Is an Environmental Nephrotoxin the Primary Cause of CKDu (Mesoamerican Nephropathy)? CON

Abstract

Over the last three decades, tens of thousands of premature deaths due to CKD of nontraditional origin (CKDnt) (The Pan-American Health Organization recommends the use of CKDnt in the Americas (1) https://www.paho.org/hq/dmdocuments/2015/CE156-INF-8-e.pdf and I use this term in this document) have occurred in Mesoamerica’s Pacific coastal areas, the Northern Central Province of Sri Lanka, and Uddanam, India. Toxins and occupational heat stress are the two main hypotheses for primary causes (2,3). I present arguments in favor of a heat stress nephropathy in contrast to a toxic nephropathy. My case is presented on the basis of ( 1 ) the need for well designed epidemiologic studies, ( 2 ) the reasons why a primary toxic cause of CKDnt is unlikely, and ( 3 ) a summary of the evidence for occupational heat stress as the prime driver of CKDnt in Mesoamerica, recognizing that heat stress has not yet been explored in Sri Lanka or India (Table 1). View this table: Table 1. Arguments at a glance Finding a cause for an epidemic is a different research scenario from establishing associations between hazards and subtle disease occurrence. An epidemic implies many affected people and a strong driver, be it a biologic, chemical, or physical hazard. Any presumed risk factor must be highly prevalent in the most affected subpopulations and be specific to them. To unravel the cause of the CKDnt epidemics, well designed epidemiologic prevalence and analytical studies are essential, revealing the distribution of CKDnt in different populations and linking adequate exposure data of any potential hazard to the disease’s occurrence. Epidemiology should be consistent with social science, physiology, toxicology, and pathology studies, but without documented epidemiologic associations no reasonable causal assertions can be drawn. Although seemingly obvious, when it comes to providing proof of CKDnt cause such principles are often overlooked. Solid epidemiologic research has been mostly developed …

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