CKDu is often described as a silent health threat, and the description is apt. Unlike the chronic kidney disease familiar to nephrologists in high-income settings, CKDu progresses without the classic metabolic hallmarks such as obesity and diabetes. It is typically not diagnosed until it reaches an advanced stage, at which point it is often fatal. The disease has been documented primarily among young adult males engaged in heat-intensive manual labor in equatorial agricultural communities, with major hotspots in Central America and South Asia and additional clusters reported in rural agricultural regions from Africa to Thailand and even in Texas. Because the condition does not fit the standard metabolic profile of kidney disease, and because it clusters geographically in ways that defy a single explanation, its underlying causes remain poorly understood despite years of investigation. What has become increasingly clear is that the burden falls on working-age populations, robbing communities of people in the prime of life.

The new research emerged from a collaboration between Boston University School of Public Health and Nicaragua-based colleagues, who together analyzed survey and biospecimen data collected in 2023 from adolescents and young adults living in five regions of Nicaragua. The study area carries a high burden of CKDu, which in Nicaragua is also referred to as Mesoamerican Nephropathy. The researchers measured participants’ estimated glomerular filtration rate, the standard clinical indicator of how well the kidneys filter waste from the blood, and used it to distinguish between two distinct risk profiles. One profile reflected the non-metabolic characteristics associated with CKDu risk. The other reflected metabolic kidney disease risk, assessed through participants’ history of high body mass index, diabetes, and hypertension. The team also gathered data on employment, sociodemographic characteristics, and environmental exposures, allowing them to test which factors tracked with declining kidney function.

The results upended two assumptions at once. First, the prevalence of poor kidney health among young girls and women was greater than previously known. This population has often been excluded from CKDu research altogether, precisely because they are rarely diagnosed with the disease; screening programs have concentrated on men working in sugarcane production, so women and girls simply never entered the data. Second, the elevated risk observed among these young females was strongly associated with high body mass index levels, pointing toward metabolic kidney disease rather than the heat-driven, non-metabolic form that defines CKDu. In other words, the study appears to have captured early signals of a parallel epidemic of metabolic kidney dysfunction developing alongside the recognized occupational one, in a population that existing surveillance systems were never designed to detect.

The occupational story did not disappear entirely. The researchers did identify poor kidney health among heat-exposed young males working in sugarcane fields, consistent with the established understanding of CKDu as a disease linked to extreme occupational heat. Yet the majority of participants who exhibited higher poor kidney health did not work in heat-intensive environments at all. That single observation reframes the entire epidemiology of the region. Extreme heat, while clearly important, is not the sole driver of poor kidney health among young people there. Instead, the data suggest multiple pathways to kidney disease operating simultaneously, some occupational and some not, converging on a generation that is losing kidney function at younger ages than comparable populations in the United States, against whom the Nicaraguan participants were benchmarked.

Just as revealing were the factors that did not show up. The researchers did not observe significant links between poor kidney health and drinking water, low socioeconomic status, or non-sugarcane heat-intensive work. These null findings matter because several of them correspond to leading hypotheses in the CKDu literature. Contaminated or insufficient drinking water, poverty, and heat exposure in forms of manual labor other than sugarcane harvesting have all been proposed as contributors to the disease. The absence of significant associations in this dataset does not settle those debates, but it narrows the field and strengthens the case made by the study’s senior and corresponding author, Jessica Leibler, associate professor of environmental health at Boston University School of Public Health, that non-occupational factors such as genetic susceptibilities or environmental exposures may be shaping kidney health in the region from an early age.

For the research team, the surprise was intellectual but the implication is practical. “We were surprised to see that there appears to be multiple pathways to kidney disease in this region among young people and that exposure to extreme heat, while important, is not the sole driver of poor kidney health here,” Leibler says. “We were also interested to see how prevalent poor kidney health was among girls and young women. We believe we identified early and important signals of kidney disease risk that may allow for early interventions in this region.” Early intervention is the operative phrase. If kidney dysfunction is detectable in adolescents and young adults through estimated glomerular filtration rate measurements and metabolic indicators, then screening programs that currently begin, in effect, with adult male sugarcane workers are arriving decades and one entire demographic group too late.

Co-lead author Selene Vences Brown, a PhD student in environmental health at Boston University School of Public Health, draws the surveillance conclusion explicitly. “Our findings suggest that there may be non-occupational factors affecting kidney health in this region, such as genetic susceptibilities or environmental exposures, and that young people, including girls and women, should be involved in surveillance efforts,” she says. “To date, kidney disease screening is focused on men working in sugarcane production.” The consequences of that narrow focus extend well beyond clinic walls. Co-lead author Yirong Yuan, a PhD student in biostatistics at the school, emphasizes the social dimension: CKDu inflicts social and economic consequences, leading to financial instability for families and contributing to intergenerational poverty. A disease that strikes working-age adults in agricultural communities removes household earners, drains family savings, and passes economic disadvantage to the next generation, making early detection not only a medical priority but an economic one.

The team is not stopping at a cross-sectional snapshot. The researchers are continuing to study early-life, metabolic, and occupational risk factors among young people in Nicaragua, and Yuan is currently analyzing longitudinal kidney health data to identify patterns and trajectories in kidney function among these populations. Longitudinal analysis is the critical next step, because distinguishing a temporary dip in filtration rate from the beginning of a progressive, irreversible decline requires watching the same individuals over time. The work also stands as a model of research practice. Leibler describes it as a testament to cross-collaboration across research disciplines, with doctoral students in environmental health and biostatistics co-leading the manuscript, and says she would like to see that collaborative approach become more commonplace in doctoral studies because it reflects a sharing of expertise vital for impactful public health research. Vences Brown adds a note about the human foundation of the project: “We are very grateful to our Nicaragua-based colleagues, whose dedication and commitment to this research were critical to the project’s success.”

Taken together, the study delivers a message that reaches far beyond the sugarcane fields of Nicaragua. CKDu is a global problem, occurring across Central America and South Asia with additional hotspots in rural agricultural communities from Africa to Thailand and within the United States itself, and the Nicaraguan findings suggest that wherever it takes hold, the populations at risk may be broader and younger than screening programs assume. Adolescents and young women, historically invisible in CKDu research because they are rarely diagnosed, now appear in the data with measurable kidney dysfunction, some of it tied to metabolic risk factors such as elevated body mass index rather than to heat exposure at all. If the silent epidemic of kidney disease in hot agricultural regions is to be caught before it becomes fatal, the surveillance net will need to widen to include the young, the female, and the non-agricultural, and it will need to begin well before workers ever set foot in a cane field.

Subject of Research: Chronic kidney disease of unknown origin and metabolic kidney disease risk among adolescents and young adults in Nicaragua

Article Title: Kidney disease in Nicaragua linked to adolescents and young women, and those without occupational heat exposure

Article References: Kidney disease in Nicaragua linked to adolescents and young women, and those without occupational heat exposure. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: CKDu, chronic kidney disease, Nicaragua, Mesoamerican Nephropathy, kidney health, adolescents, young women, body mass index, occupational heat exposure, metabolic kidney disease, public health surveillance, Boston University

Arsenic is a naturally occurring metalloid found in groundwater, soil, and certain crops across much of the world, and chronic exposure is well established as a risk factor for cardiovascular disease, cancers, and skin lesions. Once absorbed, inorganic arsenic does not simply accumulate unchanged. The body metabolizes it in two successive methylation steps, enzymatically attaching methyl groups to convert inorganic arsenic into monomethylated arsenic, or MMA, and then into dimethylated arsenic, or DMA. These methylated forms are excreted in urine, and for decades the methylation process was considered detoxifying, since the fully dimethylated product is generally less reactive at the cellular level than its predecessors. But this conventional wisdom has been increasingly challenged by studies hinting that trivalent intermediates formed along the pathway may be more toxic than the parent compound itself.

The MANOS research team, led by Margaret Quaid of Boston University School of Public Health together with collaborators at institutions in the United States, El Salvador, and Nicaragua, set out to examine whether specific arsenic metabolism profiles were associated with blood pressure among working men in a region where both arsenic exposure and an unexplained kidney disease overlap. The study included 393 male participants drawn from the broader occupational cohort, and the researchers measured the concentrations of inorganic arsenic, MMA, and DMA in urine samples, expressing each species as a percentage of the total inorganic and methylated arsenic. Blood pressure outcomes included systolic pressure, diastolic pressure, pulse pressure, and mean arterial pressure, all adjusted for age, body mass index, worksite, pesticide use, smoking status, and water consumption.

The results revealed a pattern that at first glance seems counterintuitive. Participants with higher percentages of DMA, the end product of complete arsenic methylation, tended to have higher systolic blood pressure and wider pulse pressure. In the conventional models, each percentage point increase in DMA was associated with a 0.17 millimeter of mercury increase in systolic pressure and a 0.14 millimeter of mercury increase in pulse pressure. Conversely, participants with higher percentages of MMA, indicating incomplete methylation, showed lower systolic and pulse pressures, with each percentage point increase in MMA corresponding to a 0.37 and 0.31 millimeter of mercury decrease respectively. In other words, the men whose bodies pushed arsenic metabolism further along the detoxification pathway were the ones showing elevated cardiovascular readings, not those who stalled at an intermediate step.

Because the three urinary metabolite percentages are mathematically interdependent, the researchers took care to disentangle their individual contributions using two additional analytical strategies. In leave-one-out models, they evaluated the relative effect of two species while statistically holding the third constant. These models reinforced the initial findings: higher DMA at the expense of MMA was associated with increased systolic blood pressure, with an effect estimate of 0.33 millimeters of mercury per percentage point, and increased pulse pressure of 0.29 millimeters of mercury per percentage point. A third approach using principal components analysis, a statistical technique that compresses correlated variables into independent axes representing the two methylation steps, provided converging evidence. The component capturing the second methylation step, the conversion of MMA to DMA, was associated with a 0.93 millimeter of mercury increase in systolic pressure and a 0.74 millimeter of mercury increase in pulse pressure.

The consistency of the effect across three distinct modeling frameworks lends weight to the authors’ conclusion that efficient methylation of inorganic arsenic all the way to DMA is associated with higher blood pressure compared with partial methylation to MMA. This finding complicates the simplistic narrative of methylation as unambiguously protective. It aligns instead with a growing body of research suggesting that the methylation process may generate intermediate trivalent species, such as monomethylarsinous acid, which are highly reactive and can disrupt cellular signaling, endothelial function, and oxidative stress pathways. If the second methylation step is inefficient at clearing these intermediates, or if individuals who methylate rapidly accumulate different arsenic species in tissues, the downstream cardiovascular consequences could differ in ways that conventional toxicity rankings fail to capture.

The biological mechanisms linking arsenic metabolism to blood pressure remain under active investigation, but several plausible pathways have been proposed. Arsenic exposure has been associated with impaired nitric oxide signaling, increased oxidative stress, vascular inflammation, and alterations in arterial stiffness, all of which can elevate systolic pressure and widen pulse pressure, a marker of arterial aging. The methylation process itself consumes methyl groups supplied by S-adenosyl methionine, drawing on one-carbon metabolism, a biochemical network that also regulates homocysteine levels and DNA methylation. Variation in the arsenite methyltransferase gene, known as AS3MT, and in nutritional factors such as folate and B vitamins can shift an individual’s metabolic profile substantially, meaning that two people exposed to identical arsenic levels may carry very different internal arsenic species distributions. The MANOS findings suggest these individual differences are not mere biochemical trivia but may carry meaningful cardiovascular consequences.

The context of the study population adds an important dimension to the findings. MesoAmerican nephropathy, also referred to as chronic kidney disease of unknown etiology, is an epidemic affecting agricultural workers along the Pacific coast of Central America, and arsenic exposure has been proposed among the candidate causes, alongside heat stress, dehydration, and pesticide exposures. By focusing on working men in sugarcane communities in El Salvador and Nicaragua, the MANOS investigators examined arsenic metabolism in a real-world setting of intense occupational and environmental stressors, rather than in a general population survey. The cross-sectional design means the study captures a single moment in time and cannot establish whether arsenic metabolism patterns cause the blood pressure differences or reflect some underlying physiological state. The authors are careful to frame the results as an association, and reverse causation or residual confounding cannot be excluded, particularly in a workforce with high rates of kidney impairment that could alter arsenic excretion.

Nevertheless, the study carries practical implications for how researchers and clinicians think about arsenic risk. Most environmental health surveillance measures total urinary arsenic, treating exposure as a single number. The MANOS results argue that the speciation profile, meaning the relative proportions of inorganic arsenic, MMA, and DMA, conveys additional information about cardiovascular vulnerability that total exposure alone would miss. If future longitudinal studies confirm that the second methylation step is genuinely associated with elevated blood pressure, then arsenic metabolism biomarkers could become part of cardiovascular risk assessment in exposed populations, helping to identify individuals who, despite similar exposure levels, face different health trajectories. Such work would also sharpen the search for modifiable factors, such as nutrition and one-carbon metabolism support, that shape methylation capacity and might therefore mediate arsenic’s cardiovascular effects.

For now, the study stands as a reminder that the body’s handling of a poison can be as consequential as the poison itself. In the cane fields of Central America, where arsenic, kidney disease, and hypertension intersect in an unfolding public health crisis, understanding the chemistry of methylation may prove essential to protecting the hearts and kidneys of the people who live and labor there. The researchers emphasize the importance of arsenic metabolism profiles in cardiovascular risk assessment, and their findings open a clear path for follow-up studies that follow exposed workers over time, track their metabolic profiles, and test whether the blood pressure patterns observed here translate into hypertension, arterial disease, and cardiovascular events in the years ahead.

Subject of Research: The association between arsenic metabolism profiles and blood pressure in MesoAmerican agricultural workers

Article Title: The association of arsenic metabolism and blood pressure: a cross-sectional analysis in the MesoAmerican Nephropathy Occupational Study (MANOS)

Article References: Quaid, M., Rodgers, K., Velázquez, J. J. A., García-Trabanino, R., Jarquin, E., Lopez-Pilarte, D., Leibler, J., Brooks, D., Glabonjat, R. A., Navas-Acien, A., Argos, M., & Scammell, M. K. (2026). The association of arsenic metabolism and blood pressure: a cross-sectional analysis in the MesoAmerican Nephropathy Occupational Study (MANOS). Environmental Health. https://doi.org/10.1186/s12940-026-01333-4

Image Credits: AI Generated

DOI: 10.1186/s12940-026-01333-4

Keywords: arsenic, arsenic metabolism, blood pressure, methylation, MMA, DMA, hypertension, MesoAmerican nephropathy, El Salvador, Nicaragua, environmental health, cardiovascular risk