key: cord-0801681-44timla8
authors: Bodington, Richard; Kassianides, Xenophon; Bhandari, Sunil
title: Point-of-Care Testing Technologies for the Home in Chronic Kidney Disease: a Narrative Review
date: 2021-04-20
journal: Clin Kidney J
DOI: 10.1093/ckj/sfab080
sha: 6439f8f92afbeea8af8ff036f696ada18bee80af
doc_id: 801681
cord_uid: 44timla8

Point of care testing (POCT) performed by the patient at home, paired with eHealth technologies, offers a wealth of opportunities to develop individualised, empowering clinical pathways. The non-dialysis dependent chronic kidney disease (NDD-CKD) patient who is at risk of, or may already be suffering from, a number of the associated complications of CKD, represents an ideal patient group for the development of such initiatives. The current COVID-19 pandemic, and drive towards shielding vulnerable individuals, has further highlighted the need for home testing pathways. In this narrative review we outline the evidence supporting remote patient management and the various technologies in use in the POCT setting. We then review the devices currently available for use in the home by patients in five key areas of renal medicine: anaemia, biochemical, blood pressure, anticoagulation and diabetes monitoring. Currently there are few devices and little evidence to support the use of home POCT in CKD; while home testing in blood pressure, anticoagulation and diabetes monitoring are relatively well developed, the fields of anaemia and biochemical POCT are still in their infancy. However, patients’ attitudes towards eHealth and home POCT are consistently positive and physicians also find this care highly acceptable. The regulatory and translational challenges involved in the development of new home based care pathways are significant. Pragmatic and adaptable trials of a hybrid effectiveness-implementation design, as well as continued technological POCT device advancement, are required to deliver these innovative new pathways that our patients desire and deserve.

Point-of-care-testing (POCT) in healthcare refers to the analysis of patient samples beside, or close to, the patient. POCT can be used in three settings; by a healthcare professional (HCP) in a healthcare setting, by a HCP in the patient's home, or by the patient in their own home. The reason for POCT in the former two settings is to reduce the time between test and decision, for economic gain (primarily in emergency/acute medicine the time from admission to a decision on disposition) (1) . To this end POCT has been shown to be effective, at least in the emergency department and ambulatory care clinic (1) . However improvements in healthcare processes do not reliably translate into meaningful changes for patients; the effects of introducing POCT to a clinical process can be complex and are often not properly evaluated subsequently (2) .

The outcome focus when POCT is used at home by the patient is different. NHS England make it clear in their 'long term plan' that health innovation and development of new models of care must be accelerated to give patients greater control over their care (3, 4) . There is increasing acknowledgement of patients as 'experts by experience'; allowing them a role in the management of their conditions is likely to lead to better concordance and improve health outcomes. POCT performed by the patient at home offers a wealth of opportunities to develop individualised, empowering clinical pathways; the non-dialysis dependent chronic kidney disease (NDD-CKD) patient who is at risk of, or may already be suffering from, a number of associated complications of CKD, represents an ideal patient group for the development of such initiatives. Renal medicine physicians have a track record of early adoption of such technologies as exemplified by widespread use of the 'PatientView' web portal (5) .

Remote patient management presents a potential opportunity in renal medicine to improve clinical outcomes and patient quality-of-life whilst boosting patient engagement with their disease management (6) . This has been demonstrated in studies in peritoneal dialysis (PD) and home Such results underline the benefit of remote patient monitoring and the rationale behind the movement towards chronic disease home-based management. The majority of eHealth technology already exists and could be readily applied to the care of patients; the exception is the POCT technologies themselves (12) . POCT devices can be incorporated into eHealth solutions and patients managing their conditions with a POCT device have greater motivation to be involved in the management of their condition and greater confidence in their doctors; additionally in the field of diabetes significant improvement in clinical outcomes such as glycaemic control have been demonstrated by patients who use a home POCT device (2) . However devices and their associated pathways need to demonstrate accuracy, validity and non-inferiority to traditional care (2) . eHealth and home POCT introduce a number of potential safety concerns over traditional care, such as data security and patient and staff training; extreme care should be taken when any eHealth and POCT intervention is used in place of traditional care without full validation (17) . Consequently WHO have issued their ASSURED guidance to aid in the development of POCT devices and their pathways ( Table   1 ) (18) .

POCT, as with laboratory testing, is subject to several international standards to ensure quality. It is paramount that quality assurance be maintained alongside efficient record keeping and results interpretation (19) . Continuous and ideally bidirectional flow of data between potentially hundreds of POCT devices, the laboratory information system and the EPR should be engineered to make this possible (19, 20) . A number of programmes, such as POCcelerator (Siemans healthineers) and RALS Web 3 (Alere Informatics), have been designed to fulfil these roles of data collection and review, internal quality control (IQC), external quality assurance (EQA) and, via intelligent dashboards, datadriven decision making. Systems can be further enhanced through the use of 'machine learning' and programmable alerts as currently seen in the analysis of implantable loop recorders in cardiology (21) . The vast amount of data analysed by such systems, assessing the regular testing of hundreds of patients, presents an ideal opportunity for the discovery of new insights via the use machine learning/ artificial intelligence (22) . ICT alone is however inadequate to ensure the quality of such pathways; appropriately trained staff need to be vigilant in reviewing results and communicating concerns regarding device and patient factors, while ensuring sufficient patient training on the use of their devices. Hence the work involved in the implementation of a new POCT pathway can appear monumental and involves a transformation of diagnostic services and care provision (23) . The UK Medicines and Healthcare Products Regulatory Agency (MHRA) have recently published guidance on implementation of POCT solutions (24). Advice includes the creation of specialist POCT committee composed of laboratory staff, clinicians, specialist nurses, nursing staff, IT specialists, pharmacists and finance specialists responsible for the overall service, IQC and EQA. Identifying all stakeholders early in the implementation of a POCT pathway will allow topics such as record keeping, accreditation and maintenance to be addressed whilst troubleshooting logistic and equipment problems (24). Integration of POCT pathways into existing systems is often expensive and difficult and many initiatives suffer from a lack of dedicated support (19) . Without specialist support POCT pathways lack quality control, become isolated and are liable to become unsafe and ineffective (19) .

Thousands of POCT devices have been developed in academic labs; a minority are able to analyse untreated samples and involve processes that make them suitable for home use (12) . A small percentage of these devices have been commercialised and only a few of these have been successfully evaluated and integrated into clinical practice (12) . Devices that are suitable and licensed for home monitoring make up a smaller proportion again (12) . Additionally, large healthcare organisations are slow to change routine clinical practice and care pathways must be optimised to gain the maximum benefit from a POCT device (2) . Despite this the global POCT market is worth over USD $28 billion with an estimated five year compound growth rate of approximately 9% (18) .

Home POCT has been integral to diabetes care for years and other fields, namely that of anticoagulation, have established use of home testing pathways (25) . CKD is a common and longterm condition with high associated healthcare costs; innovative pathways including home POCT by patients have the potential to improve these patients' health status and allow them to understand and take greater control of their health (26) . The POCT devices themselves are the weak link in the development of such pathways and their review in the field of renal medicine has been neglected. This article will outline the technologies present for POCT at home and review the currently available devices relevant to renal medicine and the evidence supporting their use.

A great amount has been written about the design and function of the multitude of POCT devices that have been developed; these have been the subject of numerous detailed reviews and are beyond the scope of this article (2, 12, 27) . Table 2 briefly summarises the technologies used in POCT to add context to the later discussion (25, (28) (29) (30) (31) (32) (33) (34) (35) .

A number of the markers of interest in CKD are challenging to measure via POCT; for example the complexity of creatinine's specimen matrix makes it prone to many confounders and the haemolysis associated with finger-pricking makes potassium measurement almost impossible via this method (36). Additionally CKD poses a number of additional challenges to the developers of POCT devices over and above those experienced in the general population. Fluctuations in volume status and therefore in haematocrit (Hct) are common in CKD due to dialysis or the use of diuretics; POCT devices that use finger prick samples are especially prone to this confounder due to the contribution of interstitial fluid. Variations in Hct will clearly affect haemoglobin calculation in applicable POCT devices but have also been shown to affect the calculation of other parameters such as glucose concentration and INR (37,38). Readings from POC devices measuring glucose and creatinine have also been shown to be confounded by fluctuations in potassium, calcium, albumin, urea and uric acid, all of which are frequently seen in CKD (39, 40) .

In this section we will discuss the small number of devices available and appropriate for patient use in home monitoring and the evidence surrounding their use. Popular and adaptable POC devices such as the iSTAT (Abbott Point of Care) will not be discussed as they are too bulky and expensive for widespread home use. Devices in development that are yet to achieve authorisation for either professional or home use, fall outside the scope of this current review and will not be discussed. 

It is well established that appropriate management of renal anaemia by the use of iron supplementation and erythropoietin stimulating agents (ESA) improves CKD patient's quality of life, lessens symptom burden and improves aspects of prognosis (41) (42) (43) . Enabling this care to take place in the home is attractive to physicians and patients.

Luma (Entia Ltd.) is a 78x83x52 mm device weighing 96g with a Conformité Européenne (CE) mark for home use in the measurement of Hb (44) . The device uses a microcentrifuge on 4-8 μl capillary blood in a reagent free cuvette for a measure of haematocrit followed by photometric absorptiometry to calculate haemoglobin. A smart-phone app is available to use with the device for data storage, symptom tracking, reminders and the display and transmission of Hb results. In preliminary studies of 376 paired capillary and venous blood samples the device has been compared to lab based Hb measurement (Beckman Coulter LH750). The Entia device measurements showed a high degree of correlation with the LH750 (r=0.99) with a coefficient of variation (CV) of 7.1% (unpublished data, Entia, UK)( Table 3 ). The device has been used successfully in the iron-deficiency anaemia population and currently Luma is undergoing deployment at a number of NHS trusts to assess the utility of the device in the ESA prescribed NDD-CKD population with studies yet to report.

The fact that this device is the only haematology POCT device on the market for home use makes it a promising candidate for wider use within healthcare services once service evaluations are complete.

The company are also developing a similar device for monitoring the full blood count (FBC) aimed at the oncology market. Table 3 ). The authors are unaware of any use of this device by patients. However the HemoCue WBC DIFF, a similar if slightly larger and prohibitively expensive device (> GBP £4000), using macroscopically similar microcuvettes has been used by patients in their own home (25, 47) . In a trial of 14 breast cancer patients undergoing chemotherapy, 42 HemoCue results were compared to lab measurements within three hours (47) . The mean difference (MD) between methods for white cell count (WCC) was 0.36x10 9 /L (standard deviation (SD) 1.01, correlation (r) 0.86, limits of agreement (LOA) -1.61x10 9 /L to 2.34 x10 9 /L (7.1% of measurement pairs outside of LOA) (47) . The LOA were wider than considered clinically acceptable and the device was not considered suitable for use at home (47) . In another oncology study 60 outpatients and 22 in-patients on active treatment were asked to test themselves using the same device, this time in hospital only, with results compared to lab FBC (25) . Fifty-seven percent of patients were able to conduct a self-test on this machine after a single demonstration with no further help needed; after follow-up guidance 96% were judged able to test in their own homes (25) .

Ninety percent of patients were successful in filling and placing the cuvette on their first try with no difference in success observed between younger and older individuals (25) . All results were within the predefined acceptable range of ± 1x10 9 /L for WCC (25) . The device was considered to be reliable and clinically useful at the lower range of WCC and neutrophils with self-testing (25) . In a further study of 50 patients self-testing after a single teaching session, high correlation between nurse and patient obtained results were demonstrated (R 2 = 0.921, p< 0.001), but with 18% of patients unable to achieve a result with the device, most commonly due to air in the cuvette (48)( Table 3 ). It is important to specify that, although the cuvettes and sampling techniques are superficially similar, it cannot be assumed that the results for this device can be applied to the HemoCue Hb systems or are applicable to CKD patients. Neither device is authorised for home use.

Whilst a number of other devices for professional use, small and simple enough for potential use at home such as DiaSpect (EKF Diagnostics) have been shown to be useful and reliable in the hands of HCPs, none have been evaluated for patient use (Table 3 ) (48) . Furthermore, even for the Luma and WBC DIFF devices, the integration of home POCT haematology devices into clinical care has yet to be demonstrated and there is significant regulatory and economic hurdles to overcome before this can be done in addition to issues about the transfer of these results onto hospital EPR systems.

Good blood pressure (BP) control is one of the key interventions that can slow renal decline (49) . It follows that home BP monitoring is one of the most important monitoring devices in nephrology;

devices that can aid effective BP control have a great potential to improve renal outcomes in NDD-CKD patients. Ambulatory blood pressure monitoring (ABPM) is the preferred method for diagnosing hypertension (50) . However the principle advantage of ABPM, multiple readings especially at night, is the main reason that the devices may not be acceptable to patients; they are uncomfortable and disturb sleep (50) . ABPM also has costs in terms of time and money associated with travel to and from hospitals for fitting and device drop-off (50) . Home blood pressure monitoring (HBPM) is a more acceptable alternative to ABPM with similar benefits over clinic monitoring and consequently it is also endorsed in guidelines for both confirmation of diagnosis and in the monitoring of hypertension (51) .

BP monitors can be defined as cuff and non-cuff based; cuffed devices can be designed to be fitted to the upper arm, wrist or finger (27) . Few studies have rigorously assessed BP monitoring devices against each other despite significant differences between commercially available models having been described (52) . No significant differences in mean BP were noted when several fully automated oscillometric upper arm devices, meeting American National Standards Institute (ANSI) standards, were compared to a standard manual mercury sphygmomanometer or a manual aneroid sphygmomanometer in a review of the literature (52) . However a significantly higher mean BP was noted with a fully automated cuffed wrist device compared to the mercury sphygmomanometer (153 ± 28 /87 ± 18 vs. 137 ± 20 /80 ± 11 mmHg, p<0.001) (52) . Meanwhile a finger BP cuff device was noted to give significantly lower readings than a mercury sphygmomanometer (114/69 vs. 129/78 mmHg, p<0.05) (52) .

Non-inflating wristwatch-like devices, such as BPro (HealthSTATS International), utilising a pulse wave acquisition system via modified applanation tonometry to acquire arterial radial pulse waves and calculate BP have been shown in several studies to correlate well with upper arm BP measurement but remain prohibitively expensive (> GBP £2000) (Table 3) (27, 53, 54) . Fully cuff-less BP monitoring devices; able to calculate BP based on pulse transit time, currently have limited validation data, in addition to a high calibration failure rate and frequent need for recalibration, although the Freescan (Maisense) device has achieved ANSI validation for non ambulatory use (Table  3 ) (17, 27, 55) . Bard and colleagues have comprehensively reviewed these technologies, their advancement and limitations (56).

In patients suffering hypertension alone remote BP monitoring has been shown to improve BP control and treatment adherence (57). The evidence is less clear in those with CKD and hypertension. A systematic review on the subject of remote home management in dialysis dependant or transplanted CKD patients assessed three randomised studies that focussed on BP control (26) . No significant difference in systolic or diastolic BP was noted in the patients offered remote monitoring of their BP verses standard care (26) . However in dialysis dependant patients remote monitoring did allow optimisation of weight gain and reduced ultrafiltration volumes, albeit in a small sample size (n= 120) (26) . Despite this apparent lack of effectiveness patients and nephrologists consistently showed a positive attitude towards remote monitoring with 96% of patients stating that they would like to continue using their BP monitor in one study (26, 58) .

Similarly, in another study 91% of 601 CKD patients assigned to home monitoring completed a year of monitoring with an average of 14.2 completed virtual clinics per year and 14.9 BP readings per month (59).

The use of BP devices at home is well established but the associated eHealth technologies are only just emerging. HBPM is effective in hypertensive patients and shows a lack of efficacy in dialysis dependant patients, however there is a lack of evidence in NDD-CKD patients. Currently a fully automated oscillometric upper arm BP monitor with wireless connectivity to a mobile app for the storage and transmission of results appears to be the most reliable, acceptable and cost-effective method of monitoring. However, with ongoing development wristwatch devices and completely cuff-less devices are likely to become increasingly prominent in hypertension monitoring (56).

Monitoring of electrolytes, urea and creatinine are important in the routine care of CKD patients and the benefits of the home monitoring of these parameters are easy to imagine. However in this field there are currently very few devices available that are potentially suitable, and none that are currently authorised, for home use.

The small and user-friendly StatSensor Xpress Creatinine (Nova Biomedical) is 91 x 58 x 23 mm and weighs 75g, making it potentially suitable for home use, with acceptable concordance to lab based systems at creatinine values <600 µmol/L ( 

Diabetes Mellitus is the most common aetiology of CKD and good glycaemic control is important factor in renal disease progression (64) . POCT has long been part of the care of patients with diabetes; glucose meters have the largest share of the POCT market and dominate the home testing market (28) . There are a large number of small, light and simple to use glucose meters commercially available that are licensed for use at home; evidence supporting their use exists in the general diabetes and CKD-diabetes populations (65) (66) (67) .

Continuous and flash continuous glucose monitoring (CGM and FGM respectively), which measure interstitial glucose concentration either continuously (CGM) or on patient-demand (FGM) have been shown to be effective in CKD patients. The DIALYDIAB pilot study used the iPro2 (Medtronic) to monitor glycaemic control in 15 HD-dependent diabetic patients. Patients were followed-up for 12 weeks with CGM taking place in weeks 6 and 12 after the device was fitted by a nurse specialist; the study concluded that CGM lead to more frequent changes in treatment regime resulting in improved glycaemic control and decreased frequency of hypoglycaemia (68) . Despite performance of quality of life assessment, the impact of such regime on quality of life was not commented on in the study (68) . A further pilot study assessed the same patient group (n=28 Type II diabetes patients using the Navigator device; Abbot). CGM-facilitated-change in insulin management at the beginning of the trial lead to a significant decrease in HbA1c at 3 months (8.4±1.0% to 7.6±1.0%; p<0.001) and a significant decrease in hyperglycaemia (69) . A randomised trial comparing CGM with self-monitoring of blood glucose (n=30; CKD G3) indicated that the proportion of time hyperglycaemic in CGM patients decreased from baseline to week 6 (65.4±22.4% to 54.6±23.6% (p=0.033)) with no significant change in time hypoglycaemic. Both self-monitoring and CGM were successful in improving glycaemic control (HbA1c baseline 9.9±1.2; end of trial: 9.0±1.5% (p<0.001)) with no difference between the two modalities (p=0.869) (70) . Within the caveats of the small and shortterm studies presented CGM appears to afford the same benefits to diabetic CKD patients as to the general diabetic population (69, 71) . The analytical performance of two popular CGM devices for home use are summarised in table 3.

The integration of smart-phones with blood pressure and glucose monitoring devices is particularly key in diabetes care. Diafit is a smart-phone app that allows integration and storage of diabetic patients' dietary intake, physical activity (via integration with a fitbit), medication use, blood glucose values (via Bluetooth upload or manual entry) and general well-being (72) . The physician can view this information and communicate with the patient via the app. Although such an app represents no technological innovation increased usability and effective integration of data can deliver significant benefits for patients. Similar innovative apps may prove vital to realising the greatest gain from home testing pathways.

Anticoagulation is commonly required in CKD patients and anticoagulants are among the most prescribed drugs in this patient group (73) . However despite the standard use of direct oral anticoagulants (DOAC) in the general population, the pharmacodynamic properties of these drugs limit their use in advanced CKD, with multiple guidelines suggesting warfarin to be the safest choice in patients with creatinine clearance <15 ml/min/1.73m 2 (74) . As CKD and declining eGFR represent a paradoxical state of hypercoagulability with increased haemorrhagic risk, international normalized ratio (INR) home monitoring with POCT devices represents an attractive prospect (75) . (Table 3 )(76), and a potential reduction in bleeding rates (n=128, home monitoring vs. usual care: incidence of bleeding at 3 months with home monitoring: 15%, with usual care: 36%; p<0.01) (77) . A later RCT (n=2922) suggested that there was no difference in the time to first event (stroke, major bleeding episode, or death) between participants using home devices and those being monitored traditionally (hazard ratio, 0.88; 95% confidence interval (CI), 0.75 to 1.04; p=0.14) (78) . It did however demonstrate a significant improvement in satisfaction with care and quality of life in patients in the home monitoring group (p=0.002 and p<0.001 respectively) with these results ratified more recently (78, 79 (Table 3) , however device usability data and patient related outcomes were not reported (80, 81) .

The positive impact of coagulation home monitoring has been highlighted in a recent Cochrane review (28 RCTs, n=8950) ; despite low quality of evidence a signal of improved quality of life and reduced rate of thromboembolic events was seen with home monitoring (82) . Sharma and colleagues also performed a systematic review and economic evaluation surrounding the use of these devices (26 RCTs, n=8763) which despite clinical heterogeneity amongst the trials indicated improved time in therapeutic range with self-testing (weighted mean difference: 4.4% (95% CI: 1.71-7.18) p=0.02) and cost-effectiveness given the positive effect on thromboembolic event incidence (83) . Self-monitoring was also deemed to be cost saving with a reported net saving of £112 million in the NHS if 10% of the current 950,000 patients on vitamin K antagonists were to switch to home POC coagulation monitoring (84) . No studies specific to CKD have been carried out with Xprecia Stride or CoaguCheck. The positive trends exhibited with home monitoring of anticoagulation via the use of POCT could reasonably be transferrable to the CKD population but this remains to be proven.

CKD is a common and increasing health problem with high associated healthcare costs (26) . Remote home management, made possible through eHealth pathways and suitable POCT devices, have great potential to improve health outcomes for these patients and help them understand their condition and engage more with their care (26) . Such pathways are highly in keeping with numerous steering committee's forward plans (3, 4) . Patient motivation is a key part of CKD management and eHealth has already shown itself to be an effective tool in CKD patients; however the development of the POCT devices themselves have been the weak link in this innovation and have held back the development of increasingly integrated pathways (14) . Home self-testing using a POCT device is still in its infancy in all fields other than diabetes care, hypertension and anticoagulation monitoring; in haematology and electrolyte measurement few devices suitable for home use exist and evidence supporting their use is absent. However, where the devices are well developed, evidence shows the benefits of their use both in terms of clinical and patient centred outcomes. Patients' attitudes towards eHealth and home POCT are consistently positive and physicians also find this care highly acceptable (14, 26, 85) . POCT devices need to be valid, operate with minimal user involvement and be cost-effective (12) . New care pathways need to be created, utilising eHealth, to maximise the benefit of such devices; these pathways must be safe, non-inferior and effectively integrated within the wider healthcare system. It seems prudent to incorporate patient smart-phones into these care pathways due to the wealth of ICT they contain which can supplement, or even allow the phone to become, a POCT device. Such integration enables interventions to become scalable across socioeconomic groups (72) .

Currently there are few devices and little evidence to support the use of home POCT in CKD; regulatory and translational challenges loom large. Evidencing the benefits of these care pathways, and the subsequent calculation of financial reimbursement are challenging. Pragmatic and adaptable trials of a hybrid effectiveness-implementation design, as well as continued technological POCT device advancement, are required to deliver these innovative new pathways that our patients desire and deserve (17, 25) . The need for this change has been greatly enhanced by the current COVID-19 pandemic.

This paper has not been published previously in whole or part. XK and RB declare no conflict of interest. SB is working on a project funded by an Innovate UK grant with Entia Ltd. This work was written independently and received no funding. (25, 26) .

Simple in design, use and manufacture; therefore cheap and well suited to use in resource limited settings (18) . Portable and easily disposable. Can detect >10 analytes simultaneously.

Subjective nature of reagent colour change prone to interpretation error. Multi-reagent strips can be misread due to misalignment with the key. Excessively dilute or concentrated urine may lead to errors in interpretation.

-Siemens Multistix (10 parameter urinalysis) -Bayer Ketostix (single parameter ketone urinalysis)

Composed of a number of abutted pads mounted on backing card. Sample applied to sample pad and drawn by capillary action through several pads and into contact with reagents and a label to produce a visible marker of detection. Most read after 5-15 min; display a control line (as proof of assay validity) and 1 or more test lines allowing qualitative or semi-quantitative estimation of analyte/s. Multiplexing possible by the use of multiple test strips or multiple test lines on the same strip. Colorimetric, fluorescent, electrochemical or enzymatic detection systems designed (26) . Can be read by eye or via a reader tool which may improve accuracy of quantification (18) .

As per dipsticks can be multiplexed to detect >10 analytes simultaneously. Simple, portable, easily disposable and low-cost.

Label in LFA should be detectable over a large and clinically useful range, have low non-specific binding, be stable in storage, lowcost and be easily conjugated with its biological compound without losing activity (18) . Sensitivity an issue.

-Clearblue pregnancy test (urine human chorionic gonadotropin) -SD Biosensor Lateral Flow Test (saliva SARS-CoV2)

Microfluidic channels are created by printing hydrophobic or hydrophilic material onto paper. Screen printing widely used. A μPAD made from a few stacked layers of patterned paper is able to Paper's 3D fibrous structure facilitates pump free wicking, and is fluid permeable so allows As with LFA sensitivity an issue, a problem particularly predominant in microbiological assays.

Beginning to transition from research to commercial applications: no devices store reagents and allow the controlled wicking of fluids to create a multiplexed device and allow multistep analysis or quantification of analytes (12) . The analyte is labelled and read, by colorimetric or fluorescent methods as per the LFA (18) . Can be paired with electrochemical or potentiostat readers. These can be bought for USD $90 and provide high sensitivity for the reading of multiplexed μPADs (26).

creation of multi-layered devices with vertical as well as horizontal flow (12) . Paper can act as a microcuvette for the storage of reagents and can be machined, by printing or other methods, in similar ways to silicone for a fraction of the cost (23) . Screen printing technique and is inexpensive and readily reproducible (18) .

Enzyme, silver or gold based amplification schemes can be used to increase the sensitivity a μPAD or LFA but these only recently practical without additional user steps (12) .

in widespread commercial use.

CardioChek Home Use Analyser (serum glucose, high density lipoprotein (HDL), total cholesterol and triglyceride)

Microfluidic devices that use pressure, centrifugal, electrokinetic or acoustic, in addition to capillary, driving forces (26) . Based on silicone, glass or polymer base and requiring pumps, valves, microfilters and containers of regent, which have proven expensive and challenging to miniaturise (12, 23) .

Innovation continually reducing the price and need for user input into such devices. Potentially able to overcome some of the limitations of LFA and μPAD.

Components formally expensive, challenging to miniaturise and required additional user steps (thereby reducing usability and introducing error).

Abbott Point of Care iSTAT (multi-cassette device allowing analysis of various serum parameters, eg. creatinine)

Analyse <100μl of untreated samples inside a microcuvette or electrochemical microcell with the reagents required for analysis stored in dry form within the microcell (18) . For example, upon the addition of untreated blood to a microcell, the reagents facilitate the lysis of undesired cells and staining of target cells. The sample is subsequently imaged and differential cell counts made via image recognition technologies (12, 19) .

Does not rely on the use of appropriate labels. Able to perform high quality analyses not currently possible in other devices (eg. 5-part full blood count differentiation and quantification).

Limited by the ability of the reagents to be stored effectively within the cell and also by the need for electricity, increasing complexity and expense.

-Radiometer Medical HemoCue WBC DIFF (serum full blood count and 5 part differential).

-Entia Luma (serum haemoglobin)

Design depending on use. Devices should require minimal input from the user and be fabricated as to be almost unnoticeable to the wearer. Continuous glucose meters consist of a With the exception of wearable glucose meters, wearable POCT devices remain in the microneedle inserted into the subcutaneous tissue connected to a wearable electrochemical potentiostat which allows monitoring of glucose in the interstitial fluid (12) . Sweat analysing devices have been developed using microfluidic microchips and printed electrodes to measure analytes by potentiometry, chronoamperometry and voltammetry (1). Sweating is induced by an iontophoresis interface using heaters or pilocarpine based hydrogels (1). Devices can be read and analysed using a smart phone camera and app (1).

flexible, waterproof substrates such as thin silicone layers. pH sensing decals have been fabricated for USD $0.08 making single use application possible (28) .

potentiometric or amperometric sensors have traditionally been expensive (28) . Many devices affected by temperature, pH and humidity and require advanced calibration so are not currently suitable for clinical use (12) .

early stages of development, interest primarily focussed on military and sports science applications.

-Abbott Diabetes Care Freestyle Libre (interstitial fluid glucose) -SwEatch platform (sweat sodium and potassium)

Smart-phones contain processing, data acquisition, display and transmitting technologies that can integrate with and supplement home POCT devices; apps may allow the smart-phone to act as a POCT device alone. There are the three levels of smart-phone involvement with POCT. 1. Selfcontained POC devices receive, process and analyse a sample, the smart-phone then acts to receive, store and send the data produced (30).

Use of hardware that supplements the abilities of a smart-phone. Eg. An optics system that illuminates a test strip with the smart-phone acting as sensor (via the camera) and analyser (30). 3. Use of systems and sensors available on the smart-phone alone; the phone becomes the POC device.

Increasing smart-phone integration has benefits in terms of ease of deployment, use and low cost (13) . The information and communications technology in smart-phones is robust and well developed. May allow better integration into user's life.

Concerns regarding data security. Issues of integration with varying smart-phone models.

-HemaApp (application estimates haemoglobin via the phone's flash, infra-red emitter and camera alone) -Holomic rapid diagnostics reader (HRDR-200) (optomechanical attachment and smart-phone app that allows the phone to act as a LFA reader) 

Impact of pointof-care panel tests in ambulatory care: a systematic review and meta-analysis

The state of point-of-care testing: a European perspective

The NHS long term plan

NHS England's five year plan

The role of patient portals in enhancing self-care in patients with renal conditions

Remote Patient Management for Home Dialysis Patients

Remote Treatment Monitoring on Hospitalization and Technique Failure Rates in Peritoneal Dialysis Patients

MO029CLINICAL AND SOCIAL ADVANTAGES OF REMOTE PATIENT MONITORING IN HOME DIALYSIS | Nephrology Dialysis Transplantation | Oxford Academic

Can Remote Patient Management Improve Outcomes in Peritoneal Dialysis?

Telenephrology with Remote Peritoneal Dialysis Monitoring during Coronavirus Disease 19

The COVID-19 infection in dialysis: are homebased renal replacement therapies a way to improve patient management?

From Point-of-Care Testing to eHealth Diagnostic Devices (eDiagnostics)

Telehealth by an Interprofessional Team in Patients with CKD: A Randomized Controlled Trial

A randomized trial of a multicomponent intervention to promote medication adherence: the teen adherence in kidney transplant effectiveness of intervention trial (TAKE-IT)

Ehealth interventions for people with chronic kidney disease. Cochrane Database Syst Rev

Intervention and evaluation of mobile health technologies in management of patients undergoing chronic dialysis: Scoping review

eHealth in kidney care

Point of care testing: The impact of nanotechnology

Practical challenges related to point of care testing

A Practical Example of PoCT Working in the Community

Integration of novel monitoring devices with machine learning technology for scalable cardiovascular management

Covid-19, big data: how it will change the way WE practice medicine

Medicines and Healthcare Products Regulatory Agency. Management and use of IVD point of care test devices

Patient self-testing of white blood cell count and differentiation: A study of feasibility and measurement performance in a population of Danish cancer patients

Remote home management for chronic kidney disease: A systematic review

Recent advances of biosensors for hypertension and nephrology

Existing and Emerging Technologies for Point-of-Care Testing

Quality targets in dipstick urinalysis

Endogenous factors modified by hemodialysis may interfere with the accuracy of blood glucose-measuring device

Point-of-Care Measurement of Serum Creatinine in the Intensive Care Unit. Ren Fail

Quality of life and anemia: the nephrology experience

Renal association clinical practice guideline on Anaemia of Chronic Kidney Disease

Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease

Falling Usage of Hospital-Based Emergency Care During the COVID-19 Pandemic in the UK

Systematic comparison of four point-of-care methods versus the reference laboratory measurement of hemoglobin in the surgical ICU setting: a cross-sectional method comparison study

HemoCue photometer: a better alternative of hemoglobin estimation in blood donors?

Preliminary Results from a Prospective Study Comparing White Blood Cell and Neutrophil Counts from a Laboratory to Those Measured with a New Device in Patients with Breast Cancer

Home Testing of Blood Counts in Patients with Cancer

Blood Pressure Control, Proteinuria, and the Progression of Renal Disease

Patient perceptions of ambulatory blood pressure monitoring testing, tolerability, accessibility, and expense

Hypertension in adults: summary of updated NICE guidance

Home Blood Pressure Monitoring: Point-of-Care Testing

Feasibility of Telemonitoring Blood Pressure in Patients With Kidney Disease (Oxford Heart and Renal Protection Study-1): Observational Study. JMIR Cardio

Measurement of serum phosphate levels using a mobile sensor

Management of diabetes mellitus in patients with chronic kidney disease

Intensified blood glucose monitoring improves glycemic control in stable, insulin-treated veterans with type 2 diabetes: the Diabetes Outcomes in Veterans Study (DOVES)

Continuous glucose monitoring and intensive treatment of type 1 diabetes

Self-monitoring of blood glucose in type 2 diabetes and long-term outcome: an epidemiological cohort study

Effectiveness of continuous glucose monitoring in dialysis patients with diabetes: The DIALYDIAB pilot study

Continuous glucose monitoring in hemodialyzed patients with type 2 diabetes: A multicenter pilot study

Efficacy of self-monitoring of blood glucose versus retrospective continuous glucose monitoring in improving glycaemic control in diabetic kidney disease patients

Diabetes Technology in the Inpatient Setting for Management of Hyperglycemia

The Development of a Smart App for Patients with Type 2 Diabetes and Obesity. JMIR diabetes

Clinical pharmacology of oral anticoagulants in patients with kidney disease

Anticoagulation in Concomitant Chronic Kidney Disease and Atrial Fibrillation: JACC Review Topic of the Week

Anticoagulant strategies for the patient with chronic kidney disease

Patient self-testing is a reliable and acceptable alternative to laboratory INR monitoring

Improving the outcomes of anticoagulation: An evaluation of home follow-up of warfarin initiation

Effect of home testing of international normalized ratio on clinical events

Portable coagulometer for vitamin K-antagonist monitoring: The patients' point of view

Precision and accuracy of the new XPrecia Stride mobile coagulometer

An evaluation of a coagulation system (Xprecia Stride) for utilisation in anticoagulation management

Cochrane corner: Self-monitoring and selfmanagement of oral anticoagulation

Is self-monitoring an effective option for people receiving long-term vitamin K antagonist therapy? A systematic review and economic evaluation

Warfarin monitoring economic evaluation of point of care selfmonitoring compared to clinic settings

Point-of-care used in the treatment of older patients with cancer. The perception and experience of nurses

Approved for home use (Evidence supporting home use) Anaemia management Entia Luma Centrifugation and photometric detection with reagent free cuvette (Hb)Unpublished data, Entia 2020: Precision analysis using fixed control blood (103 repeats) at low (Hb 75g/L), normal (Hb 125g/L), high (Hb 175g/L) Hb values: CV 5.2%, 3.1%, 2.6% respectively. Paired capillary and venous blood samples (n=376) Luma vs. lab based Hb measurement (Beckman Coulter LH750) showed high correlation between devices (r=0.99, CV 7.1%). -StatSensor Xpress: Kosack 2015: n=60, acceptable to good utility in terms of repeatability, inter-device reproducibility and betweenrun reproducibility over time using quality control reagents; sufficient accuracy in detecting pathological samples based on the CV for repeatability and between-run reproducibility (2.3 to 5.9% and 4.2 to 9.0% respectively). Some under estimation of higher values was seen based on the Bland and Altman technique.

-StatSensor Creatinine: Van der Heijden 2019: n=120, exceeded predefined analytical error limits of 8.87% for creatinine and 10% for eGFR (creatinine: 15%, eGFR: 13%), with greater variation in results compared to i-STAT and epoc Blood Analysis System.