Effect of Empagliflozin on Podocyte Specific Proteins in African American Veterans With NDKD

Nephropathy is a progressive complication of DKD and NDKD and substantially increases morbidity and mortality. Clinicians frequently measure proteinuria using urine protein /creatinine and urine albumin/creatinine ratios, which in several instances do not manifest substantial improvement, even after an intervention such as SGLT2i, particularly if the intervention period is is less than 6 months. There is therefore a clear need for other markers of podocyte injury in early phases of chronic kidney disease. Based on published studies, podocyte-specific injury proteins such as podocalyxin, Nephrin and Wilms tumor 1 (WT1) can be candidate marker proteins of injury. Urinary exosome analysis is a non-invasive and potentially more sensitive assay. These sensitive markers would reduce the need for biopsies to detect podocytopathy. The Veterans Health Administration has been a prominent caregiver to the African American community across the United States. Over the past decade, investigators have established the basic population genetics and epidemiology of APOL1-associated kidney disease and are making progress in understanding disease mechanisms at the cellular and molecular levels. With therapeutic approaches for APOL1 kidney disease now being explored by many groups in pharma and academia, studies to assess the relationship of APOL1 gene expression levels with podocyte injury in CKD are of paramount importance and will better inform treatment in the near future. These studies may address one important cause of the significant racial disparity in CKD rates among African-Americans. This study aim to explore mechanistic insights gained from the effect of SGLT2i on podocyte injury markers further in the backdrop of APOL1 expression, to understand the potential therapeutic impact SGLT2i may have in this clinical context. As APOL-1 gene mutation is much more common in African Americans and approximately 80% of VA population is African Americans, this study has been decided to enroll only from African American race in order to keep the population homogenous and achieve statistically significant results. Though the study will only include African Americans the study will be quite relevant in USA as worsening CKD is a major health problem in this country and the African American patient population is at particularly at a high risk for progressive CKD. A largely under-recognized public health issue, CKD is the ninth leading cause of death in the U.S. today. Although African Americans constitute 13% of the population, they suffer more than triple the rate of kidney failure of Caucasians.