title: Pathophysiologic basis for normouricosuric uric acid nephrolithiasis.
abstract: BACKGROUND
  Low urinary pH is the commonest and by far the most important factor in uric acid nephrolithiasis but the reason(s) for this defect is (are) unknown. Patients with uric acid nephrolithaisis have normal acid-base parameters according conventional clinical tests.
  
  
  METHODS
  We studied steady-state plasma and urinary parameters of acid-base balance in subjects with normouricosuric pure uric acid stones. We also tested the ability of these subjects to excrete ammonium in response to an acute acid load. We compared these parameters in patients with pure uric acid stones to patients with mixed uric acid/calcium oxalate stones, pure calcium stones, and normal volunteers.
  
  
  RESULTS
  Pure uric acid stone formers have a much higher incidence of either diabetes or glucose intolerance. After equilibration to a control diet, patients with uric acid stones have lower urinary pH and they excrete less of their acid as ammonium. This is compensated by higher titratable acidity and hypocitraturia. Despite their low baseline urinary pH, uric acid stone formers further acidify their urine after an acid load because of a severely impaired ammonia excretory response. Their characteristics are significantly different from normal volunteers and pure calcium stone formers. Patients with mixed uric acid/calcium stones exhibit intermediate characteristics.
  
  
  CONCLUSIONS
  We propose that certain patients with normouricosuric uric acid nephrolithiasis have a renal acidification disease. The primary defect lies in renal ammonium excretion, which may be linked to the insulin-resistant state. Although net acid excretion is maintained at the expense of increased titratable acidity and to some degree hypocitraturia, the compromise is acid urine pH and may result in uric acid nephrolithiasis.
authors.affiliation: Center of Mineral Metabolism and Clinical Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8891, USA.
authors.forename: Khashayar
authors.initials: K
authors.lastname: Sakhaee
authors.forename: Beverley
authors.initials: B
authors.lastname: Adams-Huet
authors.forename: Orson W
authors.initials: OW
authors.lastname: Moe
authors.forename: Charles Y C
authors.initials: CY
authors.lastname: Pak
mesh_terms: D000328:Adult; D000368:Aged; D000643:Ammonium Chloride / Q000493:pharmacokinetics; D002129:Calcium Oxalate / Q000652:urine; D004232:Diuretics / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007669:Kidney Calculi / Q000209:etiology / Q000503:physiopathology* / Q000652:urine*; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood; D014527:Uric Acid / Q000652:urine*
chemical_list: D004232:Diuretics; D014280:Triglycerides; D000643:Ammonium Chloride; D002129:Calcium Oxalate; D014527:Uric Acid
keywords: Non-programmatic