Background 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. Methods We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2011--2016, which included 2,156 adults. Five OPFR metabolites (DPHP, BDCPP, BCPP, BCEP, and 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 m² or an ACR ≥30 mg/g. Results 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. Conclusions Low-level OPFR exposure may be associated with a reduced risk of CKD, potentially through mitochondrial activation. These findings challenge the assumption of linear toxicity, highlight the complexity of dose‒response relationships, and underscore the need for further mechanistic validation and refined risk assessment frameworks.

Organophosphorus Flame Retardants, Chronic Kidney Disease, Renal Function Markers, Nonalotonic Dose‒Response