Noninvasive Biomarker Detection of Early Kidney Disease in Patients with Insulin Resistance

PROJECT SUMMARY There are over 420 million people living with type 2 diabetes mellitus (T2DM) in the world today and about 165 million also have chronic kidney disease (CKD). The prevalence of CKD is up to 5-fold higher in those with T2DM – in fact, andgt;50% of all T2DM patients will develop CKD in their lifetime. The presence of comorbid CKD in diabetes shortens average life expectancy by ~16-years, and results in ~$250 billion/yr in healthcare costs. Annual mortality rates, manifestation of life-impairing comorbidities like cardiovascular disease, and overall healthcare spending are all greatly increased as CKD severity progresses in T2DM. There is a significant unmet clinical need to identify CKD early in the course of diabetes. Impact of early diagnosis (and proactive implementation of CKD management) in the beginning stages of insulin resistance has been recognized by multiple international societies, yet, no early diagnostic test exists. Prediabetes, the precursor condition to T2DM, currently affects an estimated 88 million U.S. adults, and nearly 90% are unaware of their condition, suggesting that many of these patients are uninhibitedly progressing. While therapeutic intervention is known, proactive medical treatment for every prediabetic patient is impractical since most are low-risk for acutely developing T2DM or kidney disease. Recent findings suggest that a hitherto unclassified pathophysiological process results in rapid progression of prediabetes to T2DM, as well as early development of late-stage CKD. Yet, there is currently no mechanism in place to predict or stratify this “high-risk” subpopulation within prediabetes (that would benefit from early implementation of targeted medical therapy). AMDX PROGNOSTX will produce a new ELISA test that indicates the presence of an ongoing, subclinical pathological process that accelerates T2DM-associated comorbidities and rapid development of irreversible CKD in those with insulin resistance as early as the prediabetic stage. Our test is based on the use of a novel biomarker that reflects critical events in the pathophysiology of CKD progression within this specific prediabetic/early T2DM population. Preliminary results demonstrate that patients with elevated levels of this biomarker either already have, or rapidly develop CKD, and have a particularly high mortality rate. In this Phase I proposal, we will further develop and test our prototype mAb-based assay on longitudinal human samples to evaluate its ability to discern between two populations: i) prediabetic patients who readily developed CKD and T2DM after the onset of their diagnosis, and ii) prediabetic patients who never develop any form of CKD and/or T2DM. Results of this test will offer physicians a new dimension of insight that will redefine the field of diabetes and CKD management and offer advancements in the clinical decision-making process by prompting early medical treatment that will slow, and possibly prevent, progression to late-stage CKD. We request Phase I support to test feasibility of our project and optimize a test that will aid physicians in identifying these high-risk patients in the earliest stages of CKD. Ultimately, we intend to obtain FDA-approval and CMS coverage/reimbursement.PROJECT NARRATIVEKidney disease is a common condition within the diabetic community with an increasing prevalence that is associated with significant morbidity and mortality and is responsible for a large financial burden on the U.S. healthcare system. There is a substantial unmet clinical need to identify patients early in the course of insulin resistance – who are at a particularly high-risk for rapidly developing type 2 diabetes (T2DM) and late-stage chronic kidney disease (CKD) – with a non-invasive, accurate, sensitive, and objective measure that stratifies the prediabetic patient population and promotes early preventative treatments before irreversible, life-impairing kidney damage incurs. To help address this recognized public health crisis, AMDX PROGNOSTX is requesting support to develop our “RBCAmy-CKD Assay” to prove feasibility and determine accuracy for early identification of subclinical CKD in prediabetic and early-stage T2DM patients.