Effects of a prostaglandin E1 analogue, misoprostol, on renal function in dogs receiving nephrotoxic doses of gentamicin

OBJECTIVE: To determine whether the prostaglandin E1 analogue, misoprostol, could preserve renal function in dogs receiving nephrotoxic doses of gentamicin. ANIMALS: 12 (6/group) healthy sexually intact male dogs. PROCEDURE: All dogs were given high doses of gentamicin (10 mg/kg of body weight, i.v., q 8 h, for 8 consecutive days). Six dogs (treatment group) received misoprostol (3 microgram/kg, p.o., q 8 h for the duration of the study) and 6 dogs (control group) received vehicle (1 capsule, p.o., q 8 h). Renal function was assessed before treatment (day 0) and on days 3, 6, 9, and 11 after initiation of treatment by measurement of serum biochemical variables, urine specific gravity, and exogenous creatinine clearance. Serum electrolyte and protein concentrations and presence of proteinuria, glycosuria, and cylindruria were also determined. At the end of the study, renal histopathologic changed were evaluated. RESULTS: Dogs receiving misoprostol had significant reduction in exogenous creatinine clearance with time, compared with dogs receiving vehicle (P = 0.0264). Dogs receiving misoprostol tended to develop more severe azotemia, hyperphosphatemia, and renal histopathologic changes; however, results were not significantly different between groups. CONCLUSION: Misoprostol (3 microgram/kg, p.o., q 8 h) did not preserve renal function and may have exacerbated gentamicin-induced nephrotoxicosis in this group of dogs. CLINICAL RELEVANCE: Supplementation of vasodilatory prostanoids may exacerbate renal dysfunction in dogs receiving high doses of gentamicin.