Abstract
Nephrolithiasis has been reported in bottlenose dolphins, and most of these nephroliths have been composed of 100% ammonium acid urate (AAU).1,2 We are investigating therapies to treat and prevent nephrolithiasis in dolphins, including the alkalization of urine for dissolution of nephroliths. Little data exist regarding the optimal pH required for complete dissolution of AAU nephroliths. This study checks the solubility of AAU nephroliths in a phosphate buffer, pH range 6.0–8.0, and in a carbonate/bicarbonate buffer, pH range 9.0–10.8. Six nephrolith samples, which were confirmed ammonium acid urate stones, were obtained from the Navy Marine Mammal Program. The samples were triturated and dissolved at 1mg/mL concentration in the sets of buffers, prepared in 0.2 pH unit increments. Samples were vortexed for 1 hr, and the solubility of nephroliths was measured by C18 RP-HPLC with UV detection at 290 nm using Dionex Ultimate 3000 workstation. Among all six nephroliths, there was no significant change in the solubility over the pH range 6.0–8.0. The solubility increased linearly in the pH range 9.0–10.2, then remained the same in the pH range 10.2–10.8. One observation in the pH range 6.0–8.0 was that the nephrolith solubility was 42% lower in potassium phosphate buffer compared to sodium phosphate buffer, indicating these nephroliths have a much higher solubility in sodium phosphate buffer. These results may explain why currently available oral therapies using alkalinizing agents such as potassium citrate would be ineffective and indicate that much higher pH is needed for complete dissolution of the nephroliths in dolphins.
References
1. Venn-Watson S, Smith CR, Daniels R, Townsend F. Clinical relevance of urate nephrolithiasis in bottlenose dolphins (Tursiops truncatus). Dis Aqua Org 2010; 89: 167–177.
2. Venn-Watson S, Townsend FI, Daniels R, Sweeney J, McBain J, Klatsky L, Hicks C, Staggs L, Rowles T, Schwacke L, Wells RS, Smith CR. Hypocitraturia in Atlantic bottlenose dolphins (Tursiops truncatus): Assessing a potential risk factor for urate nephrolithiasis. Comp Med 2010; 60: 149–153.