Association between organophosphorus flame retardant exposure and chronic kidney disease in U.S. adults: NHANES data from 2011 to 2016

As alternatives to brominated flame retardants, Organophosphorus Flame Retardants (OPFRs) have raised concerns regarding their potential nephrotoxicity. However, population-based evidence remains inconsistent. This study aimed to examine the associations between urinary metabolites of OPFRs and Chronic Kidney Disease (CKD), along with renal function markers (estimated Glomerular Filtration Rate [eGFR] and the urinary Albumin‒Creatinine Ratio [ACR]), in the general U.S. population while exploring potential underlying mechanisms. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2011–2016, which included 2156 adults. Five OPFR metabolites, including Diphenyl Phosphate (DPHP), Bis(1,3-dichloro-2-propyl) Phosphate (BDCPP), Bis(1-chloro-2-propyl) Phosphate (BCPP), Bis(2-chloroethyl) Phosphate (BCEP), and Dibutyl Phosphate (DBUP), were measured in the urine. Multivariate logistic regression, subgroup analyses, Restricted Cubic Spline (RCS), and Weighted Quantile Sum (WQS) regression were performed, with CKD defined as an eGFR < 60 mL/min/1.73 m 2 or an ACR ≥ 30 mg/g. BCPP was inversely associated with CKD risk (Q4 vs. Q1: OR = 0.42, 95% CI 0.23–0.77, P = 0.007), particularly in hypertensive, elderly, and high-income populations. DPHP and BDCPP were significantly positively correlated with the eGFR (P for trend < 0.05), although the association weakened after adjustment. DBUP exhibited an inverted U-shaped relationship with the eGFR ( P -nonlinear = 0.048). WQS analysis indicated that OPFR mixtures were associated with higher eGFRs ( β = 1.20, 95% CI 0.38–2.02, P = 0.004), which was driven primarily by DBUP and DPHP. Our analysis reveals complex, non-monotonic associations between OPFR metabolites and renal function in U.S. adults, presenting a challenge to the prevailing assumption of linear nephrotoxicity. The observed associations warrant cautious interpretation due to potential reverse causality, underscoring the complexity of low-dose exposure assessment and the need for refined risk assessment frameworks.