Out of the Ordinary: The Etiology of Mesoamerican Nephropathy

Written by: Aleeza Riaz

Edited by: Ray Zhang

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In 2002, a report from El Salvador stunned the global nephrology community. Among

young men from certain coastal areas, there was a high incidence of idiopathic, or spontaneously arising, chronic kidney disease (CKD) [1]. This mystifying condition, typically endemic to El Salvador’s west coast, was also prevalent in other agricultural populations in Central America. The proposed causes? Exposure to high temperatures, chronic dehydration, and genetics. The problem? This disease, markedly named Mesoamerican nephropathy (MeN), which is an epidemic of CKD, will only become more widespread in a warming climate [1, 2].

MeN, is a progressive form of tubulointerstitial nephritis, a condition in which the kidney filtering units become inflamed. The largest patient population for this disease is young agricultural workers. Laborers enter an active nephrological inflammatory phase due to chronic dehydration, strenuous working conditions, and the frequent use of painkillers to combat heat stroke [3]. The inflammation of kidney tubules—the constituents that are supposed to filter blood, return nutrients and fluids, remove waste, and maintain a healthy acid-base balance—consequently lowers kidney function [1, 3]. In addition, common agricultural pesticides can accumulate in the kidney tubules, further limiting their functions [3].

Despite these correlations, there is minimal literature on this potential factor for MeN. Laborers experience cramps, fever, and an average kidney function of less than 60% without the two typical risk factors of CKD––diabetes and hypertension––due to inflammation and tubular toxicity [1]. In addition, many patients present with unspecified symptoms of low-grade fever, proteinuria (protein in the urine), and/or dysuria (painful urination) [2]. However, an official diagnosis requires a kidney biopsy, a test that allows nephrologists to view the inflammation and tubular damage that characterize MeN’s tubulointerstitial nephritis [2].

In 2016, García-Trabanino et al. published a study utilizing data from a decade-long study from El Salvador’s Bajo Lempa rural coastal region. Fondo Social de Emergencia para la Salud (FSES) is a community-based approach for health services from which data from 2004 to 2013 was utilized. In this 10 year period, there were 271 cases of end-stage renal disease [4]. 75.5% of these patients worked or previously worked in agriculture, 66% did not have a history of diabetes or hypertension, and 97% were men [4]. This study from an area in which MeN is endemic represents the prevalence of the disease and its affliction of agricultural workers.

Scientists aim to solidify their understanding of the disease’s root causes with modern approaches. Researchers in Panama utilized whole exome sequencing, a test that sequences only the protein-coding regions of DNA to identify genetic variations, to investigate if there is a genetic implication in this condition. In a study of 61 patients with MeN, 16 individuals (26%) had a variant of the ApoE gene named ApoE4, or Rs429358 [5, 6]. This gene produces the apolipoprotein e, which can impact the progression of kidney disease by scarring smaller kidney filtration units, or glomeruli, with waste build-up. In 2025, Marín-Medina et al. utilized this study to elucidate that the Rs429358 variant is associated with hyperuricemia, or high uric acid levels [5]. Agricultural workers’, who are mostly affected by MeN, uric acid levels would spike and in conjunction with the genetic factor, an overwhelming amount of uric acid can peroxidate proteins and contribute to tubular injury [6]. Despite having a small sample size, scientists predict that genetics may play a key role in the etiology of MeN.

However, there is a more pressing issue that influences MeN: climate change. Since the

1970s, there has been a nine-fold increase in individuals with MeN, and now 13% to 18% of agricultural workers in El Salvador and Costa Rica have this disease [7]. In 2021, Boston University’s Zoe E. Peropolous et al. published research on Nicaragua’s maximum temperatures during the 1973 to 2014 harvest months and the number of days where the maximum temperature surpassed 35 ºC (95 ºF) [6]. Between 1973 and 1990, the average daily temperature during harvest season increased by 0.7 ºC (33 ºF) per decade [6]. In addition, the number of days per harvest season with a temperature above 35 ºC soared from 32 days to 114 [7]. While the daily maximum temperature decreased by 0.3 ºC per decade between 1991 and 2013, this region remains one of the hottest areas in the world [7].

High temperatures directly impact instances of dehydration. The fundamental principle surrounding dehydration is that the loss of water is greater than that for sodium [2]. As a result, there is an upsurge in uric acid levels, which stimulates inflammatory mediators and can impact glomerular filtration and tubules [2]. Increased electrolyte consumption, more break times for laborers, and higher levels of shade in working areas are potential treatments and preventions of MeN.

In a rapidly warming climate, communities across the world face unique challenges,

especially the resource-poor Mesoamerican Pacific lowlands. With the majority of communities dedicated to agricultural work, reduced kidney function afflicts at least 10% of men in regions

where MeN is prevalent. Inadequate access to healthcare prevents early intervention for MeN

and potential treatments, but it also hinders scientific research. The nephrology and research

worlds must not overlook these vulnerable Mesoamerican communities as climate change

continues to threaten public health.

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References

[1] García-Trabanino, Ramón, et al. “Incidence, Mortality, and Prevalence of End-Stage Chronic Renal Disease in the Bajo Lempa Region of El Salvador: A Ten-Year Community Registry.” Nefrología (English Edition), vol. 36, no. 5, Sept. 2016, pp. 517–522, https://doi.org/10.1016/j.nefroe.2016.11.006. Accessed 8 Oct. 2025.

[2] Haas, Mark. “Mesoamerican Nephropathy: Pathology in Search of Etiology.” Kidney International, vol. 93, no. 3, Mar. 2018, pp. 538–540, https://doi.org/10.1016/j.kint.2017.09.025. Accessed 7 Oct. 2025.

[3] Iván Landires, et al. “Exome Analysis PointsAPOE4Haplotype as Major Risk to Develop Mesoamerican Nephropathy.” MedRxiv (Cold Spring Harbor Laboratory), 23 Feb. 2024, https://doi.org/10.1101/2024.02.22.24303190. Accessed 9 Oct. 2025.

[4] Marín-Medina, Alejandro, et al. “Genetic Factors Related to the Development or Progression of Mesoamerican Endemic Nephropathy.” International Journal of Molecular Sciences, vol. 26, no. 10, Aug. 2025, p. 4486, pubmed.ncbi.nlm.nih.gov/40429630/, https://doi.org/10.3390/ijms26104486. Accessed 8 Oct. 2025.

[5] Petropoulos, Zoe E., et al. “Climate Trends at a Hotspot of Chronic Kidney Disease of Unknown Causes in Nicaragua, 1973–2014.” International Journal of Environmental Research and Public Health, vol. 18, no. 10, 1 Jan. 2021, p. 5418, www.mdpi.com/1660-4601/18/10/5418, https://doi.org/10.3390/ijerph18105418. Accessed 6 Oct. 2025.

[6] Sanchez Polo, Vicente, et al. “Mesoamerican Nephropathy (MeN): What We Know so Far.” International Journal of Nephrology and Renovascular Disease, vol. 13, 22 Oct. 2020, pp. 261–272, www.ncbi.nlm.nih.gov/pmc/articles/PMC7588276/, https://doi.org/10.2147/IJNRD.S270709. Accessed 7 Oct. 2025.

[7] Valdivia Mazeyra, Mariel Fabiola, et al. “Mesoamerican Nephropathy: A Not so Unknown Chronic Kidney Disease.” Nefrología (English Edition), vol. 41, no. 6, 1 Nov. 2021, pp. 612–619, www.sciencedirect.com/science/article/pii/S201325142100136X#bib0025, https://doi.org/10.1016/j.nefroe.2021.12.009. Accessed 9 Oct. 2025.