Risk factors for chronic kidney disease of non-traditional causes: a systematic review

Objectives: To evaluate the potential associations between chronic kidney disease of uncertain or non-traditional etiology (CKDnT) and agrochemicals, heat stress, heavy metals, and other factors identified in the literature in any region of the world and at any time. Methods: This was a systematic review of the most frequent exposures suspected to be possible causes of CKDnT. A search was conducted of PubMed, LILACS, World Wide Science electronic databases, among other sources. Only medium- and high-quality studies were included. The synthesis of evidence included a narrative synthesis, meta-analysis, and meta-regression. Results: Four systematic reviews and 61 primary studies were included. Results of the meta-analysis suggest that exposure to agrochemicals and working in agriculture increase the risk of CKDnT, but this only reached significance for working in agriculture. When cross-sectional studies were excluded, agrochemical exposure became significant. However, there is substantial heterogeneity in the effect sizes. Conclusions: Based on the existing evidence and the precautionary principle, it is important to implement preventive measures to mitigate the damage caused by CKDnT to both agricultural workers and their communities (i.e., improvement of working conditions, cautious management of agrochemicals, etc.). More high-quality research is needed to measure impact and to build the evidence base