Association of cadmium environmental exposure with chronic kidney disease: A systematic review and meta-analysis

Background: Several observational studies investigated the relationship between environmental cadmium exposure and risk of chronic kidney disease (CKD). However, results from epidemiological studies are conflicting and wide variabilities have been reported. Objectives: We conducted a meta-analysis to evaluate the relationship between environmental cadmium exposure and CKD risk, as assessed by decreased estimated Glomerular Filtration Rate (eGFR) in adults. Methods: PubMed, Embase and the Cochrane library databases were searched for studies published up to July 2023. A random-effects model using the restricted maximum likelihood (REML) method was used to calculate the overall estimate to assess the association between cadmium exposure and eGFR. Subgroup analysis, funnel plot, Egger's test, and the trim-and-fill method were also conducted. Results: Thirty-one articles, 3 cohorts, 2 case-control and 26 cross-sectional studies, across 8 countries, involving 195.015 participants were included. The meta-analysis demonstrated an inverse association between high cadmium exposure and eGFR levels (standardized regression coefficient β = -0.09; 95 % CI = -0.15, -0.04). The subgroup analysis showed that the inverse association was significantly higher for blood cadmium exposure (β = -0.12; 95 % CI = -0.18, -0.06) than for urinary concentrations (β = -0.04; 95 % CI: -0.10, 0.03) or dietary exposure (β = -0.03; 95 % CI = -0.19, 0.14). Stratified analysis by different study design also showed an inverse association between cadmium exposure and eGFR, more evident in the cross-sectional studies (β = -0.11; 95 % CI = -0.18, -0.03) than in the cohort (β = -0.05; 95 % CI = -0.26, 0.17) and in the case-control studies (β = -0.05; 95 % CI = -0.32, 0.21). Discussion: Our meta-analysis indicated that environmental cadmium exposure is associated with increased risk of CKD, as assessed by decreased eGFR, and this association is more evident for blood cadmium concentrations than for urinary concentrations or dietary exposure. Nevertheless, additional high quality prospective studies are needed to confirm the association between cadmium exposure and risk of CKD.