Naim M Maalouf1, Mary Ann Cameron, Orson W Moe, Khashayar Sakhaee. 1. Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8885, USA.
Abstract
PURPOSE OF REVIEW: The factors involved in the pathogenesis of uric acid nephrolithiasis are well known. A low urinary pH is the most significant element in the generation of stones, with hyperuricosuria being a less common finding. The underlying mechanism(s) responsible for these disturbances remain poorly characterized. This review summarizes previous knowledge and highlights some recent developments in the pathophysiology of low urine pH and hyperuricosuria. RECENT FINDINGS: Epidemiological and metabolic studies have indicated an association between uric acid nephrolithiasis and insulin resistance. Some potential mechanisms include impaired ammoniagenesis caused by resistance to insulin action in the renal proximal tubule, or substrate competition by free fatty acids. The evaluation of a large Sicilian kindred recently revealed a putative genetic locus linked to uric acid stone disease. The identification of novel complementary DNA has provided an interesting insight into the renal handling of uric acid, including one genetic cause of renal uric acid wasting. SUMMARY: The recognition of metabolic, molecular, and genetic factors that influence urinary pH, and uric acid metabolism and excretion, will provide novel insights into the pathogenesis of uric acid stones, and open the way for new therapeutic strategies.
PURPOSE OF REVIEW: The factors involved in the pathogenesis of uric acidnephrolithiasis are well known. A low urinary pH is the most significant element in the generation of stones, with hyperuricosuria being a less common finding. The underlying mechanism(s) responsible for these disturbances remain poorly characterized. This review summarizes previous knowledge and highlights some recent developments in the pathophysiology of low urine pH and hyperuricosuria. RECENT FINDINGS: Epidemiological and metabolic studies have indicated an association between uric acidnephrolithiasis and insulin resistance. Some potential mechanisms include impaired ammoniagenesis caused by resistance to insulin action in the renal proximal tubule, or substrate competition by free fatty acids. The evaluation of a large Sicilian kindred recently revealed a putative genetic locus linked to uric acidstone disease. The identification of novel complementary DNA has provided an interesting insight into the renal handling of uric acid, including one genetic cause of renal uric acid wasting. SUMMARY: The recognition of metabolic, molecular, and genetic factors that influence urinary pH, and uric acid metabolism and excretion, will provide novel insights into the pathogenesis of uric acid stones, and open the way for new therapeutic strategies.
Authors: Nasser A Dhayat; Michael W Gradwell; Ganesh Pathare; Manuel Anderegg; Lisa Schneider; David Luethi; Cedric Mattmann; Orson W Moe; Bruno Vogt; Daniel G Fuster Journal: Clin J Am Soc Nephrol Date: 2017-08-03 Impact factor: 8.237
Authors: I Alexandru Bobulescu; Sun K Park; L H Richie Xu; Francisco Blanco; John Poindexter; Beverley Adams-Huet; Taylor L Davidson; Khashayar Sakhaee; Naim M Maalouf; Orson W Moe Journal: Clin J Am Soc Nephrol Date: 2019-02-11 Impact factor: 8.237