Uric Acid and Urate in Urolithiasis: The Innocent Bystander, Instigator, and Perpetrator

Uric acid is an end product of purine metabolism in human beings. An unusual and still unexplained phenomenon is that higher primates have relatively high uric acid levels in body fluids owing to a combination of absence of degradation and renal retention. The physiologic purpose of high uric acid levels still is enigmatic, but the pathobiologic burden is a variety of crystallopathies owing to the low aqueous solubility of uric acid such as gouty arthritis and acute uric acid nephropathy. In the urinary space, three distinct conditions result from chronic uric acid and/or urate precipitation. The first and most common variety is uric acid urolithiasis. In this condition, urate is a victim of a systemic metabolic disease in which increased acid load to the kidney is coupled with diminished urinary buffer capacity owing to defective ammonium excretion, resulting in titration of urate to its sparingly soluble protonated counterpart, uric acid, and the formation of stones. Uric acid is the innocent bystander of the crime. The second variety is hyperuricosuric calcium urolithiasis, in which uric acid confers lithogenicity via promotion of calcium oxalate precipitation by multiple mechanisms involving soluble, colloidal, and crystalline urate salts. Uric acid is the instigator of the crime. The third and least common condition involves urate as an integral part of the urolith as an ammonium salt driven by high ammonium and high urate concentrations in urine. Here, uric acid is one of the perpetrators of the crime. Both known and postulated pathogenesis of these three types of urolithiasis are reviewed and summarized.