Variable power functional dilution adjustment of spot urine.

Spot-urinary biomarkers are crucial in medical, epidemiological, and environmental studies, but their variability due to hydration levels requires precise dilution adjustments. Traditional methods, like conventional creatinine correction (CCRC), are limited in compensating for variations in urine concentration, causing substantial inconsistencies, particularly at the extremes of the diuresis spectrum. While restricting the creatinine (CRN) range to 0.3-3 g/L is recommended to ensure result stability, this approach excludes a substantial proportion of samples and permits notable fluctuations within the accepted range. This study introduces a novel variable power functional creatinine correction method (V-PFCRC) to normalize analytes to 1 g/L CRN by utilizing uncorrected analyte levels and two analyte-specific coefficients, c and d. Based on extensive urinary total weight arsenic data (n = 5,553), the mathematical derivation of these coefficients is detailed in this paper and forms the foundation of the corrective V-PFCRC formulas. The generalizability of V-PFCRC was evaluated using large spot-urinary datasets for four additional metals and an extensive dataset of urinary iodine levels (n > 58,000) and blood iodine. Validation against conventional methods-assessing vital statistical data, residual CRN bias, and correlations with concurrently detected blood levels of total arsenic and iodine- demonstrated the superior performance of V-PFCRC in reducing residual CRN bias and enhancing blood-urine correlations. The V-PFCRC method effectively addresses nonlinear hydration bias and the exposure-dependent variability of this bias, providing a more accurate representation of exposure and supply levels. The adaptability and efficiency of V-PFCRC suggest its broad applicability across various scientific disciplines, potentially transforming the precision and reliability of urinary biomarkers.