FINDING NEW INTERVENTIONS TO SLOW KIDNEY FUNCTION DECLINE IN DIABETES

Abstract

The focus of my research is on preventing kidney function loss in people with diabetes. Diabetic kidney disease (DKD) is a major cause of increased morbidity and mortality among persons with diabetes, and the estimated lifetime risk of DKD among patients with diabetes is as high as 60%. Many of the patients with DKD end up reaching end-stage-kidney disease (ESKD), requiring dialysis or kidney transplant to survive, which is a huge problem at the public health and personal levels. There are some current treatments to prevent DKD and GFR loss in diabetes. However, the two interventions that we have since the 1990s, inhibition of the renin-angiotensin system and intensive glycemic control, are only partially effective in preventing kidney function loss, and the same is true for novel interventions such as SGLT inhibitors and GLP-1 receptor agonists. Thus, there is a significant residual risk that must be addressed by finding novel interventions. To mitigate this lingering risk, my two thesis papers focus on the overarching objective of mitigating renal function deterioration in individuals with diabetes. The first paper is dedicated to designing more effective trials for DKD, with a specific emphasis on evaluating the efficacy of different enrollment strategies tailored to identify individuals with either albuminuric or normoalbuminuric DKD, who are predisposed to encountering renal function deterioration during the course of a trial. The second paper concerns improving cost-effectiveness of interventions to slow down the progression of kidney function decline in diabetic patients by personalizing treatment. It delves into the inquiry of whether biomarkers indicative of increased ESKD risk can reliably predict the response to ESKD-preventive therapies, such as fenofibrate, in individuals with diabetes.