The death toll of the epidemic of chronic kidney disease of nontraditional origin (CKDnt) in Mesoamerica runs into the tens of thousands, affecting mostly young men. There is no consensus on the etiology. Anecdotal evidence from the 1990s pointed to work in sugarcane; pesticides and heat stress were suspected. Subsequent population-based surveys supported an occupational origin with overall high male-female ratios in high-risk lowlands, but small sex differences within occupational categories, and low prevalence in non-workers. CKDnt was reported in sugarcane and other high-intensity agriculture, and in non-agricultural occupations with heavy manual labor in hot environments, but not among subsistence farmers. Recent studies with stronger designs have shown cross-shift changes in kidney function and hydration biomarkers and cross-harvest kidney function declines related to heat and workload. The implementation of a water-rest-shade intervention midharvest in El Salvador appeared to halt declining kidney function among cane cutters. In Nicaragua a water-rest-shade program appeared sufficient to prevent kidney damage among cane workers with low-moderate workload but not among cutters with heaviest workload. Studies on pesticides and infectious risk factors have been largely negative. Non-occupational risk factors do not explain the observed epidemiologic patterns. In conclusion, work is the main driver of the CKDnt epidemic in Mesoamerica, with occupational heat stress being the single uniting factor shown to lead to kidney dysfunction in affected populations. Sugarcane cutters with extreme heat stress could be viewed as a sentinel occupational population. Occupational heat stress prevention is critical, even more so in view of climate change.
