The main causes of chronic kidney disease (CKD) globally are diabetes and hypertension but epidemics of chronic kidney disease of unknown etiology (CKDu) occur in Central America, Sri Lanka, India and beyond. Althoug also being observed in women, CKDu concentrates among men in agricultural sectors. Therefore, suspicions fell initially on pesticide exposure, but currently chronic heat stress and dehydration are considered key etiologic factors. Responding to persistent community and scientific concerns about the role of pesticides, we performed a systematic review of epidemiologic studies that addressed associations between any indicator of pesticide exposure and any outcome measure of CKD. Of the 21 analytical studies we identified, seven were categorized as with low, ten with medium and four with relatively high explanation value. Thirteen (62%) studies reported one or more positive associations, but four had a low explanation value and three presented equivocal results. The main limitations of both positive and negative studies were unspecific and unquantified exposure measurement ('pesticides'), the cross-sectional nature of most studies, confounding and selection bias. The four studies with stronger designs and better exposure assessment (from Sri Lanka, India and USA) all showed exposure-responses or clear associations, but for different pesticides in each study, and three of these studies were conducted in areas without CKDu epidemics. No study investigated interactions between pesticides and other concommittant exposures in agricultural occupations, in particular heat stress and dehydration. In conclusion, existing studies provide scarce evidence for an association between pesticides and regional CKDu epidemics but, given the poor pesticide exposure assessment in the majority, a role of nephrotoxic agrochemicals cannot be conclusively discarded. Future research should procure assessment of lifetime exposures to relevant specific pesticides and enough power to look into interactions with other major risk factors, in particular heat stress.
Keywords: Agrochemicals; Chronic kidney disease of unknown etiology (CKDu); Etiology; Exposure; Pesticides; Review.