Urine Dilution Correction Methods Utilizing Urine Creatinine or Specific Gravity in Arsenic Analyses: Comparisons to Blood and Water Arsenic in the FACT and FOX Studies in Bangladesh

Abstract

Urinary As (uAs) is a biomarker of As exposure. Urinary creatinine (uCr) or specific gravity (SG) are used to correct uAs for urine dilution. However, uCr is correlated with As methylation, whereas SG has limitations in individuals with kidney damage. We aimed to evaluate which urine dilution correction methods for uAs most accurately predicted blood As (bAs). We used data from the Folic Acid and Creatine Trial (FACT; N = 541) and Folate and Oxidative Stress (FOX; N = 343) study in Bangladesh. Three linear regression models were assessed using uAs (1) adjusted for uCr or SG as separate covariates, (2) standardized for uCr or SG, i.e., uAs/uCr, and (3) adjusted for residual corrected uCr or SG following adjustment for age, sex and BMI. Median uAs/bAs for FACT and FOX were 114/8.4 and 140/12.3 µg/L. In FACT, two-fold increases in uAs adjusted for uCr or SG were related to 34% and 22% increases in bAs, respectively, with similar patterns in FOX. Across methods, models with uCr consistently had lower AIC values than SG. The uAs associations with bAs were stronger after adjustment for uCr vs. SG. Decisions regarding urine dilution methods should consider whether the study outcomes are influenced by factors such as methylation or medical conditions.