Studies on the pathophysiology of the low urine pH in patients with uric acid stones

Background. A very low urine pH is the major risk factor for uric acid stone formation. Methods. A subgroup of patients with a history of uric acid stones and a persistently low urine pH (<5.5 for at least 12 h/day) were selected for detailed study. Based on their relative ammonium (NH4+) and sulfate (SO42-) excretions, patients were divided into two groups. Results. The first g roup (N = 2) excreted 173 and 139% more NH4+ than SO42-. Their daily urinary unmeasured anion excretion was higher than their calculated net diet alkali input (38 and 61 vs. 24 and 49 mEq, respectively). In the second group (N = 12), NH4+ excretion was 69 +/- 5% that of SO42-. In 2 of 12, decreased renal ammoniagenesis was suspected due to a plasma potassium of 5.3 mmol/L and/or a lower GFR (65 and 59 L/day); these patients had an extremely low citrate excretion (3 and 1 mEq/day). In contrast, citrate excretion was not low in the remaining 10 patients (10.4 +/- 1.3 mEq/day). Conclusions. Patients in group I needed a higher NH4+ excretion possibly because of a H+ load from excessive renal excretion of organic anions. We speculate that all alkaline proximal tubular cell pH could be the basis for the low NH4+ and high citrate excretions in 10 of 12 patients in group 2. Dietary factors and/or a molecular lesion may contribute to their pathophysiology.