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

Oriana Ramírez-Rubio,Jessica H. Leibler,Renee L. Galloway,Damaris López-Pilarte,Alejandro Riefkohl,Juan José Amador,W. Katherine Yih,Daniel R. Brooks,David J. Friedman,Martin Kulldorff

doi:10.4269/ajtmh.18-0856

Abstract

.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.

Highlights

Since the mid-1990s or earlier, an epidemic of a chronic kidney disease of unknown etiology (CKDu) known as Mesoamerican nephropathy (MeN) has arisen in Pacific lowland areas from southern Mexico to Panama
The main objective of our study was to test the association between leptospirosis and evidence of reduced renal function in a region of Nicaragua heavily affected by MeN, but we investigated hantavirus exposure, self-reported occupational exposures, and other potential risk factors
In this study of 112 MeN cases and 176 controls in a mining area of Nicaragua, we found a high rate of Leptospira seropositivity among study participants but did not find a positive association between Leptospira seropositivity and MeN

Summary

Introduction

Since the mid-1990s or earlier, an epidemic of a chronic kidney disease of unknown etiology (CKDu) known as Mesoamerican nephropathy (MeN) has arisen in Pacific lowland areas from southern Mexico to Panama. Physical laborers such as sugarcane workers and miners, predominantly young and male, have been most affected.[1] The same or a similar disease has been noted among agricultural workers in Sri Lanka[2,3]; Andhra Pradesh, India[4,5]; and Egypt.[6] The risk profile of this disease of young workers, differs markedly from that of the well-characterized chronic kidney disease (CKD) associated with diabetes, obesity, and older age. The present epidemic in the Americas is estimated to have killed more than 20,000 people[10] and has deprived families of husbands, fathers, income, and savings, decimating whole communities

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