Aerobic physical exercise modulates renal interlobar artery reactivity and tubular function in rats with early-stage DKD

Introduction: Diabetic Kidney Disease (DKD) is a microvascular complication of diabetes characterized by progressive loss of kidney function. However, aerobic exercise is an established adjunctive therapy for diabetes. Objective: To evaluate the effects of aerobic exercise on renal interlobar artery vascular reactivity and kidney function in rats with early-stage DKD. Materials and Methods: CEUA-UECE protocol: 31032.004642/2023-39. Male Wistar rats were divided into Control (CTL), Control + Exercise (CTL+EX), Diabetic (STZ), and Diabetic + Exercise (STZ+EX) groups. Diabetes was induced by a single intraperitoneal injection of streptozotocin (60 mg/kg). Exercised animals underwent an 8-week treadmill training protocol at 60% of maximal exercise capacity. The left renal interlobar artery was mounted on a wire myograph for concentration–response curves to potassium chloride (KCl), norepinephrine (NE), and sodium nitroprusside (SNP). Renal function was evaluated by creatinine clearance (eGFR), urinary protein profile (SDS-PAGE), renal handling of total protein, albumin and glucose, urinary γ-glutamyl transferase (γ-GT), lactate dehydrogenase (LDH), and immunoblotting for albumin, transferrin, and β2-microglobulin. Data were analyzed by one- or two-way ANOVA followed by Tukey's post hoc test (p < 0.05). Results: Aerobic exercise did not alter body weight, food and water intake, urine output, kidney weight, blood glucose, or renal glucose handling. Exercise capacity increased significantly in the STZ+EX (36%, p < 0.05) group compared to the sedentary groups (CTL and STZ). Vascular reactivity to KCl was reduced starting at 40 mM in STZ rats and improved by exercise. Diabetic rats (STZ group) showed increased sensitivity (EC50: 0.45 ± 0.100 µM) to NE but reduced maximal contraction, both of which were attenuated by exercise. Endothelium-independent relaxation to SNP was impaired in diabetic animals. STZ and STZ+EX groups exhibited increased eGFR (4.60 ± 0.6201 and 3.51 ± 0.3023 mL/min, respectively), with a trend toward normalization after exercise compared to controls (2.29 ± 0.2728 and 2.48 ± 0.4750). Exercise also significantly reduced (p < 0.05) proteinuria, improved renal albumin handling, and decreased γ-GT and LDH. Conclusion: Aerobic exercise improved the vascular reactivity of the renal interlobar artery and attenuated renal tubular dysfunction in the early stage of DKD.