| Outcome Measures: |
Primary: Effect of empagliflozin on change in cortical interstitial fractional volume [Vv(Int/cortex) over the 3-year study period., Cortical interstitial fractional volume is a measure of the proportion of kidney cortex made up of interstitium. The measurement is made using light microscopy images of kidney tissue. It is positively associated with progression of diabetic kidney disease and is the glomerular measurement that changes most dramatically over time in diabetic kidney disease. We will compare change in cortical interstitial fractional volume from baseline to 3-year biopsy in the group randomized to Empagliflozin and the group randomized to placebo., 3 years | Secondary: Effect of empagliflozin on changes in total interstitium per cortex per kidney, mesangial fractional volume, glomerular basement membrane width, glomerular filtration surface density, and total filtration surface per glomerulus., Changes in total interstitial volume (calculated from the cortical interstitial fractional volume and cortical volume assessed by MRI) along with key glomerular morphometric measurements (mesangial fractional volume, glomerular basement membrane width, glomerular filtration surface density, and total filtration surface per glomerulus) assessed using electron microscopy images, are all associated with progression of diabetic kidney disease. We will compare change in total cortical interstitial volume and other glomerular measures from baseline to 3-year biopsy in the group randomized to Empagliflozin and the group randomized to placebo., 3 years|Effect of empagliflozin on changes in podocyte numerical density, podocyte number per glomerulus, podocyte foot process width, percentage podocyte detachment, and percentage glomerular endothelial cell fenestration., As diabetic kidney disease progresses podocytes are lost, and the barrier made up of podocyte foot processes and endothelial cell fenestrations becomes more porous. We will compare change in these podocyte measures from baseline to 3-year biopsy in the group randomized to Empagliflozin and the group randomized to placebo., 3 years|Effect of empagliflozin on development or progression of diabetic retinopathy determined by changes from baseline to 3 years of at least 2 Early Treatment of Diabetic Retinopathy Study levels in grading of standardized retinal photographs., Diabetic retinopathy is another microvascular complication of diabetes and untreated can lead to loss of sight. Diabetic retinopathy is detected and staged using digital retinal photography. We will test for effects of Empagliflozin treatment on the incidence of new retinopathy and the progression of existing retinopathy from baseline to 3- years in the group randomized to Empagliflozin and the group randomized to placebo., 3 years
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