Praxis Dr. Carmine, Pfaeffikon SZ, Switzerland.
BMC Nephrol. 2024 Oct 13;25(1):348. doi: 10.1186/s12882-024-03758-w.
Previous research introduced V-PFCRC as an effective spot urinary dilution adjustment method for various metal analytes, including the major environmental toxin arsenic. V-PFCRC normalizes analytes to 1 g/L creatinine (CRN) by adopting more advanced power-functional corrective equations accounting for variation in exposure level. This study expands on previous work by examining the impacts of age and sex on corrective functions.
Literature review of the effects of sex and age on urinary dilution and the excretion of CRN and arsenic. Data analysis included a Data Set 1 of 5,752 urine samples and a partly overlapping Data Set 2 of 1,154 combined EDTA blood and urine samples. Both sets were classified into age bands, and the means, medians, and interquartile ranges for CRN and TWuAs in uncorrected (UC), conventionally CRN-corrected (CCRC), simple power-functional (S-PFCRC), sex-aggregated (V-PFCRC SA), and sex-differentiated V-PFCRC SD modes were compared. Correlation analyses assessed residual relationships between CRN, TWuAs, and age. V-PFCRC functions were compared across three numerically similar age groups and both sexes. The efficacy of systemic dilution adjustment error compensation was evaluated through power-functional regression analysis of residual CRN and the association between arsenic in blood and all tested urinary result modes.
Significant sex differences in UC and blood were neutralized by CCRC and reduced by V-PFCRC. Age showed a positive association with blood arsenic and TWuAs in all result modes, indicating factual increments in exposure. Sex-differentiated V-PFCRC best matched the sex-age kinetics of blood arsenic. V-PFCRC formulas varied by sex and age and appeared to reflect urinary osmolality sex-age-kinetics reported in previous research. V-PFCRC minimized residual biases of CRN on TWuAs across all age groups and sexes, demonstrating improved standardization efficacy compared to UC and CCRC arsenic.
Sex differences in UC and CCRC arsenic are primarily attributable to urinary dilution and are effectively compensated by V-PFCRC. While the sex and age influence on V-PFCRC formulas align with sex- and age-specific urinary osmolality and assumed baseline vasopressor activities, their impact on correction validity for entire collectives is minimal.
The V-PFCRC method offers a robust correction for urinary arsenic dilution, significantly reducing systemic dilution adjustment errors. Its application in various demographic contexts enhances the accuracy of urinary biomarker assessments, benefiting clinical and epidemiological research. V-PFCRC effectively compensates for sex differences in urinary arsenic. Age-related increases in TWuAs are exposure-related and should be additionally accounted for by algebraic normalization, covariate models, or standard range adjustments.
先前的研究引入了 V-PFCRC，作为一种针对各种金属分析物（包括主要环境毒素砷）的有效尿液点稀释调整方法。V-PFCRC 通过采用更先进的幂函数校正方程，将分析物标准化为 1g/L 肌酐（CRN），以适应暴露水平的变化。本研究通过研究年龄和性别对校正函数的影响，扩展了先前的工作。
对性别和年龄对尿液稀释和 CRN 和砷排泄的影响进行文献回顾。数据分析包括 5752 个尿液样本的数据集 1 和 1154 个 EDTA 血液和尿液样本的部分重叠数据集 2。这两个数据集都按年龄带分类，比较了未校正（UC）、常规 CRN 校正（CCRC）、简单幂函数（S-PFCRC）、性别聚集（V-PFCRC SA）和性别区分 V-PFCRC SD 模式下的 CRN 和 TWuAs 的均值、中位数和四分位距。相关性分析评估了 CRN、TWuAs 和年龄之间的剩余关系。在三个数值相似的年龄组和两个性别组之间比较了 V-PFCRC 函数。通过对残留 CRN 的幂函数回归分析以及血液和所有测试尿液结果模式之间的砷关联，评估了系统稀释调整误差补偿的效果。
UC 和血液中的显著性别差异被 CCRC 中和，被 V-PFCRC 减少。年龄与所有结果模式中的血液砷和 TWuAs 呈正相关，表明实际暴露量增加。性别区分的 V-PFCRC 最好地匹配了血液砷的性别年龄动力学。V-PFCRC 公式因性别和年龄而异，似乎反映了先前研究中报告的尿液渗透压性别年龄动力学。V-PFCRC 最大限度地减少了 UC 和 CCRC 砷在所有年龄组和性别的 CRN 对 TWuAs 的残留偏差，与 UC 和 CCRC 砷相比，标准化效果得到了改善。
UC 和 CCRC 砷的性别差异主要归因于尿液稀释，V-PFCRC 有效地补偿了这些差异。虽然 V-PFCRC 公式对性别和年龄的影响与性别和年龄特异性尿液渗透压和假设的基础加压素活性一致，但它们对整个群体的校正有效性的影响很小。
V-PFCRC 方法为尿液砷稀释提供了一种强大的校正方法，显著降低了系统稀释调整误差。它在各种人口统计学背景下的应用增强了尿液生物标志物评估的准确性，使临床和流行病学研究受益。V-PFCRC 有效地补偿了尿液砷的性别差异。与年龄相关的 TWuAs 增加与暴露有关，应通过代数归一化、协变量模型或标准范围调整来进一步考虑。
