Pathophysiological and physicochemical basis of ammonium urate stone formation in dolphins.

ABSTRACT

PURPOSE: Nephrolithiasis is increasingly reported in bottle-nosed dolphins. All cases to date have been ammonium urate nephrolithiasis. MATERIALS AND METHODS: A case-control study was performed in dolphins with and without evidence of nephrolithiasis to identify biomarkers and risk factors associated with stone formation in a managed population. Dolphins were sampled in fasting and postprandial states to study the effect of dietary factors on serum and urinary biochemistry. Urine was continuously collected for 6 hours via catheter and divided into 3, 2-hour collections with a bolus fish meal given after completing the first collection. Blood was sampled at the beginning of the fasting period and the end of the postprandial period. RESULTS: There were no significant differences in serum and urine chemistry or acid-base profiles between dolphins with vs without stones at baseline or postprandially. This suggests that cases and controls represent a continuum of stone risk. On analysis combining cases and controls in a single cohort we noted significant postprandial increases in urinary uric acid, sulfate and net acid excretion accompanied by increased urinary ammonium excretion and a commensurate increase in urine pH. The supersaturation index of ammonium urate increased more than twofold postprandially. CONCLUSIONS: These findings suggest that dolphins are susceptible to ammonium urate nephrolithiasis at least in part because a high dietary load of acid and purines results in a transient but marked increase in the urinary supersaturation of the sparingly soluble ammonium urate salt.