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.