Non-linear dilution adjustment of exemplary urine arsenic Part II: Sex- and Age-specific Differences

Abstract

AbstractBackgroundIn the first part of this study, a variable power-functional creatinine correction (V-PFCRC), normalizing results to 1 g/L creatinine (uCR), was established for total weight spot-urinary arsenic (TWuAs) as an adequate method of urinary dilution. In this second part, the impact of age and sex on TWuAs, V-PFCRC functions, and fluid regulation was investigated in the identical dataset of the first part based on a comprehensive literature review.MethodsAll samples with age indication, uAsUC≤ 500 mg/L, and uCR < 4.5 g/L (n=5585, females n= 2967, males n = 2618) were classified into seven age groups, for which sex-aggregate and disaggregate means ± SEs, medians, and ICRs were calculated for uCR and TWuAs in uncorrected (uAsUC), classical CR corrected (CCRC, uAsC), and V-PFCRC (uAsN) results mode. In addition, Pearson correlation analyses were performed for uCR and TWuAs with age. In addition, sex-aggregated and disaggregated V-PFCRC functions were compared between three numerically similar age groups. Finally, the efficacy of creatinine correction error (CRCE) compensation was assessed by simple power-functional regression analysis (PFRA) in both sexes and seven age bands.FindingsThe clear male dominance of uAsUC(p < 0.001) in aggregate age data and all five adult subgroups separately was inverted by CCRC (uAsC, p = 0.011) and neutralized by V-PFCRC (uAsN, p = 0.19). Children and adolescents did not exhibit significant sex variations in TWuAs or uCR. A continuous rise in TWuAs with age from adolescence to the beginning of the seventh decade of life was observed in uAsUC, uAsC,and uAsN(0.28 µg/1 g uCR/year). Conversely, TWuAs decreased from childhood to adolescence and in the highest age group. Pearson analysis for all patients between 14 - 72 years and uAsUC≤ 500 μg/L revealed significant weak positive correlations (p < 0.001) between TWuAs and age. The log curves between the coefficienta(= uAsN) and exponentbran higher in younger men and both sexes among seniors, in broad analogy with reportedly higher baseline renal vasopressor activities of angiotensin II (ATII) and arginine vasopressin (AVP, V1) in these subgroups. The efficacy of V-PFCRC was established based on minimized residual biases of uCR on uAsNin both sexes and all seven age bands (R20.0029 - 7.0E-09).InterpretationSex differences in uAsUC and uAsC are primarily attributable to distinct urinary dilution and thus are compensated by V-PFCRC. In contrast, age-dependent increases in TWuAs, evident in all results modes, are genuine and should be further accounted for in exposure studies and normal range determinations. While sex and age affect V-PFCRC formulas analog to baseline vasopressor activities of ATII/AVP, they only negligibly affect the correction validity. Adequate perception of power-functional relations between uCR and uAsUCalone, even neglecting these minor sex- and age-specific differences in V-PFCRC correction formulas, results in substantial improvement of dilution adjustment.