide 3. In the United States, PD is the most frequent dialysis modality (60% of dialysis children) according to the NAPRTCS Registry, whereas HD is more common according to the USRDS data which reflects that there is a preference for HD for adolescents patients that are cared in adult dialysis unit (4) . Contraindications to PD include omphalocele/gastrochisis, bladder extrophy, diaphragmatic hernia and lack of an appropriate care giver. Contraindications to HD include very small infants, lack of vascular access, contraindications to anticoagulation and cardiovascular instability 5.

Automated PD (APD) is the most frequently used and advocated PD modality in children as it gives greater freedom to the children and caregivers during the day for school and social activities5. However, continuous ambulatory PD (CAPD) is commonly used in countries that lack finances and technical support4.

There is recent advancement in automatic cyclers with computer chips that provide recording of treatment provision and remote access that resulted in improved patient adherence 6. The peritoneal dialysis adequacy recommendation has recently been changed due to reanalysis of the CANUSA data which showed residual renal function is the most important predictor for patient mortality and in the ADEMEX trail that increasing peritoneal small solute clearances did not lead to improved PD patient survival 6. The recent recommended minimal "delivered" dose of total (peritoneal and kidney) small-solute clearance should be a Kt/V urea of at least 1.8/wk 1.

Many children have long-term dependence on a functioning peritoneal membrane due to long waiting time for renal transplant in some countries. The use of biocompatible new PD solutions such as Physioneal (lacatate/ bicarbonate mixed buffer pH 7-7.4), Extraneal (7.5% icodextrin), Nutrineal (1.1% amino-acid) not only preserve the peritoneal membrane but also increases the possibility of tailoring the APD prescription to the clinical, metabolic and nutritional needs of children and adolescents 7

During the past two decades, children have benefited from major improvements in both technology and clinical management of HD. Newer machines provide more precise control of ultrafiltration by volumetric assessment and continuous blood volume monitoring. More biocompatible synthetic membranes and specific small size material dialyzers and tubing make it possible to put infants on HD. However, the provision of adequate vascular access remains the greatest obstacle to successful HD, especially in infants 8. HD usually requires 4-h thrice-weekly in-hospital treatment sessions. Home nocturnal HD in adult studies reveals improved biochemical control and reported health-related quality of life. Frequent home HD can be provided by installing a water treatment system in the patient's home, or with machines that use sterile dialysate in bags (NxStage systems) 6,.9. Preliminary experience with frequent HD show that it leads to improved growth, decreased fluid and dietary restriction, excellent metabolic and blood pressure control, and the lack of need for phosphate binders. 10

Renal transplantation is the goal for children with ESRD. However, the chronic immunosuppression exposes children to multiple complications and drugs side effects. With the newer generation of powerful induction and maintenance immunosuppressants, immunosuppression minimization is a realistic objective for the pediatric patients which reduces morbidity from the toxicities associated with immunosuppressive drugs. Steroid minimization and avoidance have shown early promise. Elimination of Calcineurin-Inhibitors (CNI) carries the potential to minimize the chronic graft 'non-immune' injury which is one of the main causes of chronic allograft nephropathy (CAN), one of the leading cause of transplant kidney loss 11.,12. Randomized, prospective studies of steroid and CNI minimization and /or avoidance are needed to clearly confirm their short and long term safety and efficacy.

1. National Kidney Foundation.KDOQI clinical practice guidelines for peritoneal dialysis adequacy:update 2006. Am J Kidney Dis: S99-S175. 2. Watson AR, Gartland G. on behalf of the European Paediatric Peritoneal Working Group. Guidelines by an AD HOC European

Nephrotic syndrome (NS) is a common kidney problem among hospitalized pediatric patients. Basic pathology is related to leaking of proteins through glomerulus. Abnormality of immunoglubulins occurs because of gloumerular leakage, decrease synthesis and abnormal metabolism. Immunoglobulin is lost in urine along with albumin leading to hypogammaglobulinaemia. Deposition of IgM in the kidney is associated with longtime prognosis. Nephrotic syndromes (NS) with atopic child are associated with raised level of immunoglobulin E. Deceased level with reduced functional capacity of immunoglobulin is responsible for increase prone to infection in already immunocompromised patients with nephrotic syndrome. Low IgA level in patient with NS is associated with respiratory tract infection and diarrhea, and are frequently relapser. Studies showed that significantly reduced level of IgG is found in steroid resistant nephrotic syndrome in compare to steroid sensitive nephrotic syndrome. Persistent low or low normal serum IgG level during period of remission is predictor of frequent relapse in children with idiopathic nephrotic syndrome. So, immunuglobulins play an important role in the pathogenesis, in the management plan, and as a predictor of the outcome of nephrotic syndrome. Introduction: Steroid-resistant nephrotic syndrome (SRNS) with focal and segmental glomerulosclerosis (FSGS) is a heterogeneous disorder and the most severe and frequent type of all glomerulopathies in children leading to end stage renal failure. The podocyte is at the centre of development and progress of FSGS since this unique cell type plays a major role in the integrity of glomerular structure and permeability. Results: The rate of complete remission of SRNS after induction therapy using different immunosuppressive agents is reported to range between 30-84%, depending on the treatment schedule and on the underlying defects of FSGS. Children with genetic types of FSGS barely respond to immunosuppressive therapies and overtreatment prior to transplantation should be avoided. The response of children with an idiopathic type of FSGS to immunosuppressants is superior to those with genetic FSGS. However, many children with idiopathic FSGS do not enter complete remission if they are undertreated, e.g. by short term immunosuppressive monotherapies. If immunosuppressive treatment fails, these patients will have to undergo renal transplantation. However, as the unknown pathogenetic mechanisms may persist, more than one third of these patients with idiopathic FSGS develop a rapid recurrence of SRNS responding poorly to further long term therapeutic attempts. Conclusion: The aim of this review is to show that, by contrast with previously published data, new treatment options taking into account recently identified genetic etiologies of SRNS, and in idiopathic forms superior results of an intensified treatment mode, currently lead to a different, more effective approach of childhood SRNS with lesions of FSGS.

Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand Advances in the treatment of Beta-Thalassaemia including ironchelating agents and Hematopoietic stem cell transplantation (HSCT) make long term outcome of these patients much more important. Despite being one of the most common hereditary hemoglobinopathies in many parts of the world, data on long term renal involvement in Beta-Thalassaemia were scant. Glomerular filtration is usually normal but recent studies showed that proximal tubular dysfunction is common in patients with Beta-Thalassaemia. This was demonstrated by uricosuria, aminoaciduria, low urine osmolality, increased urine levels of low molecular weight protein, N-Acetyl-Beta-D-glucosaminidase (NAG) and Beta2-microglobulin. Urine NAG, a sensitive marker for proximal tubular damage, was found to be correlated with proteinuria, patient's age, serum ferritin, duration of deferoxamine, and duration of receiving blood transfusion. The causes of tubular abnormalities are most likely chronic anemia and oxidation reaction from iron deposition as increased level of urine malondialdehyde, an indicator of lipid peroxidation, was also reported.

Although rarely resulting in clinical disorders that warrant treatment, prolonged repeated tubular damage may cause tubulointerstitial fibrosis and chronic kidney disease. These patients may also be more at risk of acute renal failure from hypovolemia and nephrotoxic substances. Acute and chronic kidney diseases were reported in children and adult receiving HSCT but our long term study in a small group of Beta-Thalassaemia patients post HSCT showed low incidence of chronic kidney disease and a better renal tubular parameters than children of the same age and disease severity but without HSCT.

Peking University First Hospital, Beijing, PR China Introduction: Alport syndrome is a hereditary glomerulonephritis caused by COL4A3, COL4A4 and COL4A5 gene mutations. It is manifested by hematuria, sensorineural hearing loss, ocular lesions and progressive renal failure. In order to understand the disease via clinical aspect and genetic aspect, a retrospective study was carried out based on data from Chinese Alport syndrome patients. Method: Clinical data including manifestations, renal pathology, type IV collagen alpha chains staining, cochlear and ocular abnormalities were collected and analyzed. PCR amplification of mRNA or genomic DNA of (IV) chains was applied to detect mutations. COL4A gene mutations were confirmed by DNA sequencing. Data or parameters obtained from this study were compared to others published previously by other investigators based on Caucasian population. Result: There were 146 un-related index cases of Alport syndrome enrolled in this study, which included 104 males and 42 females. Among them, 134 patients were diagnosed with X-linked Alport syndrome and 12 patients (8.2%) with autosomal recessive Alport syndrome. No autosomal dominant hereditary mode of Alport syndrome was identified. Almost half patients (58%) presented with hematuria as the onset symptom, the rest part of patients (42%) presented with hematuria and proteinuria at the onset of the disease. Around 20% of patients manifested with nephrotic proteinuria. Non-glomerular hematuria was reported in about 20% of Alport patients. It seemed that 17% of patients was de novel mutation of COL4A5. There were 48% of Alport patients with hearing loss and 57% of patients with ocular lesions. One confirmed X-linked Alport syndrome patient was also diagnosed with IgA nephropathy. Mutation analysis revealed that, in this study, 51% of X-linked Alport syndrome patients with point-mutation and, only 4% of patients with large deletion in COL4A5 gene. Conclusion: The clinical features revealed in this study in Chinese patients were similar to the previous reports, in addition to the prompt that higher portion of patients with proteinuria at the disease onset and small portion of patients with non-glomerular hematuria. While large deletion of COL4A5 gene was less than the other reports. annual report). This study was done to identify pediatric renal transplant patients with high risk for allograft thrombosis and develop a risk stratification protocol for post-operative anticoagulation. Method: We screened every patient at the pretransplant evaluation for thrombophilic risk factors including Antithrombin III, Protein C or Protein S deficiency, Activated Protein C resistance, Factor V Leiden, MTHFR or Prothrombin gene mutation, Hyperhomocysteinemia, High Factor VIII, high Lipoprotein (a), Dysfibrinogenemia, and Antiphospholipid Antibodies. The patients were assigned a risk category (Level I-IV) based on the presence of thrombophilic risk factors. Their postoperative anticoagulation plan was pre-determined based on their risk level [table1]. Heparin drip was initiated a few hours after the transplant and titrated to achieve a 1.5 fold aPTT level. Anticoagulation was changed to low molecular weight heparin (LMWH) on day 2-4, when the risk of major bleed was over, and serum creatinine had normalized. Result: Ten patients (aged 2-17 years) have been screened and 8/10 were found to be at high risk for thrombosis (3 were in Level II or 5 were in level III). The thrombophilic factors (number of patients) identified were prothrombin gene mutation (2), MTHFR (8), Lupus anticoagulant (2) and low protein S (2). Six patients have undergone renal transplant. All were successfully treated with LMWH postoperatively. No patient has developed allograft thrombosis. 1/5 patients developed a peri-renal hematoma requiring evacuation 7 days after the surgery, but completed prophylactic LMWH therapy. Conclusion: Thrombophilia is markedly common in pediatric kidney transplant recipients. Universal screening can stratify risk and allow an effective intervention to reduce that risk. Our Institution has developed a unique risk stratification protocol to identify patients at high risk for allograft thrombosis and prevent this complication by post-operative anticoagulation. However; larger scales, prospective randomized control trial using this protocol are needed. Introduction: Peritoneal dialysis (PD) is the major form of dialysis in use for infants and children with chronic renal failure (CRF). We evaluated the current status of children on PD in Korea. Method: In May 2008, questionnaires were sent to the pediatric nephrologists via e-mail. The questionnaires were about epidemiology, PD modes and adequacy, growth, blood pressure, laboratory findings and medications. Four centers replied and those data were reviewed. Result: A total of 103 patients were included in this study. Male to female ratio was 1.6:1. Mean age was 11.5 ± 4.9 years (0~19 years). Primary renal diseases diagnosed were as follows: primary glomerular disease (34%), chronic pyelonephritis-reflux nephropathy (14.6%), systemic disease (9.7%), renal dysplasiahypoplasia (8.7%), heredofamilial disease (6.8%), vascular disease (3.9%), drug-induced nephropathy (1.0%), and unknown (12.6%). PD modalities were as follows: CAPD (42.7%), CCPD (27.2%), NIPD (11.7%), and Hybrid (18.5%). Weekly Kt/V was 2.1±2.0 (0.3~4.1). Results of peritoneal equilibrium test (PET) were as follows: low 36.8%, low average 31.6%, high average 19.7%, and high 11.8%. Z-score for weight was -1.00±1.20 (-4.54~2.50). Zscore for height was -1.55±1.65 (-9.42~1.87). Growth hormone was administered in 24.3% of patients. Systolic blood pressure (BP) for their ages and heights was as follows: < 50 percentile 27.2%, 50~90 percentile 33.0%, 90~99 percentile 10.7%, and > 99 percentile 13.6%. Anti-hypertensive drugs were administered in 62.1% of patients. Laboratory findings were as follows: hemoglobin 10.5±1.4 g/dL, calcium 9.7± 0.7 mg/dL, phosphorus 5.4± 1.4 mg/dL, parathyroid hormone 324.2±342.8 pg/ml. Conclusion: Primary glomerular disease was the most common cause of CRF. CAPD was the most prevalent PD modality. Dialysis doses were variable. Low and low average peritoneal transport type were common. Growth disturbance were noted in many patients. Some patients had hypertension even with antihypertensive drugs. Hemoglobin level was slightly low. Calciumphosphorus levels were maintained adequately, but many patients had secondary hyperparathyroidism. Introduction: Peritonitis remains one of the major complications of peritoneal dialysis (PD) despite advances in Tenckhoff (TK) catheter design and dialysis techniques. This study examined factors associated with peritonitis and TK outcomes in children with end-stage renal disease (ESRD) over the past two decades. Method: All TK catheter insertions performed in 78 paediatric patients with ESRD (median age at diagnosis at end-stage renal failure of 12.2 years, range 0.07-20 years) between December 1985 to May 2007 were reviewed retrospectively. Peritonitis rate was calculated as number of episodes/patient-year. Kaplan-Meier survival analysis was done using the log-rank test. Poor outcome was defined as catheter failure and removal. Factors associated with peritonitis studied include age at TK insertion, coiled vs straight catheters and exit site infection. Multivariate logistic regression analysis was used to determine correlations.

Result: A total of 124 TK insertions were performed in 291 patientyears. The incidence of peritonitis decreased from 1.2 episodes/ patient-year in 1997 to 0.29 episodes/patient-year in 2006. Staphylococcus aureus was the most common isolated organism (19.2%) followed by coagulase-negative Staphylococci (9.6%), Enterobacter cloacae (8.4%), Pseudomonas aeruginosa (7.2%), and Candida albicans (6.0%). Logistic regression analysis showed that use of straight-catheters was significantly correlated with peritonitis (p= 0.022 OR=2.37 95%CI 1.13, 4.95). Median catheter survival was 50.2 months (range 0.3-120.2 months). Peritonitis was the primary cause of TK catheter removal (46.7%). Kaplan-Meier survival analysis revealed a significantly shorter lifespan of TK catheters in those affected with peritonitis (48.7 months, 95% CI 9.6, 56.4) compared to those without peritonitis (63.7 months, 95% CI 28.0, 99.5). Logistic regression analysis showed that only peritonitis was predictive of poor TK catheter outcomes (p<0.001, OR=4.62, 95%CI 1.13, 4.95). Probability of poor TK outcome=1/(1 + e-r) where r=1.53(peritonitis)-0.71. Conclusion: Peritonitis is an important predictor of poor TK outcome with a shorter lifespan. Introduction: Advanced medico-technological support has enhanced patient survival; other than medical outcome, health-related quality of life (HRQOL) becomes also an important outcome measure for chronic illnesses like those in ESRD program. Method: This study was conducted at our Paediatric Nephrology Centre in June-July 2006 and March-April 2008. In 2006, all Chinese patients aged < 21 years enrolled in ESRD program for more than three months were recruited. In 2008, we recruited new eligible patients, and interviewed again those patients switching from automated peritoneal dialysis (APD) to renal transplantation (TX). A standardized Chinese questionnaire with subsequent transformed scores of 0-100 was used to reflect the HRQOL in 7 aspects, including general well being, physical ability, school/work performance, peer activities and relationships, family activities & relationships, sleep problems, worries and concerns. Result: Twenty-three patients undergoing APD and 27 transplanted patients were interviewed. APD and transplanted patients and their parents gave highest scores to family relationships (83-93) and peer activities & relationships (79-90) and lowest scores to physical activities (44-71). Comparing with APD patients, transplanted patients reported significantly less sleeping problems (92 vs. 80; p=0.019). In parents' perspective, transplanted patients had significantly less sleeping problems (91 vs. 71; p=0.02), better physical activities (67 vs. 44; p=0.045) and higher total scores (80 vs. 68; p=0.042). Six eligible patients switched from APD to TX. After TX, patients and their parents gave higher total and individual scores but all did not reach statistical significance except parents viewed significantly improved peer relationship (89 vs. 80; p=0.011). Conclusion: APD and transplanted patients have not much problems in peer and family relationship despite disease burden. With good dialysis care and support, patients undergoing APD have comparable HRQOL as transplanted patients except significantly more sleeping problems that may be explained by the procedures of APD during sleep.

Sean E Kennedy*, Fiona E Mackie*,**, Gad Kainer*, Elizabeth Craig*, Andrew R Rosenberg*,** *Sydney Children's Hospital, Randwick and **University of N.S.W, Sydney, Australia

We report results of paediatric kidney transplant recipients converted from calcineurin inhibitors (CNI) to sirolimus (SRL).

Since 2003, 15 child/adolescent recipients have received SRL at our centre. All had initially received basiliximab induction with maintenance CNI, prednisone, and either azathioprine or mycophenolate. The median age at time of transplant was 11 years (range 23 m-16 y). SRL was introduced at a median time of 16 months posttransplant (range 2-90 months). CNIs were discontinued in 14 and reduced in 1. All were biopsied prior to conversion. Complete follow up was available for 353 patient-months of SRL treatment (mean 23±13 months/recipient). SRL was discontinued in one because of upper limb oedema and one graft failed due to nonadherence. SRL was otherwise well tolerated. Mean cholesterol levels 12 months after SRL were similar to baseline (4.78±1.25 vs 4.86± 0.77 mmol/L, baseline vs 12 months post conversion respectively) but there was an increase in the use of statin therapy (mean atorvastatin dose 1.7 vs 11.3 mg/day; baseline vs 12 months. P<0.01). No adverse effects of statin therapy occurred. The mean triglyceride level increased with SRL use (2.0±1.7 vs 2.7±1.4; baseline vs 12 months. p<0.05). Haemoglobin levels were stable over 12 months (115±12 vs 117±19; baseline vs 12 months). Four recipients have received darbopoetin therapy. The most recent ten recipients started SRL within 20 months of transplant; all had histological evidence suggestive of either acute or chronic CNI nephrotoxicity. Eight of this group have been followed for at least 12 months. The mean GFR was unchanged during the first 12 months after conversion (64±12 vs 62 ±12 ml/min/1.73m2; baseline vs 12 months after conversion) but had fallen in those seven patients followed for 24 months (55±15 ml/min/ 1.73m2. p<0.05 vs baseline). Four recipients had episodes of steroid reversible acute rejection (AR) while taking SRL. We compared the number of AR episodes in the 9 recipients treated by SRL within 20 months post-transplant to an age-matched historical cohort who had been treated with a CNI based regimen (n=9). All in the control group had been treated for suspected AR between 2 and 5 years after transplant. Rates of rejection after SRL conversion were less than in controls during years 2 to 5 after transplant (0.01 vs 0.1 rejection episodes per month in SRL vs control; p<0.01).

We conclude that SRL conversion is well tolerated by paediatric kidney transplant recipients and offers at least as good a degree of protection form acute rejection as CNI based regimens. Introduction: Chronic PD for children in Singapore was instituted in 1988 at the National University Hospital. However, adult renal nurses provided the dialysis services during the first 10 years. As children with end stage renal disease have special needs, in 1998, a dedicated pediatric renal nursing team was recruited to manage the programme. This study was conducted to determine the impact of the specialist pediatric renal nursing service on PD-related outcomes during the 2 nursing periods. Method: Data from all children (n=82, mean age 12.10±5.33 years) who entered the dialysis program during the two 10-year dialysis periods were analyzed: Period 1 from January 1988 to December 1997 (n=21,) and Period 2 from January 1998 to December 2007 (n=61). Rates of peritonitis, exit site infection, and modality change per patient-year of dialysis were used as indicators of nursing practice. The difference between the 2 study periods was compared using Poisson Regression. Result: The mean ages of the patients at start of dialysis in Period 1 (10.36±5.12 years) and Period 2 (12.70±5.32 years) were similar. The peritonitis rate per patient-year was significantly higher in Period 1 (1.10) compared to Period 2 (0.30), with a relative risk of 1.68 (95% CI 1.13-2.50) (p=0.01). The exit site infection rates per patient-year was also worse in Period 1 (1.21) compared to Period 2 (0.25), with a relative risk of 2.09 (95%CI 1.39-3.13) (p<0.001). Although 38% of children in Period 1 compared to 28% in Period 2 had modality change due to peritonitis, there was no significant difference in the rate of modality change per patient-year between Period 1 (0.21) and Period 2 (0.09). Conclusion: Establishment of a specialist pediatric renal nursing team for the management of children on chronic PD resulted in a significant improvement in the outcomes as measured by the decrease in technique-related complications. Introduction: While most patients with idiopathic nephrotic syndrome (INS) achieve remission with daily corticosteroid therapy, 10-20% are resistant (SRNS) and about 30% show steroid dependence (SDNS). We examined the efficacy of treatment with rituximab, a chimeric monoclonal antibody against CD20 antigen on B lymphocytes, in patients with SRNS or SDNS refractory to standard therapy. Method: Following ethical approval and parental consent, patient demographics, renal diagnosis, previous therapeutic regimens and biochemical parameters such as serum albumin, creatinine, immunoglobulins and urinary protein to creatinine ratio were recorded. Rituximab was administered by IV infusion at a dose of 375 mg / m2 once weekly for 4 weeks in SRNS and for 2 weeks in SDNS. All patients continued to receive therapy with calcineurin inhibitors, alternate-day prednisolone, or both; cotrimoxazole prophylaxis was given for 6 months. For patients with SDNS, rituximab was administered while in remission. Result: Sixteen patients (9 boys) including 11 with SRNS (5 initial resistance; 6 late resistance) and 5 with SDNS, between the ages of 4 and 14 years were included. Renal histology showed minimal change disease (MCD) in 5 and focal segmental glomerulosclerosis (FSGS) in 7 of the patients biopsied. The duration of nephrotic syndrome was 4± 1.2 years prior to inclusion and the mean follow-up after treatment was 1.2±0.4 years. All patients had received conventional immunosuppressive therapy (including cyclophosphamide and calcineurin inhibitors) prior to receiving rituximab. In patients with SRNS, the mean ratio of urinary protein to creatinine decreased from 7.2 at baseline to 1.8 at last follow-up. The mean serum albumin level rose from 1.7 g/dl (1.7 in initial; 1.6 in late resistance) to 2.6 g/dl (1.9 in initial; 3.1 in late resistance) and the mean cholesterol level declined from 482 to 278 mg/dl at last follow-up. The rise in serum albumin was more in MCD group than in those with FSGS, although the difference was not statistically significant. Following treatment, the one-year outcome was as follows: complete remission (1), partial remission (9), non-response (1).In the sub-group with steroid dependence, remission was sustained during a mean follow-up of 0.7±0.1 years. The differences in leukocyte counts and levels of IgG were not significant, serum creatinine levels remained stable throughout the study and none of the patients had serious infections. Conclusion: Rituximab was used in difficult NS with mostly favourable outcome and no serious adverse events. However, the long-term efficacy and safety of rituximab in patients with NS needs further evaluation and prospective randomized controlled trials. Method: This is a retrospective cohort study. Medical records of all patients aged 1 to 18 years with first episode steroid sensitive nephrotic syndrome (SSNS) seen in Princess Margaret Hospital between 1997 to 2006 were reviewed. Patients who were previously treated were excluded from the study. Patients were divided into two groups. Group I included patients treated with short course steroid, while group II included patients treated with long course steroid. Clinical parameters including age, sex, relapse rate, rate of sustained remission, mean duration of hospital stay within the two-year follow up were compared. Result: A total of 46 patients were included in the study. Group I consisted of 22 patients (mean age of 5, M:F=17:5). Group II consisted of 24 patients (mean age of 6, M:F=15:9). The demographics were comparable between the two groups. Patients treated with long course steroid had significantly lower relapse rate (58% versus 90%, P=0.018, fisher's exact test. Odds ratio=7.1, 95%CI 1.35-37.7), higher rate of sustained remission (log rank value=10.5, P=0.0012), and shorter mean duration of hospital stay (16d versus 23 d, P=0.017) at the end of twoyear follow up. No significant side effects of long term steroid such as growth retardation and hypertension were identified. Conclusion: In our experience, 6-month therapy is superior to 2month therapy for the treatment of first episode SSNS in children. It reduces subsequent relapse rate without increasing the frequency of severe side effects related to steroid use. Introduction: Cellular Crescent is a common pathological change of renal disease, which indicates that the renal disease is severe. Since cellular crescent can reverse after timely aggressive therapy, earlier detection of it is of great help for therapy. Although renal pathology is a golden standard for assessment of crescent, its application is limited because of the inherent disadvantage. Glomerular expression of monocyte chemoattractant protein-1 (MCP-1), β-catenin and cytoker-atin19 (CK19) have been confirmed to associate with the severity of cellular crescent, their potential clinical applications were investigated in this study aimed to find non invasive urinary crescent biomarker. Method: Firstly, 124 renal disease patients including 52 with cellular crescent and 72 without cellular crescent, and 20 healthy controls were studied. The urinary level of MCP-1, β-catenin and cytokeratin19 (CK19) were detected by ELISA method. The severity of cellular crescent was reflected by crescent index which evaluated by morphometric method. The sensitivity and specificity of the three molecules in urine for diagnosis of cellular crescent were evaluated by receiver operating characteristic (ROC) analysis. Then, the results were tested by another 80 patients with renal disease including cellular crescent group (n=41) and non cellular crescent group (n=39), and 25 healthy controls. Result: For the first 124 patients, urinary MCP-1, β-catenin and CK19 levels correlated with crescent index significantly (r=0.75, r=0.21, r= 0.63, p<0.01).By ROC analysis, the area under curve (AUC) of urinary MCP-1, β-catenin and CK19 were 0.691, 0.686 and 0.501, respectively. For the second patients group, the AUC of urinary MCP-1, β-catenin and CK19 were 0.83, 0.678 and 0.569, respectively. Conclusion: The urinary level of MCP-1 and β-catenin seemed to be potential non invasive marker for cellular crescent, especially for MCP-1. The finding might help guiding the timely aggressive treatment for patients with cellular crescent. (MsPGN) . The starting dose of CsA was 3-5 mg•kg-1•d-1, adjusted to maintain a trough level of 100~200 ng/ml in the first 6 months. After one year, a low dose of CsA(1~3 mg•kg-1•d-1)with a a trough level of 40~70 ng/ml was accepted to maintain remission for 1 year. Result: (1) Complete remission, partial remission and resistant to CsA were observed in 65%, 20% and 15%, respectively. Eleven patients who was complete remission discontinued CsA, 5 (45%) patients relapsed.

(2) MCNS showed a better response to CsA than non-MCNS, but the difference showed no significant (P>0.05). (3) Hypertrichosis, gingival hyperplasia and hypertension occurred in75%, 25% and 10% of the patients, respectively. Two patients were found to have renal impairment (> 30% rise of serum creatinine) and recovered in 2 weeks. Post-therapy biopsies performed in 3 patients (2 with FSGS and one with MCNS) didn't show relevant tubulointerstitial fibrosis. 2 patients with FSGS of the twenty cases progressed into end-stage renal failure. Conclusion: Long-term CsA treatment was confirmed to be effective in children with SRNS. Renal fibrosis was rare in our patients treated with a low dose of CsA for 2 years.

A Khan, E Aragon, YH Chan, WS Yeo, YW Lau, KH Ng, HK Yap National University Hospital, Singapore

Introduction: Cyclophosphamide remains a significant option in treating children with steroid-dependent and steroid-resistant MCNS despite associated side effects. This study aimed at identifying factors associated with long-term relapsing disease post-cyclophosphamide therapy. Method: Clinical and histopathological data of all children with steroid-dependent or steroid-resistant MCNS who underwent renal biopsy and received 12-weeks of cyclophosphamide as second-line treatment were reviewed. Poor long-term outcome was defined as presence of any immunosuppressive medication 2 years post-cyclophosphamide therapy. Parameters studied included gender, race, age at diagnosis, hypertension, hematuria, and serum creatinine at initial presentation, global sclerosis, mesangial expansion, tubular atrophy and IgM deposits on renal biopsy, and early poor response, defined as no response or relapse within 2 months post-cyclophosphamide therapy. Factors predictive of poor long-term outcome post-cyclophosphamide therapy were analysed by multivariate logistic regression. Result: Forty-six children had MCNS, 21 (45.6%) were steroiddependent and 25 (54.4%) steroid-resistant. Median age at disease onset was 2.9 years (range 1-12.1 years). Mean follow-up period from start of cyclophosphamide therapy was 11.53±6.35 years. Twenty-nine (63%) children responded to cyclophosphamide initially, however 2 (6.9%) relapsed within 2 months post-cyclophosphamide therapy. Seven (15.2%) were hypertensive, 7 (15.2%) had hematuria and 4 (8.7%) had elevated creatinine at presentation. Thirty-one (67.4%) of biopsies were positive for mesangial IgM, 10 (21.7%) had global sclerotic lesions and 11 (23.9%) had tubular atrophy. Regression analysis showed that only early poor response to cyclophosphamide was predictive of poor long-term outcome (p<0.018, OR=5. 8, ). Using this model, the probability of poor long-term outcome post-cyclophosphamide therapy was expressed by the equation: P=1/(1+exp-r), where r=1.75(early poor response)-0.74. Early poor response to cyclophosphamide had a positive predictive value of 84.7% in predicting poor long-term outcome. Conclusion: Steroid-dependent or resistant MCNS patients with early poor response to cyclophosphamide therapy were more likely to have long-term relapsing disease requiring immunosuppressive therapy. Introduction: Glucocorticoids are mainstay of management of nephrotic syndrome. Deflazacort is a newer glucocorticoid which not only have similar efficacy but also lower incidence of side effects compared to prednisolone, however its high cost is the major drawback. In order to assess whether Deflazacort can replace prednisolone we compared effectiveness and the adverse effects of prednisolone and Deflazacort. Method: 60 patients (30 on deflazacort therapy & 30 on prednisolone therapy) of Nephrotic syndrome in Nephrology Unit, Pt.J.N.M.Medical College & GBG Kidney care Hospital, Raipur from april2007 to april2008 were studied. All patients were subjected to routine investigations. Result: •Among the patients treated with prednisolone 66.67% were having hypocalcemia whereas it was 40% among the patients treated with Deflazacort (p value<0.001). •Hyperphosphatemia was present in 40% of the patients on prednisolone while it was 20% among the patients on deflazacort (p value<0.005). •40% of the nephrotic syndrome patients treated with prednisolone had raised calcium phosphate product while it was raised in 20% of the patients treated with Deflazacort (p value<0.005). •70% of the patients on prednisolone therapy had hypercholesterolemia whereas it was 53.33% with Deflazacort therapy (p value<0.02). •Posterior subcapsular cataract developed in 6.66% of the patients treated with prednisolone while none of the patients with deflazacort developed it. •80% of the nephrotic syndrome patients treated with prednisolone had steroid induced side effects like cushing's habitus (moon like face), purple striae, muscular weakness, psychiatric disturbances while it was seen only in 40% of the nephrotic syndrome patients treated with Deflazacort (p value<0.001). •Relapse rate was 30% among the patients treated with Deflazacort while it was 43.33% with prednisolone (p value<0.1).

Conclusion: This study demonstrate that although deflazacort is mild expensive than prednisolone it was as effective as prednisolone and further more it had fewer steroid induced side effects. Introduction: Urinary tract infections(UTIs) are not uncommon findings in febrile pediatric patients and approximately one third of patients of UTI may have renal scars. This research was intended to establish the relationship between duration of fever and renal scars. Method: 143 patients medical records were reviewed retrospectively. Inclusion criteria were as follows: 1) fever as defined by an axillary temperature ≥37.5°C, 2) accurate history of fever duration and the use of antibiotics 3) no previous history of UTI and 4) positive urine culture. We observed whether the longer fever duration could be associated with the development of initial renal defects and subsequent renal scars, increased C-reactive protein(CRP), leukocytosis and the presence of vesicoureteral reflux(VUR). Result: 1) Patients with longer fever duration after antibiotics showed more frequent initial renal defects(P=0.014). However, fever duration before antibiotics was not associated with the development of initial renal defects(P=0.244). 2) Incidence of renal scar was increased with fever duration before antibiotics(P=0.006) and fever duration after antibiotics(P=0.015). 3) CRP was correlated with the fever duration after antibiotics(r=0.287, P=0.003). 4) There were no relationships between fever duration and VUR(P>0.05). Conclusion: Our data suggest that fever duration before/after antibiotics are significantly associated with the increased development of renal scars in pediatric UTI. Introduction: Universal agreement in investigating urinary tract infection (UTI) in children with imaging is lacking. This study serves to evaluate the selective approach of imaging infants < 6 months old with UTI according to risk features suggested in UTI Guidelines by National Institute for Health and Clinical Excellence (NICE) 2007. Method: This is a retrospective study of infants < 6 months old with first UTI from Jan 02 to Dec 06 having complete set of imaging studies including ultrasound kidneys (US), micturating cystourethrogram (MCU) and DMSA scan at > 6 months (those with known urological abnormalities and antenatal hydronephrosis were excluded). They were evaluated against a set of risk features according to NICE UTI guidelines i.e. serious illness, poor urine flow, abdominal mass, raised SCr, septicaemia, non-Ecoli UTI and failure to respond to treatment with suitable antibiotics within 48 hrs. Those having any one of these were classified as atypical and those having none as typical.

Result: 165 cases were identified. 115 infants having all three imaging studies completed were reviewed. Atypical group (32) had risk features of non-Ecoli UTI in 16, septicaemia 7 and failure to respond to antibiotics 9. None had other risk features. There were 6 scars, 26 refluxing ureters and 6 hydronephrosis (> 5 mm). In typical group (83), there were 23 scars, 22 refluxing ureters, 5 hydronephrosis, 2 hydroureter-hydronephrosis and 1 PUJ. 76 infants had normal US; and if only those (7) with abnormal US were further investigated as suggested by the Guidelines, 18 refluxing ureters and 23 scars would be left undiagnosed. Conclusion: According to the NICE UTI Guidelines, typical UTI will only be investigated with US, and only abnormal US will be followed by MCU. For the present group, the suggested selective imaging approach would leave a significant number of VUR and renal scars undiagnosed. Not until the significance of long term outcome of scars & VUR is clarified definitely, it may not be an optimal practice for infants < 6 months old with first UTI. Introduction: Introduction: Percutaneous renal biopsy is a safe procedure. Fear of complications require hospitalization adding to treatment cost, which may be avoided. Aim: To study the timing of complications associated with a percutaneous kidney biopsy in children in order to determine the feasibility of it being performed as a day-care procedure. Method: Material and Methods: Children undergoing kidney biopsy over 2 yrs included prospectively. Coagulation studies and renal parameters noted. Procedure not carried out under real time ultrasonography. Children sedated with midazolam and ketamine. Vital parameters monitored as a baseline and complications noted on a 3 hrly basis for 24 hours post-procedure, for timing of onset and duration. Statistical analysis: Univariate analysis using chi-square test. Result: Results: 90 children (M:F::2:1) age11 m-12 y underwent a kidney biopsy. Nephrotic syndrome with atypical features was the commonest indication. Hematuria noted in 27% but only 3.3% required a transfusion. No child required any surgical or radiological intervention. All complications when occurred had onset < 6 hrs but most resolved by 12 hrs. Only 6 (6.6%) children continued to have hematuria beyond 12 hrs and this continued beyond 24 hrs. The occurance of a complication had no bearing to the age, gauge of needle used, baseline serum creatinine or the underlying kidney disease. Monitoring of vital parameters could not predict hematuria before it was manifest. Conclusion: Conclusions: Age, underlying renal disease, baseline investigations and monitoring of vital parameters could not predict significant hematuria early. Complications after a kidney biopsy are obvious by 6 hrs, resolving in most within 12 hrs. All patients undergoing kidney biopsies should be kept under observation for minimum 12 hours. Those with macroscopic hematuria beyond 12 hrs or requiring intervention may be admitted. In others the kidney biopsy can safely be carried out as a daycare procedure. Introduction: Between 2003 and 2008 urine screening was carried out in some kindergartens and schools in Shanghai. We hope to discuss the characteristics of kidney diseases detected in urine screening. Method: In Shanghai 46,171 school children (2003) (2004) (2005) and all children in kindergartens (2006-2007, about 270 ,000 children/year) underwent urine screening. Children with abnormal results were asked to be followed up in designated hospitals. We documented and analyzed the follow-up records. Result: During 2003-Feb 2008, 419 children (207 boys and 212 girls, from 2-year to 18-year) with abnormal screening results went to the hospitals, among whom 367 were hematuria, 36 were proteinuria, 5 were hematuria combining with proteinuria, 11 were leucocyturia and 4 cases diagnosed as nephrotic syndrome. 39 cases underwent renal biopsies which consisted of 32/39 hematuria, 3/39 proteinuria, 3/39 nephrotic syndrome and 1/39 hematuria with proteinuria. The pathologic diagnosis showed as following: 20/39 showed minor change, 2/39 minimal change disease (MCD), 7/39 IgA nephrology (IgAN), 7/39 thin basement membrane nephrology (TBMN), 2/39 mesangial proliferative glomerulonephritis (MsPGN), 1/39 focal segmental glomerulosclerosis (FSGS). We noticed that four patients with nephrotic syndrome were detected in kindergarten by urine screening. Seven children were diagnosed with IgAN by renal biopsy. 4/7 were long term hematuria, 2/7 proteinuria and 1/7 hematuria associating with proteinuria. Conclusion: Most problem detected in urine screening was mild in our study but some may have poor outcome which needed close follow-up for a long time. Urine screening was well done in kindergartens in Shanghai. Introduction: The prevalence of obesity all over the world has been rising. It is well documented that obese patients are at greater risks to develop hypertension, coronary vascular disease, and insulin resistance, and more attention has been paid to the impact of obesity on kidney, recently. Since the first description regarding the relationship between massive obesity and proteinuria in 1974, increased evidence demonstrated that obesity-related glomerulopathy (ORG) should be identified as an isolated complication of obesity in adults. It is, however, unclear whether this condition exists even in children with obesity. This study was conducted to know whether obese children have higher risk of developing to ORG as well as in adult.

Method: Eighteen hundred and thirty nine children aged 6-14 years with abnormal urinary findings by the screening program in Tokyo in 2007 were enrolled. Tentative diagnoses were made based on the criteria for this program (Kaneko K, et al. Pediatr Nephrol 19:499; An obesity index based on the standard weight was compared among the groups using Kruskal-Wallis test. P value less than 0.05 was considered significant. Result: The obesity index (%) was significantly higher in group F (nephritis/ suspected nephritis) than in other groups: (mean ± standard deviation:group A 2.1±15.4, group B -3.6±12.6, group C -3.3±18.1, group D 2.7±15.3, group E 3.9±15.0, group F 8.8±23.1, P<0.05). The number of obese children defined as an obesity index of 20% or more was greater in group F (18.5%) than in group A (10.0%). Conclusion: ORG develops even in childhood and early intervention to lose weight should be considered, as the benefit of weight loss in ORG in adult is reported to be limited.

Sethi SK, Dragon-Durey M-A*, Dinda A**, Hari P, Bagga A Departments of Pediatrics and Pathology**, All India Institute of Medical Sciences, India Service d'Immunologie Biologique, Hôpital Européen Georges Pompidou, France* Introduction: Mutations in genes encoding complement regulators predispose to development of atypical HUS. We examined for abnormalities of the complement pathway in patients with atypical HUS. Method: EDTA samples were collected from index patients presenting with atypical HUS and their families, before instituting plasma therapy or blood transfusion. Plasma concentrations of C4, C3, factors B, H and I, CD46 and anti-factor H antibodies were measured. Genes encoding factor H, I and CD46 were sequenced. Screening by multiplex ligation-dependent probe amplification for complement factor Hrelated (CFHR) 1 and CFHR3 genes was performed. Patients with anti-factor H antibodies received double-volume plasmapheresis daily till activity subsided, followed by 4 alternate-day and 4 twice-weekly plasmapheresis. They also received IV immunoglobulin (2 g/kg), IV cyclophosphamide (500 mg/m2 q 3-weekly) and prednisolone (1 mg/kg). Result: Fourteen patients (12 boys) from 7 months to 15 yrs were studied. Renal histology showed features of thrombotic microangiopathy involving arterioles and capillaries. One patient had complete deficiency of factor H due to a homozygous mutation. Eight patients tested positive for anti-factor H antibodies (titer 194-32,000 UA); 7 had antibody titer above 1500 UA and were dialysis dependent. The antibody titer and disease activity reduced in all patients; 7 progressed to end stage renal disease. Genetic studies showed homozygous deletion of CFHR1 and CFHR3 genes in 4 patients with anti-factor H antibodies. Conclusion: Antibodies to factor H appears to be an important cause of atypical HUS in India. The antibody titer correlated directly with the disease severity. Deletion of CFHR1 and CFHR3 genes might genetically predispose to development of anti-factor H antibodies, and occurrence of HUS. Introduction: To determine the safety and effectiveness of oral highdose mizoribine (MZR) for children with severe Type 1 membranoproliferative glomerulonephritis (MPGN). Method: Between 2003 and 2007, 5 children diagnosed with primary Type 1 MPGN by renal biopsy were treated with intravenous highdose methylprednisolone pulse therapy, followed by alternative-day prednisolone that was slowly tapered off over several years. However, 2 of them continued to show signs of proteinuria and hypocomplementemia or disease flare despite steroid therapy, and they were both were diagnosed with severe Type 1 MPGN. Each patient underwent a repeat renal biopsy at 23 or 19 months after the first biopsy. Repeat biopsy findings revealed no histological improvement in either of them. Therefore, they were both administered with daily oral MZR due to unsatisfactory steroid effects. The dose of MZR was adjusted to achieve a peak blood level of around 3.0 mcg/ml to maximize clinical efficiency. Result: Urinary protein excretion decreased from 3+ to trace in one of the patients at 18 months and from 2 + to negative in the other at 13 months after starting MZR therapy. The serum C3 level increased to the normal level in the patient with persistent hypocomplementemia. The dose of prednisolone was also tapered in both. Neither of them developed adverse reactions. Conclusion: Our results suggested that MZR at an optimal blood concentration is effective and safe for patients with severe Type 1 MPGN. Further evaluation is warranted for the use of MZR therapy in a long-term follow up study, and children with severe type 1 MPGN should be included in a prospective-randomized trial of MZR therapy.

Hari P, Bagga A, Gupta N, Hari S, Mahajan P, Yadav A Departments of Pediatrics and Endocrinology* All India Institute of Medical Sciences, Ansari Nagar, India Introduction: Vitamin D insufficiency (serum 25-hydroxyvitamin D (25,OHD) level < 30 ng/ml) is common in patients with CKD and may contribute to mineral bone disease. We estimated the prevalence of vitamin D insufficiency in children with CKD, and examined the effect of cholecalciferol supplementation on serum levels of 25,OHD, intact parathyroid hormone (PTH), calcium and phosphorus. Method: In a prospective interventional study children with estimated GFR between 15 to 89 ml/min/1.73 m2 were given 6, 00,000 IU of cholecalciferol. Children on vitamin D supplements and those with serum calcium level >10.5 mg/dl and phosphorus > 6.0 were excluded. Primary (25,OHD, PTH levels) and secondary (calcium, phosphorus, alkaline phosphatase levels and urinary protein excretion) outcomes were measured at baseline and 6 weeks. Result: 40 children (85% boys) with a mean age of 7.7±3.8 (range 2-15) yr were studied. 33 (82.5%) children had vitamin D insufficiency at baseline. Of these, 15 children had 25,OHD levels < 15 ng/ml. The median serum 25,OHD levels increased from 18.6 (95% confidence interval [CI], ng/ml at baseline to 48. 5 (42.1-56.8) ng/ ml at 6 weeks (P=0.000) while the PTH levels declined from 55.3 (47.1-77.8) pg/ml to 41.4 (31.2-56.8) pg/ml (P= 0.01). The calcium, phosphorus and alkaline phosphatase levels did not change significantly from the baseline. The median urinary protein to creatinine ratio decreased from 0.30 (0.03-1.5) to 0.61 (0.08-2.26) mg/mg (P=0.07). There was no correlation between serum 25,OHD and PTH levels. Conclusion: Vitamin D insufficiency is highly prevalent in children with CKD and cholecalciferol supplementation appears to be an effective treatment in correcting vitamin D status and reducing PTH levels. Introduction: The aim of this study was to explore the role of human adipocyte derived stem cells (hADSCs) in a repair of acute renal failure. Method: For renal failure, acute ischemic tubular necrosis was induced Spraque-Dawley rats by clamping bilateral renal arteries for 40 min. hADSCs obtained from elective liposuction procedures. After steps of isolation, stem cells were seeded at 1~2×105/cm2 in complete medium. Dextran-coated iron was used as a labeling agent and Poly-llysine (MW 70~150 kDa) as a transfection agent. Before releasing the clamps, three shots of iron labeled stem cells (1×106/0.2 cc) for left kidney or PBS for right kidney were injected at upper, middle and lower part of renal cortex directly. MRI images, one day after reflow, confirmed presence of iron labeled cells in the renal cortex. The examination on both kidneys was done after 1, 3 days, 1,2,4,6,10 and 15 weeks(n=5 in each). The evaluation of the degree of tubular necrosis (PAS stain) and the locations of stem cells(prussian blue stain) was done by light and electron microscopically. Result: Serum creatinine on day 1 was 2.7±0.4 mg/dL, on day 3, 2.2 ±1.4 mg/dL and on the first week 0.8±0.3 mg/dL. After then, it has no significant change among groups. Tubular injury was scored by counting the number of damaged tubules in random selected 100 cross sectioned tubules. On day 1, 47±16 of left side and 76±11 of right; day 3, 11±17 and 55±21 were scored. From 1 week group, the tubular necrosis had been recovered well. Cells positive stained for prussian blue located at peritubular area. However, tubular epithelial cells or glomerular cells were not positive. Electron microscopically, fine iron granules with electron density were found in their cytoplasm, which were thought as injected stem cells. FISH for anti-human chromosome (CEP) 17 probe were positive to those cells. Conclusion: We demonstrate stem cells contribute to repair the tubular epithelium in acute renal failure model, not by tubulogenesis directly but by indirect effects, which should be evaluated. Introduction: A composite heterozygous NPHS2 mutation was verified for the first time in a Chinese familial FSGS, which resulted in a truncated (podocinV165X) and a missense mutant podocin (podocinR168H). Both mutant sites were localized to a same domain in podocin C-terminu. Nevertheless, our previous studies showed that the binding characteristics of both mutant podocins with N-and C-terminal antibodies were obviously different, which suggested that the two mutant podocins might play a different role and involve different pathogenesis. This study here aimed to explore the different roles of the two mutant podocins on podocyte injury via in vitro experiment. Method: Immortalized mouse podocyte was transfected with the vectors containing wild or mutant podocins. Podocyte injuries were evaluated by FITC-Annexin V. Effects of wild and both mutations on nephrin, CD2AP and the recently identified podocyte ion channel TRPC6 were displayed by immunofluorescence staining and western blot. Cytosolic free Ca2+ was measured with fluo-3AM. To evaluate TRPC6 role in cell injuries, podocyte was co-transfected with TRPC6 siRNA and wild or mutant vectors. Result: Both wild and mutant podocins significantly increased podocyte apoptosis. Wild and V165X was partially targeted to membrane, whereas R168H was only distributed around nuclei. Both wild and mutant podocins showed co-localization with nephrin, CD2AP and TRPC6. Nephrin, CD2AP and TRPC6 were obviously up-regulated in R168H-podocytes, while TRPC6 and CD2AP was evidently increased in wild and V165X-podocytes, respectively. A cortical cytoskeleton was observed in wild and V165X-podocytes, whereas R168H seriously disturbed cytoskeleton arrangement. Both wild and mutant podocins increased cytosolic free Ca2+ level. Podocyte apoptosis, Ca2+ level and expressions of other slit diaphragm molecules did not change in just TRPC6 knockdown cells. With the knockdown of TRPC6, Ca2+ level and podocyte apoptosis decreased significantly only in wild and V165X-podocytes. Conclusion: PodocinR168H caused much more significant changes of podocyte molecules and cytoskeleton, which prompted that podocinR168H plays more critical role on podocyte injury. Method: Forty-one children aged 1 year to 18 years admitted at St AlZahra Hospital, Isfahan and St Ali Asghar Hospital, Tehran, Iran with biopsy proven idiopathic FSGS were enrolled. They were divided into two groups according to the time of progression to renal death. Renal death was defined as glomerular filtration rate (GFR) less than 50 ml/min/1.73m 2 or decreasing GFR more than two times compare to the baseline. Reaching renal death in less or more than two years was assumed as rapid progressors (RP) or slow progressors (SP) respectively. The intron 16 of ACE gene was amplified by PCR technique.Statistical significance was regarded as P<0.05. Result: Twenty-eight patients were male and 13 were female.In 15 RP patients the genotype distribution was DD-26.6%,II-6.7%,ID-66.7%.In 26 SP patients the genotype was similar (DD-38.6%,II-7.6%,ID-53.8%, P>0.05). There were no statistically significant differences for ACE I/D gene polymorphism between two groups of patients (p>0.05). Conclusion: Our study revealed no correlation between ACE I/D gene polymorphism and rapidity of progression of FSGS to ESRD in Iranian children. Introduction: Some studies have shown that molecules produced by podocyte may influence glomerular endothelial barrier properties. we found the level of Angiopoietin-like protein 3 (Angptl3) mRNA was significantly increased in kidneys of children with minimal change nephrotic syndrome and the level of Angptl3 was increased in the glomerulus of adriamycin rats along with the development of proteinuria. We also confirmed expression of Angptl3 in cytoplasm of podocyte. Experiments confirmed that Angptl3 could bind to integrin αvβ3 of umbilical venous endothelial cell. Integrin αVβ3 is also one of the integrin heterodimers that the glomerular endothelial cells (GEnCs) express. So, we postulate Angptl3 secreted by podocyte have effect on GEnCs and may take part in development of proteinuria. The aim of this study was to investigate the effect of Angptl3 on the barrier properties of GEnCs and the possible signaling pathway. Method: Permeability of GEnCs was assessed by transendothelial resistance (TEER) and by the diffusion of fluorescein isothiacyanatelabeled bovine serum albumin (FITC-BSA). The level of phosphospecific Akt were delected by Western blot. Result: We demonstrated that Angptl3 induced decrease in TEER and increase in permeability rates for FITC-BSA, and phosphorylation of Akt was markedly evaluated after GEnCs was treated with Angptl3. We showed pretreatment of LY294002, a PI3K inhibitor, prevented Angptl3-induced decrease in TEER and inhibited increase in FITC-BSA.

We observed pretreatment of LM609, a specific integrin αVβ3 antibody, could significantly blocked Angptl3-induced Akt phosphorylation increase, and inhibited decrease in TEER and increase in FITC-BSA. Conclusion: Theses studies indicate Angptl3 could significantly increase the permeability of GEnCs monolayer via integrin αVβ3 and PI3K/Akt signaling pathway. Introduction: Intrauterine growth restriction (IUGR) is associated with hypertension, diabetes and chronic kidney disease in adulthood. Postnatal overnutrition following IUGR may be of pathogenic importance for the development of diabetes and cardiovascular disease. Our previous animal studies have shown IUGR adults have higher urinary excretion of protein and blood pressure than controls and postnatal overnutrition following IUGR cause more severe hypertension and proteinuria than IUGR itself. The aim of this study was to identify the possible pathogenesis of kidney disease in IUGR and the effect of postnatal overnutrition by comparative proteomic approach. Method: IUGR was induced in rats by isocaloric protein restriction in pregnant dams. IUGR pups were divided into two groups, fed either standard-protein diet (IUGR group) or high-protein diet (HP group). At the age of 12 weeks, kidney proteins were obtained from each group. 2-DE, staining, mass spectrometry and database searching were used. The 2-DE test was repeated three times in each group. Result: The 2-DE image analysis detected average 727 +/-58 spots in IUGR group, 740 +/-43 spots in HP group and 758 +/-53 spots in control group. The differential proteomic expression analysis between IUGR and control group found 12 proteins had significantly differential expression, which were transcription regulators including prohibitin and ribonuclease UK114, structural molecules including capping protein, enzymes including glutathione s-transferase alpha-1, retinal dehydrogenase1, transketolase and so on. Subsequently, the differential proteomic expression analysis between IUGR and HP group found 16 proteins had significantly differential expression, which were transcription regulators including ribonuclease UK114 and NADH-ubiquinone oxidoreductase, structural molecules including ezrin and gamma-actin, enzymes including catalase, isocitrate dehydrogenase and so on. Conclusion: Data from this study may provide, at least partly, valuable experimental evidence of proteins involved in the pathogenesis of kidney disease in IUGR and the effect of postnatal overnutrition. Introduction: NPHS2 exonic mutations have been reported extensively in sporadic primary nephrotic syndrome (NS) in Caucasian populations, but are uncommon in Asians. This study examined the NPHS2 promoter region for gene variants and analysed their association with NS in Singapore Chinese children. Method: Direct sequencing of the 5' promoter and all 8 exons of NPHS2 was performed on genomic DNA from 58 patients with primary sporadic NS (age of diagnosis ranging from 1-20 years) and 55 normal controls. Statistical correlation of genotype with disease was performed using SNPStats (http://bioinfo.iconcologia.net/index. php?module=Snpstats). Result: We identified five NPHS2 single nucleotide polymorphisms (SNPs) in our patients and controls -three were located in the 5' promoter region (-670C/T, -116C/T and -51G/T); with two in exon 8 (954T/C and 1038A/G). No missense mutations were found. The genotype frequencies were consistent with Hardy-Weinberg expectations. The SNPs in the promoter region were found to be associated with NS under different model fits (-670C/T, recessive model, p= 0.042; -116C/T, over-dominant model, p=0.019; -51G/T, additive model, p=0.039). No association with NS was observed for the SNPs in exon 8. Haplotype analysis was performed subsequently for the three promoter region SNPs, which were only weakly linked (-670C/T and -116C/T: r2=0.346, p=0; -670C/T and -51G/T: r2=0.215, p=0; -116C/T and -51G/T: r2=0.098, p=7e-4). Four haplotypes: TCG, CTG, CCT and CCG were observed. The haplotype CCT, was significantly associated with NS (OR: 2.4, 95%CI 1.05-5.50) (p= 0.04). This haplotype was responsible for 20% of nephrotic patients, but was only present in 9% of healthy controls. Thirty of the 58 patients (51.7%) were steroid-resistant. Further analysis revealed that the haplotype frequency was 25% in steroid-resistant patients, twofold that of steroid-dependent patients (14%). Conclusion: The promoter haplotype of NPHS2 may confer susceptibility to sporadic NS. Functional studies are needed to validate this hypothesis and elucidate possible disease-causing mechanisms. Introduction: The actin cytoskeleton is thought to play a critical role in maintaining podocyte structure and function. Some evidences have shown that angiotensin II (AngII) could induce the cytoskeleton changes in podocytes. Nevertheless, the relevant signal transduction pathway is not fully clarified. Some studies suggested that ERK1/2 MAPK pathway might be connected with the cytoskeleton of some types of cell. Here, it was explored whether ERK1/2 pathway is involved in the effects of AngII on podocyte actin cytoskeleton. Method: Mouse podocyte clone (kindly provided by Prof. Peter Mundel) was cultured at 33°C for proliferation,then transferred to 37°C and cultured for 1 week to be differentiated. After podocyte was treated with AngII (10-7M) for 2, 5, 10, 15, 30, 45 and 60 min, the protein expressions of ERK1/2 and phosphorylated ERK1/2 were detected by western blotting. TRITC-phalloidin was directly used to stain the actin filaments (F-actin) of podocytes. To verify the key role of ERK1/2 in the podocyte cytoskeleton alterations resulted from AngII, U0126, the specific inhibitor of ERK1/2 pathway was applied for 1 h before AngII treatment.

Result: Phosphorylated ERK1/2 increased markedly (P<0.05) at 15 min and persistently to 60 min after AngII treatment. Normal podocytes displayed an obvious and parallel actin stress. In AngII treated podocytes, a cortical pattern of F-actin mainly on cell membrane was observed at 30 min, and marked depolymerization of which occurred obviously at 45 min and persisted to 120 min. Pretreated with U0126 for 1 h, the ERK phosphorylation was completely inhibited, and the abnormal arrangement of F-actin was partially attenuated in AngII treated podocytes. Conclusion: AngII activated the ERK1/2 MAPK pathway, which at least partially contributed to the rearrangement of podocyte actin cytoskeleton induced by AngII. Introduction: Nephrotic syndrome is one of the most common problems among the renal diseases in children. Many patients, about 40% of whom responded well previously to prednisolon, however, relapse frequently, when treatment with prednisolon is tapered off or stopped. Factors for predicting such relapse are yet to be established. Dyslipidaemia during remission could be a predictor of relapse in nephrotic syndrome Method: A total of 26 hospitalized children of 1-8 years age, suffering from nephrotic syndrome 1st attack were included as cases. Another 22 hospitalized children of same age group, not suffering from any kind of renal diseases, were included as controls. Lipid profile were measured in both cases and controls after initial enrollment. All the cases were treated with oral prednisolon adequately according to ISKDC protocol. During remission, lipid profile were again measured and on the basis of presence of abnormal lipid profile at that time, cases were divided into 2 groups. All the cases were followed-up every monthly for subsequent 6 months to observe development of subsequent relapse. Result: Among the cases, group-I consisted 16 patients who had normal lipid profile during remission and group-II consisted 10 patients who had abnormal lipid profile during remission. Both groups of cases showed higher mean level of s.cholesterol(p<0.001), s.LDL (p<0.001), s.TG (p<0.001) and s.Lp(a) (p<0.001) than those of controls during initial diagnosis. During remission, group-II patients showed higher mean serum cholesterol (332.9±105.19 mg/dL vs. 183.13±16.89 mg/dL; p<0.001), serum LDL (252±101.67 mg/dL vs. 119.19±21.33 mg/dL; p<0.001), and serum TG (182.8±73.83 mg/dL vs. 93.31±20.95 mg/dL; p<0.001). 5 patients out of 10 patients of group II (19% of total case) developed subsequent relapse within 6 months follow-up. Among the relapsers, mean cholesterol (334±46 vs. 232±34 mg/dL; p<0.05) was significantly higher than that of nonrelapsers of group-II patients. On the other hand, no patient of group-I developed relapse within 6 months follow-up. Conclusion: It may be concluded from the present study that elevated lipid profile, specially serum cholesterol during initial remission, may be a predictor of subsequent relapse in idiopathic childhood nephrotic syndrome. Result: Abnormal urine analysis were found in 20.95%(total 22) of sibling contacts. The incidence of nephritis among 105 siblings was 12.38%(13 siblings). This was clinical in 5(4.76%) and subclinical in 9(8.57%) cases and the calculated ratio of subclinical 

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AI-044: CLINICO-PATHOLOGICAL ANALYSIS OF 24 BOYS WITH LUPUS NEPHRITIS

Method: Retrospective study was taken by analyzing the data of clinical, renal pathology and follow-up survey of 24 boys with LN. Result: All boys suffered from LN at the average age of 11.2±1.9 years old. The course of disease before diagnosis was 9.3±24.8 months(range from 1 to120 months). 4 cases of them were misdiagnosised for a long time as HSPN, NS or AGN. Among our boys, kidney damage was the first manifestation in ten cases(41.7%), and 2 cases(8.3%) only had LN. 23 cases(95.8%) were accompanied with proteinuria(24 h-Upro eduction ranged from 0.87 g to 16.98 g). 5 of 23 cases(20.8%) had decling renal function. Nephrotic syndrome was the main clinical types (45.8%). Renal biopsies were performed in 19 cases. Class IVLN (57. 9%) was the most frequent pathological findings, and "full house" was found in 68.4% of biopsies. All patients were taken by the treatment of steroid and immunosuppressive agents. Sixteen boys obtained clinical remission after average 3.4 months, and the remission rate was 66.7%. Six cases (25%) relapsed during follow-up survey, and two cases suffered from renal failure. Conclusion: In boy's LN, nephrotic syndrome was the main clinical manifestation, and class IVwas the main pathology type. Lower morbidity and atypical clinical symptom were main reasons of misdiagnosis and missed diagnosis

AI-062: INTRAVENOUS DEXAMETHASONE FOLLOWED BY ORAL PREDNISOLONE VERSUS ORAL PREDNISOLONE IN THE TREATMENT OF CHILDHOOD HENOCH-SCHÖNLEIN PURPURA

Severance Children's Hospital

This study examined the outcomes of children with proliferative lupus nephritis using a new mycophenolate (MMF)-based protocol comprising pulse intravenous methylprednisolone, MMF +/-cyclosporine for induction. Method: Sixteen children with proliferative LN, WHO class III and IV (age range at start of treatment 3.7-14.8 years) who were treated between the years 1995 to 2007 were included in this retrospective study. MMF dose was 1200 mg/m2/day. We compared the clinical and laboratory parameters pre-induction, at 6 months and at 1 year. Treatment outcome was defined by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), renal function, proteinuria and serologic markers (complement C3, C4 and anti-dsDNA)

THE ROLE OF VASCULAR ADHENSION MOLECULE-1 AND INTERCELLULAR ADHENSION MOLECULE-1 IN CHILDREN WITH SLE

We sought to investigate ICAM-1 and VCAM-1in peripheral blood and the expression of ICAM-1and PHB in renal tissues of SLE children, and to explore the relationships between adhension molecules and active state of SLE. Method: Soluble ICAM-1 (s-ICAM-1) and soluble VCAM-1(s-VCAM-1) were detected by using ELISA. CD54 (ICAM-1) and CD106 (VCAM-1) on peripheral blood mononuclear cells were detected by using flow cytometry. Expression of ICAM-1 and PHB in renal tissues were detected by using immunohistochemistry respectively

Conclusion: s-ICAM-1 might be a predictor to reflect the active states of SLE children. ICAM-1 and PHB may be another early monitoring factors in renal injury of SLE children

According to different outcomes, patients were divided into remission group (complete remission and partial remission) and ineffective group (nonresponse and death); according to different recipes in induction treatment, divided into cyclophosphamide (CTX) group, mycophenolate mofetil (MMF) group and other drugs group; according to whether receive renal biopsy and pathological classification, divided into type I and II group, type III and IV group, type V group and no biopsy group. Data was analyzed by univariate χ2 test and multivariate logistic regression model using SPSS 11.0. Result: Univariate analysis showed that the following 4 variables were correlated to prognosis: different pathological types (P=0.005), heavy proteinuria at onset(P=0.003), different recipes (P=0.001) and irregular treat (P=0.000). In multivariate analysis, it was confirmed that irregular treatment (OR=9.955) was significantly associated with treated outcome. Conclusion: For all SLE patients with evidence of nephritis, we should do our possible to perform renal biopsy

STUDY OF RENAL ABNORMALITIES IN RELATION TO CD4 LEVEL IN HIV POSITIVE PATIENTS OF PEDIATRIC AGE GROUP FROM TRIBAL

Result: •Males were 60% & females were 40%. •Low CD4 percent (<25) was found in 75% of patients. •In patients with CD4 percent <25, Males were 53.33% while females were 46.67%. •90% of patients had proteinuria(>200 mg/24hours). •Among the patients with CD4 percent <25, 93.33% had proteinuria (>200 mg/24hours) while it was present in 60% of patients with CD4 percent>25. •95% patients had Hemoglobin(Hb) level <11 gm%. •Hb was <11 gm% in all the patients with CD4 percent <25. •In the patients with low CD4 percent (<25) with proteinuria, 35.71% had malnutrition (Mid arm circum-ference<13.5 cm) & among the patients with CD4 percent >25, 20% had malnutrition. •Among the patients with duration of illness >6months, 88.88% had low CD4 percent(<25) with renal insufficiency, while it was present in 63.63% of patients with duration of illness <6 months. •Tuberculosis infection was present in 15% of patients with low CD4 percent(<25) with renal injury. Conclusion: •HIV infection with proteinuria was more common in male children. •Low CD4 percent(<25) with renal injury was more common in males as compared to females

•Low CD4 percent with proteinuria had significant Hyperlipidemia. •Malnutrition was more common in patients with low CD4 percent & proteinuria. •Duration of illness had negative relationship with CD4 percent with renal insufficiency. •Tuberculosis infection was much more common in low CD4 percent with renal injury

AJ-006: SEVEN YEAR FOLLOW UP OF MICROSCOPIC POLYANGIITIS PROGRESSED TO CHRONIC SCLEROSING GLOMERULONEPHRITIS: A CASE REPORT

Result: The diagnosis of patient's first renal biopsy was MPA, P-ANCA associated crescentric glomerulonephritis. The patient's second renal biopsy was done 5 years 6 months later since first renal biopsy, and pathologic diagnosis was chronic sclerosing glomerulonephritis, advanced, due to MPA. We began methylprednisolone pulse therapy, combined with a low dose of cyclophosphamide and plasmapheresis therapy in 2001, and ACE inhibitor, Angiotensin II receptor blocker, cyclophosphamide were used until now and the patient's current age is 14 years old. The patient's laboratory findings showed BUN 117 mg/ dL/Cr 2.3 mg/dL at initiation of disease, BUN 30.5 mg/dL/Cr 1.6 mg/ dL in 2004, BUN 30.7 mg/dL/Cr 1.6 mg/dL in 2006. But renal function was progressed to chronic failure with latest laboratory data BUN 51.7 mg/dL and Cr 3.2 mg/dL. Conclusion: We report a case of long-term follow-up and survival for 7 years in microscopic

Asmaningsih Ninik AF-169 B Bagga Arvind AA-197

Cao Qi FP2-4

Chiou Yee-hsuan AB-151

Fang Xiao yan AD-100

Fang Xiao yan AK-106

Gheissari Alaleh FP5-2

Guan Na

Gulati Ashima

Gulati Ashima AH-201

Gunasekara Vindya

Gupta Punit

Kanda Shoichiro AA-164 KANEKO Kazunari

Kanitkar Madhuri FP3-4

Kim Pyung kil AJ-006

Lee So hee AA-182

Lim In seok AD-036

Lin Fangming SYM

Luchaninova Valentina N. AF-083 M

Namgoong Mee kyung AK-176

Nguyen Duc quang AA-192

Prasetyo Risky vitria AH-068

Rianthavorn Pornpimol

Sethi Sidharth

Sethi Sidharth kumar

Yeo Wee song AA-034

Introduction: The aim of this study was to evaluate the effectiveness of intravenous corticosteroid therapy when Henoch-Schönlein purpura (HSP) patients are unable to tolerate oral medications due to abdominal pain. Method: We retrospectively analyzed 111 children with a diagnosis of HSP (Mean age 6.9±2.3 years, Male: Female=55:56) from the years 2000 to 2003. One hundred and eleven children with HSP were divided into the two groups; 49 patients who were treated with only oral prednisolone (PL group) and 62 patients with oral prednisolone after intravenous dexamethasone (Dexa+PL group). Result: Palpable purpura was seen in all 111 patients (100%), abdominal pain in 55 (50%), and arthralgia in 65 (59%). There were no significant differences in the incidence of arthralgia between the two groups, but Dexa+PL group had significantly longer duration of fasting than PL group (0.7±1.2 vs. 0.02± 0.1 days, P<0.01) due to more severe and frequent abdominal pain (68% vs. 27%, P < 0.01). Serum albumin levels were significantly lower in Dexa+PL group than in PL group (4.0± 0.4 vs. 4.3± 0.4, P<0.01) . However, the development of nephritis (21% vs. 32%, P=0.98), the number of relapse (4% vs. 11%, P= 0.167) and persistent nephritis at last follow-up (12% vs. 16%, P =0.563) were not much different between the two groups. Conclusion: Intravenous dexamethasone followed by oral prednisolone may be a useful and effective therapeutic strategy in HSP children who cannot tolerate oral medications due to severe gastrointestinal manifestations such as severe abdominal pain or melena.AI-064: COMPARISON OF CLINICAL OUTCOME ACCORDING TO THE DURATION OF CORTICOSTEROID THERAPHY IN CHILDHOOD HENOCH-SCHÖNLEIN Introduction: The aim of this study was to evaluate whether the incidence of relapse or nephritis might be influenced by the duration of corticosteroid therapy in children with Henoch-Schönlein purpura (HSP). Method: We retrospectively analyzed 186 children with a diagnosis of HSP (Mean age 6.3±2.5 years, Male: Female=104:82) in two major hospitals in Ilsan, Korea from the years 2000 to 2007. One pediatric nephrologist from hospital A has used oral prednisolone in patients with mild symptoms and intravenous dexamethasone followed by oral prednisolone in those with severe symptoms (Group A, N=94). The other from hospital B has prescribed nothing in patients with mild symptoms and oral prednisolone in those with severe symptoms (Group B, N=92). Result: There were no significant differences in age, sex, body weight, white blood cell count, hemoglobin, hematocrit, platelet count, serum protein and albumin levels between the two groups. The incidence of abdominal pain (45% vs. 50%, p=0.557) or arthralgia (61% vs. 61%, p=1.0) also did not differ between the two groups. However, the duration of steroid therapy was significantly longer in Group A than in Group B (21. 8± 8.4 vs. 6.1± 7.4 days, p<0 .0001) and the cumulative dose of prednisolone was also higher in Group A than in Group B (404.4±248.2 vs. 105.1± 137.4 mg, p<0.0001). The development of nephritis was more frequent in Group A (23% vs. 10%, p=0.017), while the incidence of relapse was higher in Group B (10% vs. 23%, p= 0.017). Conclusion: The longer duration of steroid use was associated with the lower incidence of relapse, but the higher rate of nephritis development. Therefore, corticosteroids should be used carefully in a selected group of HSP children, and be tapered rapidly after acute symptoms are controlled.Introduction: Childhood enuresis is a common condition all over the world yet Malaysian parents rarely discuss it with their doctors. To understand the reasons for this, we interviewed parents of children who came for consultation. Method: A questionnaire was designed to determine parents': (i) views on the cause of their child's bedwetting, (ii) previous coping strategies, (iii) reasons for seeking medical consultation and (iv) perception of the impact of enuresis on their child Result: Thirty-two parents of children aged between 7 and 16 years attending the Enuresis Clinic consented to this study. Ninety-two percent of the children had more than 3 wet nights per week yet only 44% had ever seen a doctor. Deep sleep was thought to be a cause in 81% and "drinking too much" in 47% whilst genetics/familial in 19%. Only 6% thought their child would "outgrow" the problem. All parents had tried at least one of the 10 coping strategies itemized. The three most common practices were restricting pre-bedtime fluids (81%), waking the child to void (97%) and "lifting" the child (62%). Diapers were used in 41% and punishment in 25%. Reasons for seeking consultation included fear of the effects on the child (97%), fear of an underlying medical problem (65%), restriction of the child's social activities (56%), the child's embarrassment (59%) and tired of washing sheets (44%). Parents' perceived impact on the child included low self esteem (77%) and social stigma (63%). Conclusion: Despite less than half the families seeking medical consultation for this self-limiting disease, children with nocturnal enuresis in Malaysia and their families are clearly distressed by the problem and its psychosocial consequences, in particular the social stigma and perceived low self esteem. It is time that medical practitioners address these issues in a bedwetting child and offer appropriate therapy. Introduction: Our ability to provide safe and effective drug therapy for infants and children is often hampered by a lack of dosing information derived from careful, well-controlled trials and the limited database available concerning drug safety in this patient population. This problem was first articulated 40 years ago that infants and children were becoming "therapeutic orphans". It is important to note that many of such medicines are frequently used off-label in relation to dose, indication, age, and route of administration in infants and children. We approach the problem of off-label uses of drugs in Japanese children with kidney diseases. Method: We reviewed 90 drugs for children with kidney diseases derived from four Japanese references for pediatric nephrologists and revealed off-label uses of drugs in relation to dose, indication, age, and route of administration. Result: There were 6 of 90 drugs with no product license in Japan but 2 drugs with product license in US or EU. 44 drugs (49%) had lack of pediatric drug formulations. 11 drugs (12%) were not licensed use in children with the kidney diseases but were licensed use in children with other diseases. 69 drugs (77%) were not existing dosing information for pediatric patients. 59 drugs (66%) were not existing explicit statements that the safety and efficacy in children. Conclusion: Most drugs of the Japanese physicians' references entries have either no existing dosing information for pediatric patients or explicit statements that the safety and efficacy in Japanese children with kidney diseases. The progress made in the solution to the therapeutic orphan problem during 30 years in US and EU. We work for a general level of comfort with pediatric clinical trials and undertake the problem of off-label uses in Japanese children with kidney diseases.

Na Guan, Yan Chen, Hui-Jie Xiao, Jie Ding, Ji-Yun Yang

Introduction: To make a diagnosis of a girl with kidney subcapsular hydrops, abnormal urine analysis and hypertension. Method: Physical examination and laboratory investigations were analyzed. Result: A 5 years old girl was admitted because of kidney subcapsular hydrops, proteinuria without edema, and hypertension (130/94 mmHg) for 50 days. No trauma or familial hypertension history were provided. No hydrops was found before the age of 1 year. Urinary RBCs were 5-7/Hp and protein was 77 mg/kg/24 hr. The serum albumin was normal. Ultrasound examination revealed normal sized kidneys, increased echogenicity in both kidneys, and subcapsular hydrops on the upper pole of the right kidney connected with an old renal fissure. UCG and fundus examinations were normal. GFR of the right kidney was slightly decreased as compared to the left (65 ml/min vs. 67 ml/min, by DTPA scan). By puncture of hydrops, yellow clear fluid was drained, the analysis showed similar composition to that of original urine, so subcapsular urinoma was diagnosed. Urine collection from two kidneys separately was performed by cystoscopy; nonselective proteinuria of 1+ was found in urine from the right and 2 + from the left kidney. Analysis revealed urea 36.8 mmol/l, potassium 6.92 mmol/l, creatinine 0.42 mmol/l in the right kidney urine compared to urea 77.2 mmol/l, potassium 11.19 mmol/l, and creatinine 1.29 mmol/l in the left, which suggested that the right kidney function was compromised. According to proteinuria from both kidneys with microscopic hematuria, without edema and hypoalbuminemia, glomerulonephritis was diagnosed. Conclusion: The girl was diagnosed with glomerulonephritis and subcapsular urinoma. It was a rare case because of their co-incidence. Reasons for the hypertension, if caused by the glomerulonephritis or the pressure by subcapsular urinoma, as well as reasons for subcapsular urinoma need to be clarified during the follow-up.

Xiao Yan Fang, Hong Xu, Hong Yun Gao

Introduction: To evaluate the psychological conditions in children with chronic kidney diseases and the influence of their family. Method: Totally 46 patients were analysed, of which 38 children were primary nephrotic syndrome with normal renal function, 8 patients were with chronic renal failure (GFR<15 ml/min/1.73 m2). Six psychical questionnaires were used to evaluate the conditions: Child Temperament Questionnaire, Elsenc Personality Questionnaire (EPQ), Children,s Self-consciousness Checkilst, Child Behavior Checkilst (CBCL), Medical Coping Modes Questionnaire (MCMQ) and Home Environment Checkilst. Result: (1) Personality: 50% children age from 8-16 years old were introversive, and 40% children age from 3-7 years old were passive emotion; (2) Self-consciousness: Anxious score of children with chronic kidney diseases was lower than that of healthy children. In anxious group 40% children were introversive. All the children with abnormal conduct in CBCL were in anxious group. The mean period after treatment with steroid in anxious group was longer than that in non-anxious group. And the treatment in anxious group was more difficult than that in non-anxious group; (3) The behavior score was abnormal in seven children in CBCL; (4) In MCMQ, the parents of children with chronic kidney diseases would use the surrender or brave behavior; (5) In Home Environment Questionnaires: the scores of intimacy, perio knowledge, entertainment, morality and regulation were lower than that of healthy children. The knowledge score of