Chronic kidney disease of unknown etiology in Nicaragua: investigating the role of environmental and occupational exposures

Background: In Central America, an epidemic of chronic kidney disease (CKD) primarily affects younger, male agricultural workers. Hypothesized causal agents include heat stress, agrichemicals, and heavy metals, among others, but the etiology remains unknown. Our aims were to assess job-specific changes in kidney function and injury during the sugarcane harvest season, characterize hydration practices and metals exposure, and determine whether these agents are associated with kidney function and injury. The overall goal was to address this public health emergency to inform intervention and prevention strategies. Methods: We recruited 284 sugarcane workers, representing seven job tasks, and 51 miners, all from northwestern Nicaragua. We sampled sugarcane workers at two time points (before and near the end of the harvest season) and miners at one time point. As a marker of kidney function, we measured serum creatinine to estimate glomerular filtration rate (eGFR). As markers of kidney injury, we measured urinary neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), N-acetyl-D-glucosaminidase (NAG), albumin, and creatinine. We measured blood lead and urinary cadmium, uranium, and total arsenic in a subset of sugarcane workers and miners. Results: Kidney function (eGFR) declined during the harvest season in seed cutters, irrigators, and cane cutters compared to other jobs, and kidney injury biomarkers (NGAL, IL-18) increased during the harvest, most notably among cane cutters. Electrolyte solution consumption appeared protective in cane cutters, a job with high heat exposure and heavy manual exertion. Though metal biomarkers were not elevated, there was some evidence that combined exposure to multiple metals was associated with decreased kidney function and increased injury. Albuminuria was rare. Conclusions: These findings provide evidence that occupational exposures are involved in the etiology of CKD. Heat stress and volume depletion may play a role, most likely in combination with one or more other agents, possibly environmental exposure to low-level metals. Our results do not support the hypothesis that agrichemicals are causal, but future studies that quantify exposure to specific agents are needed. The limited albuminuria and presence of tubular injury markers supports a tubulointerstitial disease that could occur with repeated subclinical injury leading to clinically apparent CKD over time