Source-Dependent Renal Effects of Commercial Protein Supplements: A 28-Day Study in Rats

Background and Objectives: Commercial protein powders are widely consumed to increase dietary protein intake, yet whether their renal effects differ by protein source remains poorly characterized. The primary objective of this study was therefore to determine whether 28 days of administration of commercial whey, casein, soy or beef protein powder produces source-dependent renal histopathological injury in rats, with the total renal injury score as the primary outcome. Secondary objectives were to assess conventional renal function markers and the renal oxidative stress response. Materials and Methods: Thirty-five female Sprague Dawley rats were stratified by body weight and randomly assigned to five groups (n = 7 per group): control, whey, casein, soy and beef. The powders were given by oral gavage in 0.9% sterile isotonic saline at 400 mg/kg/day of protein for 28 consecutive days; controls received the vehicle only. Body weight, kidney-to-body weight ratio, serum urea and creatinine, urinalysis, renal histopathology, renal oxidative stress parameters and the elemental composition of the powders were assessed. Results: Protein supplementation did not significantly affect body weight, kidney-to-body weight ratio, serum urea, creatinine or urinalysis findings in any group. Despite this, renal responses differed by protein source. All powders produced mild-to-moderate tubular change relative to the control. The beef group showed the highest total injury score and was the only group that differed from control in every parameter, although the protein groups did not differ from one another. The oxidative response also differed by source: renal malondialdehyde (MDA) was highest in the beef group and significantly exceeded the casein and soy groups, whereas catalase (CAT) activity was significantly reduced in the whey and casein groups. Glutathione peroxidase (GSH-Px) and nitrite levels were unchanged. Estimated metal exposure from all powders remained below toxicological risk thresholds. Conclusions: The renal effects of commercial protein powders are source-dependent even at a low dose and in the absence of any change in conventional renal function markers. Beef protein was associated with the highest lipid peroxidation and casein with the largest fall in enzymatic antioxidant capacity, two distinct oxidative signatures. These effects, and their progression under longer-term exposure, warrant further investigation.