Idiopathic uric acid nephrolithiasis is characterized by elevated urinary net 
acid excretion and insufficient buffering by ammonium, resulting in excessively 
acidic urine and titration of the relatively soluble urate anion to insoluble 
uric acid. Patients with type 2 diabetes have similar changes in urinary pH, net 
acid excretion, and ammonium in 24-h urine collections at baseline, even after 
controlling for dietary factors, and are at increased risk for uric acid 
nephrolithiasis. However, not all patients with type 2 diabetes develop kidney 
stones, suggesting that uric acid stone formers may have additional urinary 
defects, perhaps not apparent at baseline. We performed a metabolic study of 14 
patients with idiopathic uric acid nephrolithiasis, 13 patients with type 2 
diabetes, and 8 healthy control subjects of similar body mass index. After 
equilibration on a fixed diet for 5 days, subjects were given a single oral acid 
load (50 meq ammonium chloride), and urine was collected hourly for 4 h. Uric 
acid stone formers had a lower ammonium excretory response to acute acid loading 
compared with diabetic and nondiabetic nonstone formers, suggesting that an 
ammonium excretory defect unique to uric acid stone formers was unmasked by the 
acid challenge. The Zucker diabetic fatty rat also did not show impaired urinary 
ammonium excretion in response to acute acid challenge. A blunted renal ammonium 
excretory response to dietary acid loads may contribute to the pathogenesis of 
idiopathic uric acid nephrolithiasis.