ELEVATED SYSTEMIC LEVELS OF ANGIOTENSIN-(1-7) MODULATE RENAL DYSFUNCTION OBSERVERD IN THE EARLY PHASE OF DIABETIC KIDNEY DISEASE

The deleterious effects of hyperglycemia on glomerular and tubular cells are crucial in the development of Diabetic Kidney Disease (DKD). However, the mechanisms involved in this process are still elusive. In this present work, we aimed to study the potential modulatory effect of angiotensin-(1-7) [Ang-(1 7)], a component of the Renin-Angiotensin System, in DKD. We used 16-week old male L3292 transgenic rats, which present high systemic levels of Ang-(1 7), and Sprague Dawley (SD) rats as the respective controls. Type 1 diabetes mellitus was induced by a single injection of streptozotocin (STZ, 55 mg/kg). Four groups were generated: 1) SD-ND, normoglycemic SD rats (control, n=8); 2) SD-D, diabetic SD rats (n=8); 3) L3292-ND, normoglycemic L3292 rats (n=9); 4) L3292-D, diabetic L3292 rats (n=9) (CEUA-UFMG#100/2023). All analyses were performed after 3 weeks of diabetes. Diabetic groups presented similar levels of hyperglycemia (4.0-fold) as well as similar levels of increased glycosuria and urinary volumes (4.0-fold). Creatinine clearance (a marker of glomerular function) only increased (2.5-fold) in the L3292-D group. Regarding renal protein handling, despite a similar increase in proteinuria and renal clearance of proteins (3.0-fold and 2.81-fold, respectively) in both SD-D and L3292-D groups, the protein filtration was only increased (1.5-fold) in the L3292-D group. In addition, we observed a 1.35-fold increase in FEproteins associated with a 40% reduction in cortical albumin-FITC uptake in the SD-D group. Interestingly, these deleterious effects were not observed in the L3292 D group. Furthermore, a significant increase (8.4-fold) in urinary 𝛾-glutamyl transferase, a proximal tubule injury marker, was observed only in the SD-D group. Altogether, our preliminary data suggest that higher systemic levels of Ang-(1-7) promote dual effects on diabetic kidneys; it contributes to glomerular hyperfiltration while attenuating tubular dysfunction at early stages of DKD.