Masterclasses in medicine Recurrent uric acid stones

A 46-year-old female had a history of recurrent uric acid stone formation, but the reason why uric acid precipitated in her urine was not obvious, because the rate of urate excretion was not high, urine volume was not low, and the pH in her 24-h urine was not low enough. In his discussion of the case, Professor McCance provided new insights into the pathophysiology of uric acid stone formation. He illustrated that measuring the pH in a 24-h urine might obscure the fact that the urine pH was low enough to cause uric acid to precipitate during most of the day. Because he found a low rate of excretion of NH4 + relative to that of sulphate anions, as well as a high rate of citrate excretion, he speculated that the low urine pH would be due to a more alkaline pH in proximal convoluted tubule cells. He went on to suspect that there was a problem in our understanding of the function of renal medullary NH3 shunt pathway, and he suggested that its major function might be to ensure a urine pH close to 6.0 throughout the day, to minimize the likelihood of forming uric acid kidney stones.