Non-linear dilution adjustment of exemplary urine arsenic Part I: Curving the lines

Abstract

AbstractBackgroundConventional dilution adjustment of spot urinary biomarkers by correction for creatinine (uCR, CCRC), osmolality, or specific gravity remains controversial. Apart from unaccounted confounders such as age, sex, muscle mass, or diet, the misperception of constant mass ratios between analyte and corrector over a wide hydration range entails deceptive correction errors foremost at both ends of the hydration spectrum. Mitigating creatinine-correction errors (CRCE) by restricting uCR ranges to 0.3 (0.4)-3 g/L generates high numbers of sample rejects and allows for misleading fluctuations within presumably tolerable uCR ranges, undermining the validity of clinical, forensic, and epidemiological investigations.MethodsThe CRCE for exemplary total weight arsenic (TWuAs) was analyzed in n= 5599 unselected spot urine samples. After confining data to 14 – 82 years, uncorrected arsenic (uAsUC) < 500 µg/l, and uCR < 4.5 g/L, the remaining 5400 samples were partitioned, and a calculation method to standardize uAsUCto 1 g/L uCR was developed based on uAsUC-stratified power functional regression analysis (PFRA).FindingsThe obtained standardizing method of variable power-functional creatinine correction (V-PFCRC) represents a progression of reportedly proven simple power-functional CCRC (S-PFCRC) modifications. In contrast to CCRC and S-PFCRC, standardization to 1 g/L uCR by V-PFCRC yielded constant uAsNvalues over the entire uCR range in all sextiles. Residual bias was largely neutralized in all sextiles of uAsN(R29E-06 – 0.04) compared to uAsUC(R20.93 – 0.99) and CCRC (R20.42 – 0.89). The strongest %CRCEs were found in samples at low concentrations of uCR (SBC −0.96) and/or uAsUC(SBC −0.11).InterpretationStandardization to 1 g/L uCR by V-PFRA allows for more reliable dilution adjustment of spot urinary results than CCRC and S-PFCRC. As an easily adoptable, novel approach, the calculation method developed in this study can minimize residual dilution bias in urinary biomarkers adjusted by uCR, SG, and osmolality. While minimizing sample rejects, V-PFCRC will improve reliability and comparability, particularly of lower concentrated urinary biomarkers in conventional readings and multiple linear regression models.