Mesoamerican nephropathy: A silent epidemic at the nexus of climate, labor, and health.

Mesoamerican nephropathy (MeN) has emerged as a critical yet often overlooked occupational and environmental health crisis. Primarily affecting young, otherwise healthy agricultural workers in Central America, this disease leads to rapid progression to kidney failure without traditional causes like diabetes or hypertension. While the central drivers are recurrent heat stress and chronic dehydration, emerging research reveals a multifactorial pathogenesis. This includes synergistic nephrotoxic insults from agrochemicals, heavy metals, chronic endotoxin exposure, and mycotoxins (e.g., ochratoxin A). Morphologic studies point to shared pathways of tubular injury, characterized by mitochondrial dysfunction and lysosomal abnormalities. Furthermore, gut-kidney crosstalk and genetic susceptibility, particularly among individuals with Native American ancestry, may amplify renal inflammation and injury. Although targeted interventions, such as enhanced hydration, rest, and access to shade, show promise, their efficacy in halting disease progression remains limited. As global temperatures rise, similar disease patterns are now being reported among outdoor laborers in other hot regions, signaling a broader climate-linked public health threat. Addressing MeN demands a concerted, multidisciplinary effort encompassing rigorous pathogenesis research, enforceable occupational protections, and global recognition of heat-associated kidney disease as a growing epidemic. This perspective synthesizes recent insights into MeN and calls for urgent, actionable measures to confront this silent crisis.