The general external exposome and the development or progression of chronic kidney disease: a systematic review and meta-analyses

The impact of environmental risk factors on chronic kidney disease (CKD) remains unclear. This systematic review aims to provide an overview of the literature on the association between the general external exposome and CKD development or progression. We searched MEDLINE and EMBASE for case-control or cohort studies, that investigated the association of the general external exposome with a change in eGFR or albuminuria, diagnosis or progression of CKD, or CKD-related mortality. The risk of bias of included studies was assessed using the Newcastle-Ottawa Scale. Summary effect estimates were calculated using random-effects meta-analyses. Most of the 66 included studies focused on air pollution (n=33), e.g. particulate matter (PM) and nitric oxides (NOx), and heavy metals (n=21) e.g. lead and cadmium. Few studies investigated chemicals (n=7) or built environmental factors (n=5). No articles on other environment factors such as noise, food supply, or urbanization were found. PM2.5 exposure was associated with an increased CKD and end-stage kidney disease incidence, but not with CKD-related mortality. There was mixed evidence regarding the association of NO 2 and PM10 on CKD incidence. Exposure to heavy metals might be associated with an increased risk of adverse kidney outcomes, however, evidence was inconsistent. Studies on effects of chemicals or built environment on kidney outcomes were inconclusive. In conclusion, prolonged exposure to PM2.5 is associated with an increased risk of CKD incidence and progression to kidney failure. Current studies predominantly investigate the exposure to air pollution and heavy metals, whereas chemicals and the built environment remains understudied. Substantial heterogeneity and mixed evidence were found across studies. Therefore, long-term high-quality studies are needed to elucidate the impact of exposure to chemicals or other (built) environmental factors and CKD.