Application of a Nanotechnology-Based, Point-of-Care Diagnostic Device in Diabetic Kidney Disease

Abstract

IntroductionEarly detection of diabetes mellitus (DM) and diabetic kidney disease (DKD) is important for preventing end-stage renal failure and reducing cardiovascular complications. Availability of a validated point-of-care (PoC) device that can measure various DKD markers would be useful in this respect, especially in resource-poor parts of the world.MethodsWe validated a novel nanotechnology-based multianalyte PoC device (minimally invasive and does not require trained medical personnel) against laboratory gold standard tests for the detection of 5 biomarkers related to management of DM and DKD. The prospective study was funded by an International Society of Nephrology American Nephrologists of Indian Origin grant in 2 phases: (i) proof of concept: random samples were tested for the analytes with the PoC device and correlated with the laboratory gold standard; and (ii) clinical validation in a well-characterized cohort of patients. A nonenzymatic- and nonantibody-based electrochemical PoC device for quantitative measurement of markers—glycosylated hemoglobin (HbA1c), hemoglobin, serum albumin, microalbuminuria, urine creatinine, and albumin-to-creatinine ratio−was developed and used in this study. The disposable strips were interfaced with a multipotentiostat hand-held PoC device (3.7-V rechargeable lithium battery, 5-inch touch screen, Bluetooth enabled) working in amperometry mode, which provided the results in <1 minute. Data were analyzed using linearity plots and Bland-Altman difference plot analysis.ResultsA total of 4717 individuals were screened during the study (phase 1: 2576 and phase 2: 2141.) In phase 2, samples were tested in 529 subjects (346 females)—120 subjects with type 1 DM, 255 subjects with type 2 DM, 54 subjects without DM, 400 subjects with stage 2 chronic kidney disease, and 30 subjects with stage 3 chronic kidney disease.ConclusionA nanotechnology-based PoC device for quantitative measurement of HbA1c, hemoglobin, serum albumin, microalbuminuria, and the urine albumin-to-creatinine ratio was developed for detection of early DKD and showed excellent correlation between the device and laboratory results. This device has the potential for early detection of DM and/or DKD, especially in remote communities in underserved areas of the world where prevalence of diabetes is rapidly increasing.

Current Trends of Nanobiosensors for Point-of-Care Diagnostics

“…Diabetes is a fast developing problem currently affecting millions of people worldwide [39]. It can lead to several serious complications such as lower limb amputations, blindness, cardiovascular diseases [39], and diabetic kidney disease [40]. Though diabetes has no cure, patients can reduce its complications by tightly monitoring and controlling the blood glucose levels [7, 39, 41].…”

“…Though diabetes has no cure, patients can reduce its complications by tightly monitoring and controlling the blood glucose levels [7, 39, 41]. Early detection and strategies to prevent the progression of diabetes would make a big difference for the patients and would also be economically beneficial for a resource-constrained country [40]. Studies have shown that the control of blood glucose level in the normal range, commonly found in the range of 4.9–6.9 mM in healthy individuals, can help amelioration of microvascular (nephropathy, neuropathy, and retinopathy) and macrovascular (coronary artery disease and stroke) complications [7].…”

“…For example, the sampling process is painful and analysis cannot be done if patient is not awake and missing large fluctuations between sampling time points [39, 42–44]. Also, early diagnostic in remote and resource-constrained setting is challenging with no access to expensive well-equipped clinical laboratories and trained medical personnel [40]. Because of these limitations in diagnostic methods, substantial research efforts are focusing on developing enhanced methods to measure blood glucose levels.…”

Newer Point-of-Care Biosensors Are Expected to Permit Early Detection and Better Management of Acute and CKD

“…In this issue of Kidney International Reports , Kumar et al. 9 reported on the clinical application of a nanotechnology-based multianalyte POC biosensor diagnostic device in Bangalore, India. The device was minimally invasive, could be used with minimal training, and was able to measure many of the critical variables important in the detection and management of diabetic kidney disease (glycosylated hemoglobin, hemoglobin, serum and urine albumin, urine creatinine, and the albumin-to-creatinine ratio).…”

“…A large proof-of-concept and an even larger validation cohort make for reliable measurement results compared with gold standard laboratory results, as shown by the high correlation coefficients (R 2 > 0.8) and good linearity. It is expected that the use of devices (such as this POC device) in remote communities in underserved areas of the world, where the incidence and prevalence of diabetes mellitus and diabetic kidney disease continues to increase exponentially 9 and where delivery of care is woefully inadequate, will result in significant improvement in recognition and early management of diabetes and its complications. Deployment of inexpensive, simple devices such as this will exponentially increase the visibility of these problems and hopefully lead to implementation of measurable interventions that will affect the length and quality of millions of lives.…”