Twenty-four–hour urine chemistries and the risk of kidney stones among women and men

Abstract

BACKGROUND: Results of a 24-hour urine collection are integral to the selection of the most appropriate intervention to prevent kidney stone recurrence. However, the currently accepted definitions of normal urine values are not firmly supported by the literature. In addition, little information is available about the relationship between risk of stone formation and the levels of urinary factors. Unfortunately, the majority of previous studies of 24-hour urine chemistries were limited by the inclusion of recurrent stone formers and poorly defined controls. METHODS: We obtained 24-hour urine collections from 807 men and women with a history of kidney stone disease and 239 without a history who were participants in three large ongoing cohort studies: the Nurses' Health Study I (NHS I; mean age of 61 years), the Nurses' Health Study II (NHS II; mean age of 42 years), and the Health Professionals Follow-up Study (HPFS; mean age of 59 years). RESULTS: Mean 24-hour urine calcium excretion was higher and urine volume was lower in cases than controls in NHS I (P < or = 0.01), NHS II (P < or = 0.13) and HPFS (P < or = 0.01), but urine oxalate and citrate did not differ. Among women, urine uric acid was similar in cases and controls but was lower in cases in men (P = 0.06). The frequency of hypercalciuria was higher among the cases in NHS I (P = 0.26), NHS II (P = 0.03), and HPFS (P = 0.02), but 27, 17, and 14% of the controls, respectively, also met the definition of hypercalciuria. The frequency of hyperoxaluria did not differ between cases and controls, but was three times more common among men compared with women. After adjusting for the other urinary factors, the relative risk of stone formation increased with increasing urine calcium levels and concentration in all three cohorts but not in a linear fashion. Compared with individuals with a urine calcium concentration of <75 mg/L, the relative risk of stone formation among those with a urine calcium concentration of > or =200 mg/L for NHS I was 4.34 (95% CI, 1.59 to 11.88), for NHS II was 51.09 (4.27 to 611.1), and for HPFS was 4.30 (1.71 to 10.84). There was substantial variation in the relative risks for stone formation for the concentration of other urine factors within the different cohorts. CONCLUSIONS: The traditional definitions of normal 24-hour urine values need to be reassessed, as a substantial proportion of controls would be defined as abnormal, and the association with risk of stone formation may be continuous rather than dichotomous. The 24-hour urine chemistries are important for predicting risk of stone formation, but the significance and the magnitudes of the associations appear to differ by age and gender.