Mesoamerican nephropathy (MeN) is an endemic, non-diabetic, non-hypertensive chronic kidney disease (CKD) characterized by reduced glomerular filtration rate (GFR) with mild or no proteinuria and no features of known primary glomerular diseases. MeN is prevalent in agricultural communities along the Pacific Ocean coastal lowlands Mesoamerica, including southern Mexico, Guatemala, El Salvador, Nicaragua, Honduras and Costa Rica. Although most cases have been described among agricultural workers, MeN has also been described in other occupations, including miners, brick manufacturers, and fishermen. A common denominator among these occupations is that they are outdoor workers who reside in rural areas in hot and humid climates. The MeN epidemic in Central America extends along a nearly 1000 kilometer stretch of the Pacific coast. Among the countries that this span encompasses, CKD is the second leading cause of death in El Salvador and Nicaragua, third leading cause in Costa Rica, and fourth leading cause in Panama. El Salvador and Nicaragua have the highest rates of kidney disease mortality in the world; among men, the mortality rate from CKD is approximately six-fold higher in El Salvador and five-fold higher in Nicaragua than the median global rate, and 1.5-2 times higher than the rate in Libya, the third-highest country on the list. The disease has devastated many of the communities where it exists and has overwhelmed healthcare systems in affected countries, causing unknown morbidity and tens of thousands of deaths over the last 20 years in Mesoamerica alone. MeN is generally diagnosed in men in their twenties or thirties, and initially presents as a progressive decline in GFR without notable proteinuria. Traditional risk factors for CKD, including hypertension and diabetes mellitus, are generally absent. Despite international research efforts, the specific causes of the disease remain unknown, creating an enormous need for research, patient care and socioeconomic interventions that can only be appropriately addressed through international and interdisciplinary collaboration. The term Mesoamerican Nephropathy has been in use in Central America and Mexico since 2012. Similar epidemics have been identified in both Sri Lanka and India, leading to the use of other terms that are not geographically specific, including Chronic Kidney Disease of unknown etiology (CKDu) or of non-traditional origin (CKDnt) and Chronic Interstitial Nephritis in Agricultural Communities (CINAC). Although the diseases are clinically similar and affect similar populations in each country, whether these are all manifestations of the same disease or different diseases with superficial resemblance remains to be definitively demonstrated. High prevalence of CKD with similar characteristics to MeN may exist outside of Mesoamerica, India, and Sri Lanka, although evidence so far is limited to small studies and clinician reports.
Causes Although many factors have been proposed as the cause of MeN, most attention has focused on heat stress due to a combination of strenuous work in a hot climate with insufficient hydration. Additional postulated contributing exposures include agrochemicals, metals, and pathogens. These factors are themselves a result of global and national economic and political systems that have led to poverty and social stratification. Discovery of the causes of MeN has been complicated by the fact that there are likely multiple factors that arise from different sources of exposure and/or different times of life. Until recently, progress has also been slowed by a lack of research funding, although more support has become available as awareness of the disease and its toll on the population has increased. A review published in the New England Journal of Medicine in 2019 summarizes a proposed mechanism in which heat exposure leads to dehydration and volume depletion and/or an increase in core temperature, which may cause kidney injury directly through tissue dysfunction or indirectly through hyperosmolarity or rhabdomyolysis. Similarly, it is possible that chronic sub-clinical undetected AKI leads to eventual CKD. Another proposed mechanism is increased kidney tubular toxin uptake resulting in direct tubular toxicity, which might also be amplified by heat-associated dehydration. Genetic factors are also likely to play a role. Regardless of what mechanisms are eventually proven to be involved, researchers agree that preventive measures should include measures to ensure safe drinking water, adequate hydration, rest, and shade for workers at risk, as well as to reduce exposure to toxins. A review of the state of knowledge on potential causes and mechanisms as of 2019 can be found in a summary of the Third International Workshop on Chronic Kidney Disease of Uncertain/Non-Traditional Etiology in Mesoamerica and Other Regions on Chronic Kidney Disease of Unknown Etiology held in March 2019.
… excerpt ends here. Continue reading the full article.
