Adjustment for body mass index and calcitrophic hormone levels improves the diagnostic accuracy of the spot urine calcium-to-creatinine ratio

Abstract

Providers diagnose hypercalciuria using a 24-hour or random urine samples. We compared calcium measurements from paired 24-hour and morning urine samples; measurements correlated poorly. We developed a formula to correct random urine calcium levels. Corrected levels showed excellent agreement with 24-hour measurements. Until validation, providers should diagnose hypercalciuria using 24-hour tests. Hypercalciuria is a risk factor for osteoporosis and nephrolithiasis. The 24-hour urine calcium (24HUC) measurement is the gold standard to diagnose hypercalciuria, but the spot urine calcium-to-creatinine ratio (SUCCR) is more convenient. Although authors claim they are interchangeable, we observed inconsistencies during the conduct of a clinical trial. Therefore, we systematically evaluated agreement between the tests. During a 28-inpatient calcium absorption studies in 16 postmenopausal women, we simultaneously collected paired fasting morning and 24-hour urine specimens. We found moderate correlation between paired SUCCR and 24HUC specimens (r = 0.57, p = 0.002), but the SUCCR underestimated 24HUC by a mean of 83 mg (Bland-Altman). We diagnosed hypercalciuria (24HUC >250 mg) in eight specimens using the 24HUC, but only in two specimens using the SUCCR (25% sensitivity). We developed a regression model to predict 24HUC using SUCCR, parathyroid hormone, body mass index, and 1,25(OH)(2)D. The model improved diagnostic sensitivity to 100% and decreased Bland-Altman bias of the SUCCR to +0.06 mg/kg/24-hour. We conclude that the SUCCR underestimates urine calcium loss and does not reliably diagnose hypercalciuria. A formula derived from multivariate regression incorporating other readily measurable variables greatly improved the SUCCR's accuracy. Future studies must verify this correction before clinical implementation.