Uric acid stone disease: Lessons from recent human physiologic studies

Triet Vincent M. Tran, Naim M. Maalouf

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations


Purpose of reviewAn overly acidic urine resulting in supersaturation of urine with respect to uric acid is the major mechanism responsible for uric acid nephrolithiasis. The present review summarizes findings from recent human physiologic studies examining the pathophysiology and reversibility of low urine pH in uric acid stone formers.Recent findingsEpidemiologic and metabolic studies have confirmed an increase in the prevalence of uric acid nephrolithiasis and reported its association with several features of the metabolic syndrome including dyslipidemia, hyperglycemia, hepatic steatosis, and greater visceral adiposity. Physiologic studies in uric acid stone formers have identified diet-independent excessive net acid excretion and concomitant reduction in urinary buffering from impaired renal ammoniagenesis as the two causes underlying the greater aciduria. Administration of the insulin sensitizer pioglitazone to uric acid stone formers reduced the acid load presented to the kidney and enhanced ammoniagenesis and ammonium excretion, resulting in significantly higher urine pH.SummaryRecent human physiologic studies have identified greater acid excretion and reduced urinary buffering by ammonia as two culprits of aciduria in uric acid nephrolithiasis that can be reversed by pioglitazone, raising new questions regarding the origin of the aciduria and opening the door to pathophysiology-based treatment of uric acid stones.

Original languageEnglish (US)
Pages (from-to)407-413
Number of pages7
JournalCurrent opinion in nephrology and hypertension
Issue number4
StatePublished - Jul 1 2020


  • metabolic syndrome
  • nephrolithiasis
  • net acid excretion
  • uric acid
  • urine pH

ASJC Scopus subject areas

  • Internal Medicine
  • Nephrology


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