AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Effects of Moderate Physical Training on Renal Hemodynamics, Oxidative Stress, Inflammation, and Tubular Injury in Experimental Tenofovir Nephrotoxicity
By veloso gusmao silva J, Garcia Villalba J, Oliveira Silva E et al.
Introduction: Tenofovir Disoproxil Fumarate (TDF) nephrotoxicity is associated with tubular injury, oxidative stress, inflammation, and renal hemodynamic dysfunction. Whether exercise training protects against TDF-induced kidney injury remains unclear. We investigated the effects of moderate physical training on renal function, oxidative stress, inflammation, and renal hemodynamics in experimental TDF nephrotoxicity. Methods: Male Wistar rats were assigned to Control, TDF, Physical Training (PT), or TDF+PT groups (n=7/group). TDF-treated animals received 600 mg/kg/day by gavage for 5 days. PT consisted of swimming exercise (60 min/day, 5 days/week, 5% body weight overload) for 28 days. Renal function was evaluated by serum creatinine, inulin clearance, and urinary neutrophil gelatinase-associated lipocalin (NGAL). Renal hemodynamics included mean arterial pressure (MAP), renal blood flow (RBF), and renal vascular resistance (RVR). Oxidative stress was assessed by urinary peroxides (FOX), TBARS, thiols, and catalase activity. Renal inflammation was evaluated by CD68 immunostaining. Results: TDF induced significant renal dysfunction, evidenced by increased serum creatinine (0.93±0.10 vs. 0.30±0.10 mg/dL), elevated urinary NGAL (10.0±2.2 vs. 4.8±0.3 ng/mL), and reduced inulin clearance (0.29±0.10 vs. 1.14±0.10 mL/min; p<0.0001). These changes were accompanied by increased MAP (128±3 vs. 100±2 mmHg), reduced RBF (3.5±0.3 vs. 6.9±0.3 mL/min), increased RVR (36.3±3.1 vs. 14.4±0.6 mmHg/mL/min), marked oxidative stress, and increased macrophage infiltration. Physical training significantly attenuated renal injury, preserving inulin clearance (1.21±0.20 mL/min), reducing urinary NGAL (6.6±1.7 ng/mL), improving RBF (6.1±0.6 mL/min), and reducing RVR (18.0±2.0 mmHg/mL/min) (all p<0.0001 vs. TDF). Exercise also reduced oxidative damage, restored antioxidant defenses, and attenuated tubulointerstitial fibrosis. Conclusions: Moderate physical training protected against TDF-induced kidney injury through preservation of renal hemodynamics, reduction of oxidative stress, and attenuation of inflammatory responses. These findings support exercise training as a potential non-pharmacological strategy to mitigate TDF-associated nephrotoxicity.