EFFECTS OF DIETARY-PROTEIN CONDITIONING ON GENTAMICIN-INDUCED NEPHROTOXICOSIS IN HEALTHY MALE DOGS

Eighteen 6-month-old male Beagles with normal renal function were allo tted 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 condi tioning 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 wa s continued. Clearance of endogenous creatinine, 24-hour urinary excre tion of protein and enzymes (gamma-glutamyltransferase, and N-acetyl-b eta-D-glucosaminidase, and fractional clearance of sodium and potassiu m (%) were determined before and after dietary protein conditioning an d on days 2, 4, 6, and 8 of gentamicin administration. Additionally, t rough serum gentamicin concentration was determined on days 2, 4, 6, a nd 8 of gentamicin administration. At the end of the study, all dogs w ere euthanatized; renal histologic features were graded, using a conti nuous ranking scale, and renal cortical gentamicin concentrations were measured. Data were ranked and analyzed, using a nonparametric equiva lent of a two-way ANOVA; P < 0.05 was considered significant. After th e dietary conditioning period (prior to gentamicin), dogs fed the high -protein diet had higher endogenous creatinine clearance and urinary e xcretion of protein, compared with dogs fed the low-protein diet. Diff erences existed among groups after 8 days of gentamicin administration . Dogs fed the high-protein diet had higher creatinine clearance, lowe r serum creatinine concentration, lower fractional clearance of sodium , lower urinary excretion of N-acetyl-beta-D-glucosaminidase and lower trough serum gentamicin concentration, compared with dogs fed the med ium- and low-protein diets. Dogs fed the high-protein diet also had lo wer urinary excretion of protein and lower fractional clearance of pot assium, compared with dogs fed the low-protein diet. There was no diff erence in urinary excretion of gamma-glutamyl-transferase among groups on day 8 of the study. Proximal tubular necrosis was more severe in d ogs fed the medium-protein diet, compared with dogs fed the high-prote in diet; however, there were no differences in renal cortical gentamic in concentrations among groups. In conclusion, feeding the high-protei n diet prior to and during gentamicin administration reduced nephrotox icosis in these dogs.