Effects of dietary protein conditioning on gentamicin-induced nephrotoxicosis in healthy male dogs

Summary Eighteen 6-month-old male Beagles with normal renal function were allotted at random to 3 groups of 6 dogs each. For 21 days, each group was fed a diet that was similar except for protein content (high protein, 27.3%; medium protein, 13.7%; and low protein, 9.4%). After the conditioning period, gentamicin was administered at a dosage of 10 mg/kg of body weight, IM, every 8 hours for 8 days, and the respective diet was continued. Clearance of endogenous creatinine, 24-hour urinary excretion of protein and enzymes (γ-glutamyltransferase, and N-acetyl- β-d-glucosaminidase, and fractional clearance of sodium and potassium (%) were determined before and after dietary protein conditioning and on days 2, 4, 6, and 8 of gentamicin administration. Additionally, trough serum gentamicin concentration was determined on days 2, 4, 6, and 8 of gentamicin administration. At the end of the study, all dogs were euthanatized; renal histologic features were graded, using a continuous ranking scale, and renal cortical gentamicin concentrations were measured. Data were ranked and analyzed, using a nonparametric equivalent of a two-way anova; P < 0.05 was considered significant. After the dietary conditioning period (prior to gentamicin), dogs fed the high-protein diet had higher endogenous creatinine clearance and urinary excretion of protein, compared with dogs fed the low-protein diet. Differences existed among groups after 8 days of gentamicin administration. Dogs fed the high-protein diet had higher creatinine clearance, lower serum creatinine concentration, lower fractional clearance of sodium, lower urinary excretion of N-acetyl-β-d-glucosaminidase and lower trough serum gentamicin concentration, compared with dogs fed the medium- and low-protein diets. Dogs fed the high-protein diet also had lower urinary excretion of protein and lower fractional clearance of potassium, compared with dogs fed the low-protein diet. There was no difference in urinary excretion of γ-gluta-myltransferase among groups on day 8 of the study. Proximal tubular necrosis was more severe in dogs fed the medium-protein diet, compared with dogs fed the high-protein diet; however, there were no differences in renal cortical gentamicin concentrations among groups. In conclusion, feeding the high-protein diet prior to and during gentamicin administration reduced nephrotoxicosis in these dogs.