New findings challenge a prevailing belief that higher urine uric acid excretion increases the risk for calcium oxalate stone formation, according to researchers.
In fact, investigators found that urinary uric acid had a significant inverse association with stone formation in men, a marginal inverse association in younger women, and no association in older women, according to a report in Kidney International (2008; published online ahead of print).
The researchers, Gary C. Curhan, MD, ScD, and Eric N. Taylor, MD, of the Channing Laboratory and the Brigham and Women’s Hospital in Boston, noted that some studies have suggested that “urine uric acid, at least in the hyperuricosuric range, is an important risk factor for calcium oxalate stone formation, despite the lack of a clear mechanism.”
The authors pointed out, however, that “most of these studies were small, included relatively few controls, and did not take into account other urinary factors correlated with hypuricosuria, such as urine oxalate.”
In their study, Drs. Curhan and Taylor examined 24-hour urine excretion and the risk of being a kidney stone former in 3,350 men and women, of whom 2,237 had a history of nephrolithiasis. The study population consisted of 1,301 participants (898 stone formers and 403 controls) in the Nurses’ Health Study I, which enrolled female nurses aged 30-55 in 1976; 999 participants (703 stone formers and 296 controls) in the Nurses’ Health Study II, which enrolled female nurses aged 25-42 in 1989; and 1,050 participants (636 stone formers and 414 controls) in the Health Professionals Follow-up Study, which enrolled male health professionals aged 40-75 in 1986.
Compared with men whose urine uric acid excretion was less than 400 mg/day, those whose urine uric acid excretion was 400-499, 500-599, 600-699, 700-799, and 800 mg/day or higher had a 52%, 51%, 59%, 62%, and 78% lower risk of kidney stone formation, respectively, according to the researchers. These analyses were adjusted for all urinary factors simultaneously to examine the independent association between the individual urinary factors and likelihood of being a stone former.
Additionally, they found that the risk of stone formation in all cohorts rose significantly with increasing urine calcium and oxalate, and decreased significantly with increasing citrate and urine volume, the study showed. Stone formation risk associated with urine calcium, and oxalate began to change significantly below traditional normal thresholds.
The researchers noted, for example, that an increase in risk begins to occur with urine calcium excretion of 150-199 mg/day. The most traditionally used threshold is 250 mg/day for women and 300 mg/day for men, but many laboratories and other research studies have used 250 mg/day for both genders or 200 mg/day for women and 250 mg/day for men, according to the researchers. As a result of the new study, current definitions of normal levels for urinary factors need to be re-evaluated.
The researchers observed that although current recommendations to reduce urine uric acid (such as decreasing purine intake, prescribing allopurinol) may help reduce the risk of recurrent stone formation, the mechanisms for these interventions may be independent of their uric acid lowering effect.