key: cord-0976074-kozxm2ub authors: Stevens, Jacob S.; Velez, Juan Carlos Q.; Mohan, Sumit title: Continuous renal replacement therapy and the COVID pandemic date: 2021-03-11 journal: Semin Dial DOI: 10.1111/sdi.12962 sha: 55daa9feff851de600cb7926af4144a06b02e3e3 doc_id: 976074 cord_uid: kozxm2ub Severe COVID‐19 illness and the consequent cytokine storm and vasodilatory shock commonly lead to ischemic acute kidney injury (AKI). The need for renal replacement therapies (RRTs) in those with the most severe forms of AKI is considerable and risks overwhelming health‐care systems at the peak of a surge. We detail the challenges and considerations involved in the preparation of a disaster response plan in situations such as the COVID‐19 pandemic, which dramatically increase demand for nephrology services. Taking careful inventory of all aspects of an RRT program (personnel, consumables, and machines) before a surge in RRT arises and developing disaster contingency protocol anticoagulation and for shared RRT models when absolutely necessary are paramount to a successful response to such a disaster. The ongoing SARS-Coronavirus-2 pandemic leading to widespread Coronavirus-2019 disease brings into the focus the paramount need for disaster planning within the nephrology community. 1 While the dramatic burden of respiratory failure and need for mechanical ventilation among patients with SARS-CoV-2 infection were recognized early in the pandemic and led to appropriate disaster planning, the recognition of the high rates of acute kidney injury (AKI) and subsequent need for renal replacement therapies (RRTs) in COVID-19 were delayed. 1 Early reports out of China appeared to have incomplete reporting of AKI with incidences as low as 0.5%-3%. 2, 3 Later reports including some from ICU cohorts reported wider variations in the incidence of AKI 5%-23%, but direct comparisons were limited by the absence of granular reporting on clinical information to compare the underlying severity of these cohorts. [4] [5] [6] [7] One large cohort in New York City (the hotspot early in the pandemic) reported an overall AKI incidence of 47%, with 31% stage 3 severity. 8 Similarly, a single-center report from New Orleans, another city heavily affected during the early days of the pandemic, reported 28% incidence of AKI with 55% requirement of RRT and 50% in-hospital mortality. 9 Differences in admission criteria and frequent absence of preadmission measures of kidney function limited the ability to draw precise conclusions on the burden of severe kidney disease. 8 A detailed systematic review and meta-analysis estimated the incidence of AKI among hospitalized patients to be as high as 17%. 10 The predominant mechanism DOI: 10.1111/sdi.12962 of renal injury appears to be acute tubular necrosis, as evidenced by pathological evaluation of urinary sediment microscopy, 11 kidney biopsies, 12, 13 and autopsies 14, 15 of patients with COVID-19 and AKI. Collapsing glomerulopathy (COVID-19-associated nephropathy, COVAN) and other podocytopathies have also been reported in individuals with African and other ancestry. [16] [17] [18] Whether there is a direct impact of SARS-CoV2 infection on the kidney remains uncertain with some investigators reporting on the identification of the viral particles on electron microscopy. 19 In the most severe disease, usually characterized by circulatory shock and ARDS requiring mechanical ventilation, severe AKI requiring RRT is quite common. It is now estimated that nearly 5% of hospitalized patients require some form of RRT for AKI, 10 while 20%-31% of critically ill patients develop indications for RRT. 10, 20, 21 Not surprisingly, kidney injury among critically ill patients with COVID-19 is also associated with a particularly poor outcome. This dramatic increase in demand in the face of unprecedented hospitalization rates and ICU censuses to accommodate the surge of patients has presented a unique challenge to the health-care system and in particular for nephrology services, as a surge in demand of this scale has not been seen outside of crush injuries from natural disasters. The absence of early estimates of the true burden of kidney injury created a situation where RRT resource planning did not occur ahead of time. It should be noted that this increased need for RRT does not include the increase in dialysis-dependent patients with end-stage kidney disease needing hospitalization and continued maintenance RRT. Providing RRT both in the ICU and outside is a resource intense procedure that requires significant capital investments (dialysis machines), consumables (filters and blood lines), dialysate fluids (either continuous produced or in pre-packed sterile bags), and health-care workers (dialysis nurses and technicians) with appropriate advanced training. As a result, RRT is dependent on a robust supply chain that had not previously been faced with such a rapid, sustained, and widespread increase in demand. As an example, the projected shortfall in continuous renal replacement therapy (CRRT) machines across just six states in the United States with a COVID surge was nearly 1000 machines. 22 At the height of the first COVID-19 surge in NYC, the number of patients with indications for RRT exceeded the availability of CRRT resources. 1 Different strategies for delivering RRT to these critically ill patients needed to be explored, and factors that influenced our decisions to adopt different strategies are summarized in Table 1 . Given the paucity of devices and the challenges of intermittent hemodialysis (HD) in hemodynamically unstable patients, several large academic centers shifted to protocols that allowed devices to be shared between patients resulting in the use of traditionally continuous therapies in a non-continuous manner-an approach that has previously been referred to as either prolonged intermittent renal replacement therapy (PIRRT) or accelerated veno-venous hemofiltration. 23 One approach to conserve commercially available therapy fluid that was utilized by some during the pandemic surge is a nomogram to prescribe a specific number of 5 L therapy fluid bags per patient per day rather than prescribing only in mL/min. 1 There are a number of unique factors to take into consideration when reorganizing a CRRT program as we have described so far. First is the hypercoagulability seen in COVID-19 disease, and the challenges this places on a vulnerable supply of cartridges and blood products and trying to minimize nursing to patient contact time to protect nurses from occupational COVID exposure. One group de- Figure S1 ). This algorithm underscores the extreme hypercoagulability in this group of patients and the unique demands that it places on CRRT resource consumption and RN workload in an already vulnerable system. 32, 33 Line placement site is another additional factor that needs careful consideration. Given the spatial complexities with proning patients, internal jugular dialysis access sites are preferred over femoral or subclavian sites. 35 The CRRT blood circuit is disconnected from the patient during the actual process of proning and supinating patients in order to prevent kinking and wrapping around the advanced airway. While there are anecdotal reports of using blood line extension tubing in order to allow the CRRT machine to remain outside of the ICU room to minimize nursing exposure and conserve PPE, there are no studies examining whether this leads to increased machine alarms, performance of pressure monitors, and filter clotting. It is for this theoretical concern that while our institution did use therapy fluid extension lines to allow for therapy fluid bag exchanges to occur outside of the patient room, we actively decided not to pursue blood line extenders given the high rates of clotting we were already experiencing. Of note, certain device cartridges already incorporate extended tubing to facilitate use with citrate anticoagulation, which would also lend themselves well to placing the CRRT device outside the patient rooms. Among survivors, careful monitoring for renal recovery is paramount, not only during the index hospitalization but even after discharge given that survivors experience continued renal recovery. While definitions for renal recovery vary substantially, it is usually heralded by an increase in urine output, which is the best predictor of renal recovery and successful discontinuation of RRT. 28, [40] [41] [42] The reported volumes of UOP that best predict recovery also vary 40 What, if any, impact dialysis-dependent AKI will have on the long-term prevalence of ESKD or the rates of renal recovery among patients who remain dialysis-dependent for longer duration remains to be seen. 43 Prior studies have found that acute tubular injury (ATN) on biopsy is one predictor of renal recovery. 44 The high rates of renal recovery now being seen in COVID-19 AKI survivors are in line with the predominant pathological finding of ATN previously described, where the authors describe a pattern of tubular injury that appears less severe than the clinical phenotype and has been described as a 49, 50 and by 30 days after discharge, 43% of patients who were RRTdependent at discharge had recovered renal function. 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