Uric acid nephrolithiasis: proton titration of an essential molecule?
OBJECTIVE
The majority of uric acid nephrolithiasis in humans occurs in the absence of frank hyperuricosuria and is primarily a disease of excessively low urinary pH. Uric acid is substantially less soluble than urate salts so in low urine pH urate is protonated, thus favoring precipitation even under what is considered physiologic concentrations of total urinary uric acid/urate. This commentary examines the rationales behind the existence of uric acid in urine and body fluids in vertebrate evolution.


RESULTS
The purpose of uric acid in arthropod, avian and reptilian species is to enable nitrogen excretion in solid state without loss of water. The re-emergence of uric acid in higher primates as an end product of metabolism is intriguing since urea functions perfectly well as a nitrogenous waste. Uric acid must purvey important physiologic functions in primate biology. Numerous roles of uric acid as an antioxidant, immune signaling molecule, and a defender of circulatory integrity have recently been proposed.


CONCLUSIONS
There is little doubt that uric acid serves multiple important functions in higher primates. It is also conceivable, however, that this important molecule when present in the wrong concentration or context can lead to undesirable phenotypes.
Moe
Orson W
OW
Charles and Jane Pak Center of Mineral Metabolism and Clinical Research and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8855, USA. Orson.Moe@UTSouthwestern.edu
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D005075:Biological Evolution; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053040:Nephrolithiasis / Q000276:immunology / Q000652:urine; D010641:Phenotype; D015398:Signal Transduction / Q000276:immunology; D013045:Species Specificity; D014508:Urea / Q000276:immunology / Q000378:metabolism; D014527:Uric Acid / Q000276:immunology / Q000378:metabolism*
D000975:Antioxidants; D014527:Uric Acid; D014508:Urea