Uric acid nephrolithiasis: Uric acid or urine pH?

The prevalence of uric acid nephrolithiasis in the general US population is approximately 8∈%. However, the prevalence of uric acid stones among diabetic and obese populations has been reported to be significantly high, approaching 3.5-fold greater than the general population. Although three main etiologic factors, including low urine volume, hyperuricosuria, and unduly urine acidity, have been implicated in the pathogenesis of uric acid nephrolithiasis, abnormal urine pH has been shown to play a key pathogenic role in uric acid precipitation and uric acid stone formation. Uric acid is a weak organic acid with an ionization constant (pKa∈=∈5.5); hence, at a urinary pH∈≤∈5.5 the urinary environment becomes supersaturated with highly insoluble undissociated uric acid, which greatly imposes the risk of uric acid development and precipitation. Under normal circumstances, uric acid solubility is limited to 96 mg/L; thus, humans with urinary uric acid excretion of approximately 600-800 mg/day must be at risk for uric acid precipitation. However, urinary pH plays a dominate role in keeping uric acid in the solution. Careful studies have demonstrated that at urinary pH between 6.2 and 6.4, the urinary environment becomes undersaturated with respect to undissociated uric acid content. Such an environment has been shown to be associated with a significantly reduced risk of uric acid stone formation. Given this predominate role of urinary pH, urinary uric acid must exceed 1,100 mg/day in order to promote uric acid precipitation. This condition rarely occurs in the majority of patients with idiopathic nephrolithiasis in whom urinary acid excretion was reported to be normal. Uric acid-lowering drugs must only be tried in some patients with primary gout, with genetic abnormalities in uric acid pathways including inborn errors in metabolism, uric acid metabolism, and those with accelerated tissue turnover.