BACKGROUND: The aim of this systematic review is to examine the epidemiological knowledge and gaps in understanding of the potential causes of chronic kidney disease of undetermined cause (CKDu) in Meso-America. METHODS: A systematic literature search of epidemiological studies of CKDu was conducted in PubMed, Embase and Web of Science from January 2000 to January 2017. Study quality was assessed by adapting the tool from Higgins et al. for observational studies. Where applicable, the summary prevalence odds ratio (POR) and 95% confidence interval (CI) were calculated using a random effects model. RESULTS: Twenty-five epidemiological studies were included in the analysis of risk factors for CKDu. The quality assessment of each occupational and community study was medium. The PORs for CKDu were males versus females 2.42 (95% CI 1.76-3.08), family history of CKD (versus none) 1.84 (95% CI 1.37-2.30), high water intake (versus low) 1.61 (95% CI 1.01-2.21) and low altitude (versus highland) 2.09 (95% CI 1.00-3.17). There were no significant associations between CKDu and pesticide exposure (versus no) 1.17 (95% CI 0.87-1.46), alcohol consumption (versus no) 1.34 (95% CI 0.84-1.84), non-steroidal anti-inflammatory drugs (versus no) 0.99 (95% CI 0.60-1.39) and heat stress (versus no) 1.52 (95% CI -0.91 - 3.95). CONCLUSION: Our meta-analysis showed positive associations for males (versus females) and family history of CKD, water intake, lowland altitude and CKDu. There were no significant associations with pesticide exposure, non-steroidal anti-inflammatory drugs intake, heat stress and alcohol consumption.