Novel insights into the pathogenesis of uric acid nephrolithiasis.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Maalouf
Naim M
NM
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.
Cameron
Mary Ann
MA
Moe
Orson W
OW
Sakhaee
Khashayar
K
D002940:Circadian Rhythm; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007333:Insulin Resistance / Q000502:physiology; D007674:Kidney Diseases / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D020347:Lithiasis / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D012307:Risk Factors; D014527:Uric Acid / Q000378:metabolism / Q000652:urine*
D005973:Glutamine; D014527:Uric Acid