Primary Objective:To study podocyte specific injury markers in African American Veterans with non-diabetic kidney disease(NDKD), on empagliflozin therapy.

Primary Endpoint: Assess the effect of Empagliflozin on podocyte-specific proteins in exosomes isolated from subjects' urine, such as nephrin, podocalyxin and Wilms'Tumor (WT-1) protein.

Secondary Objective:

1. Correlate changes in exosome-based podocyte specific proteins with standardized biomarkers of kidney injury including urine albumin/creatinine ratio (ACR) and estimated GFR.
2. Correlate systemic inflammatory markers (focusing on vascular and endothelial function) that are already established such as interleukins (IL1, IL6, IL-12) , hs-CRP and arterial stiffness measures with urine exosome-based podocyte protein estimation.
3. Correlate urine podocyte-specific protein markers with APOL1 mRNA expression levels in blood mononuclear cells (MNC)

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.

Inclusion Criteria:

1. African American veterans
2. Age > 18 years
3. eGFR ≥20-59 mL/min/1.73 m2 by the CKD-EPI equation, with or without any degree of albuminuria OR
4. eGFR 60-89, with UACR of ≥30mg/g
5. BMI = 18-39.9
6. Blood pressure controlled to ≤140/90
7. Subjects without diabetes: will be screened using routine glucose level test: of less than 126 fasting glucose or less than 200mg/dl of random or post glucose blood glucose level in standard of care laboratory workup.
8. Ability to provide informed consent before any trial related activities are conducted.

Exclusion Criteria:

1. Diagnosed with Type 1 or Type 2 Diabetes Mellitus
2. Any prescribed diabetes medication for patients, such as GLP1RA, SGLT2is, and sulphonylureas
3. If a patient is on statin, need to be on a stable dose for a month.
4. Biopsy proven diagnosis of glomerular disease/glomerulonephritis
5. Active smokers,
6. Active skin wounds undergoing treatment or recent surgery within 1 month (due to possible aberrations in glycemic control)
7. Women who are pregnant, planning to become pregnant, nursing mothers, women of childbearing potential not using birth control measure
8. Hypersensitivity to empagliflozin or any of the excipients in Jardiance, reactions such as angioedema
9. Patients on dialysis
10. eGFR less than 20 mL/min/1.73 m2 by the CKD-EPI equation
11. Planned surgery or planned hospital admission within 5 months of participation in the study
12. At the discretion of PI to ensure health, safety, and well-being of the veteran, participation in this study may be stopped (please see withdrawal criteria)
13. Patients with prior history of diagnosis of heart failure with documented EF of less than 50.
14. Proven diagnosis of Polycystic Kidney Disease.