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Am J Trop Med Hyg. 2019 Sep;101(3):676-683. doi: 10.4269/ajtmh.18-0856.

Investigating Possible Infectious Causes of Chronic Kidney Disease of Unknown Etiology in a Nicaraguan Mining Community.

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Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts.
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts.
Division of Nephrology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts.
Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts.
Centers for Disease Control and Prevention, Atlanta, Georgia.


A chronic kidney disease of unknown etiology (CKDu) has been killing workers in Central America. Occupational heat stress is thought to play an important role. Leptospirosis and hantavirus have been suggested as additional possible risk factors. In a case-control study in a Nicaraguan mining community, a structured survey was administered to adults, and biological measurements and specimens were taken. Serum was analyzed for antibodies to Leptospira and hantavirus. Before statistical analysis, a board-certified nephrologist determined final case and control status based on serum creatinine and other laboratory values. Multivariable analysis was by logistic regression. In sensitivity analyses, cases were restricted to those diagnosed with CKDu in the previous 3 years. Of 320 eligible participants, 112 were classified as presumptive cases, 176 as controls and 32 as indeterminant. The risk of CKDu in those ever having worked in mining or construction was 4.4 times higher than in other participants (odds ratio = 4.44, 95% CI: 1.96-10.0, P = 0.0003). Eighty-three (26%) of the 320 participants were seropositive for at least one tested strain of Leptospira. No evidence of a causal link between leptospirosis or hantavirus and CKDu was found. The sensitivity analyses provide some evidence against the hypotheses that leptospirosis or hantavirus leads to CKDu within a few years. A major limitation was the impossibility of determining the absolute or relative timing of infection and CKDu onset. A prospective cohort design, with repeated collection of specimens over several years, could yield clearer answers about infections as potential etiologic agents in CKDu.

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