Association between exposure to arsenic, cadmium, and lead and chronic kidney disease: evidence from four practical statistical models

Environmental exposure to arsenic (As), lead (Pb) and cadmium (Cd) may cause chronic kidney disease (CKD), with varying independent effects and unclear combined impact. This study aimed to evaluate these effects on CKD.

1,398 individuals were included. Urine arsenic (UAs) was determined by atomic fluorescence method. Urinary cadmium (UCd) and blood lead (BPb) levels were determined by graphite-furnace atomic absorption spectrometry. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m² or proteinuria. Generalized linear models (GLM), restricted cubic spline (RCS) models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models were employed to study the independent and combined effects of exposure to As, Pb and Cd on CKD risk.

Compared with non-CKD subjects, UAs, UCd, BPb, and creatinine adjusted urinary cadmium (UCdCr) were all significantly higher in CKD subjects. Compared with the lowest quartiles, the ORs (95%CIs) of CKD risk in the highest quartiles were 2.09 (1.16–3.74) for UAs, 2.84(1.56–5.18) for UCd, and 1.79 (1.05–3.06) for UCdCr, respectively. UAs, UCd, and UCdCr were all significantly positively associated with CKD risk in p-trend tests. RCS models revealed non-linear links between UAs, UCd, UCdCr and CKD risk, while a linear dose–response existed for BPb and CKD risk. The OR (95%CI) in WQS models were 1.72 (1.25–2.36) with UAs being the highest weighing metal(loid). BKMR models showed co-exposure mixture linked to higher CKD risk when the ln-transformed metal(loid)s above their 55th percentile. The ln-transformed UAs and UCdCr was significantly positively associated with CKD risk when the other two ln-transformed metals levels were all fixed at their different percentile levels. Synergism between Cd and Pb was also apparent.

Single As, and Cd exposure were positively associated with an increased CKD risk. Co-exposure to As, Pb and Cd was positively associated with CKD risk, with As playing a dominant role.