Heat and humidity stress aggravate high-fat diet-induced kidney damage in albino rats.

High-fat diet and environmental stressors such as heat and humidity are known to impair physiological functions. This study investigates the combined effects of HFD and stress based on the temperature–humidity index on kidney function in male and female rats. A total of 90 male and 90 female rats were divided into six groups with routine diet (RD) and high-fat diet (HFD): controls (G1-RD, G2-HFD), heat-stressed (G3-RD, G4-HFD), and humidity-stressed (G5-RD, G6-HFD). Stress groups were exposed to 4 h/day of heat or humidity for 30 days. Serum biomarkers urea, creatinine, uric acid, and BUN were measured at three decapitation intervals (Days 10, 20, and 30). Kidney tissues were processed for histological evaluation. HFD-fed rats showed markedly higher urea, uric acid, and BUN levels compared to RD-fed rats, with males exhibiting greater elevations than females (P < 0.05). Heat and humidity stress further intensified these biochemical changes, particularly in HFD-fed groups, with the highest values observed at the 3rd decapitation. Creatinine levels rose progressively over-time regardless of stress but were diet-dependent. Histological findings revealed normal renal architecture in RD controls, mild vascular congestion in HFD controls, and pronounced renal injury, including glomerular shrinkage, tubular epithelial degeneration, cortical congestion, and epithelial desquamation in stressed HFD groups. Humidity stress produced slightly more severe damage than heat stress. Heat and humidity stress aggravate HFD-induced kidney damage, highlighting the need for dietary fat control and reduced heat exposure to protect renal health.