Variable Power Functional Dilution Adjustment of Spot Urine

Spot-urinary biomarkers are essential for medical, epidemiological, and environmental research. However, they are affected by hydration-dependent diuresis, requiring precise dilution adjustments. Traditional methods, like conventional creatinine correction (CCRC), have limitations and introduce errors due to residual diuresis dependence. To address this, the WHO recommends a valid creatinine (CRN) range of 0.3-3 g/L. The present study introduces a novel numerical variable power functional CRN correction method (V-PFCRC). It was developed using 5553 spot urinary samples for total weight arsenic from a diverse population with generally low background exposure to inorganic arsenic from drinking water. The innovative V-PFCRC formula normalizes analytes (A) to 1 g/L CRN using uncorrected analyte levels and two analyte-specific coefficients, c and d: A normalized = A uncorrected / CRN[c · Ln(A uncorrected) + d] / [c · Ln(CRN) + 1]When applied to spot urinary arsenic, iodine, cesium, molybdenum, strontium, and zinc, the V-PFCRC method significantly reduced residual CRN bias. It performed better compared to uncorrected, conventionally (CCRC), and simple power functionally CRN-corrected (S-PFCRC) urine samples. V-PFCRC enhanced CRN-bias removal in entire datasets and within seven separately analyzed analyte levels (septiles), adequately compensating for non-linear, exposure-differentiated skews, including complex metabolic and excretory interactions between analytes and CRN. These advancements were supported by improved blood-urine correlations for iodine and arsenic in both sexes, suggesting a more accurate representation of supply and exposure than traditional urinary dilution corrections. The results underscore the superior performance of the V-PFCRC method in adjusting for hydration-dependent variability, surpassing traditional correction methods. The resource-efficient and versatile V-PFCRC method is easy to implement and holds immense potential for broader applications in various scientific and medical fields. This study advocates for the wider adoption of V-PFCRC to enhance the accuracy and reliability of urinary biomarkers, ensuring superior diagnostic and research outcomes. Keywords: Non-linear dilution adjustment, variable power-functional dilution adjustment, creatinine correction, spot urine, biomarkers, arsenic, iodine, metal analytics, exposure studies.