Background:Growing evidence indicates that arsenic metabolism is associated with cardiometabolic outcomes but few studies have investigated the association of arsenic metabolism with blood pressure outcomes. Methods:We evaluated cross-sectional associations between urinary arsenic metabolites and blood pressure outcomes-systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure-among 393 participants in the MesoAmerican Nephropathy Occupational Study (MANOS) in El Salvador and Nicaragua. We applied three modeling approaches: (1) conventional models assessing each urinary arsenic species [inorganic arsenic (InAs), monomethylated arsenic (MMA), and dimethylated arsenic (DMA)] individually as a percentage of the sum of inorganic and methylated arsenic; (2) leave-one-out models evaluating the relative effects of two species while holding the third constant; and (3) principal components analysis (PCA) representing methylation steps of arsenic metabolism. Results:In conventional models adjusted for age, body mass index, worksite, pesticide use, smoking status, and water consumption, participants with higher vs. lower DMA% (>77.51% vs. ≤71.28% DMA over the sum of inorganic and methylated arsenic species) showed higher systolic blood pressure (β = 3.75 mmHg; 95% CI: 0.65, 6.85) and pulse pressure (β = 2.57 mmHg; 95% CI: 0.04, 5.10), while participants with higher vs. lower MMA% (>16.07% vs. ≤12.39%) showed lower systolic blood pressure (β = -3.70 mmHg; 95% CI: -6.86, -0.55) and pulse pressure (β = -2.76 mmHg; 95% CI: -5.33, -0.19). In leave-one-out models, higher DMA% (>77.51% vs. <71.28%) as a result of lower MMA%, was associated with higher systolic blood pressure (β = 7.24 mmHg; 95% CI: 2.25, 12.2), pulse pressure (β = 5.29 mmHg; 95% CI: 1.22, 9.36), and mean arterial pressure (β = 3.71 mmHg; 95% CI: -0.08, 7.50). PCA results supported these findings. The second methylation step from MMA to DMA was associated with higher systolic blood pressure (β = 0.93 mmHg; 95% CI: 0.11, 1.75) and pulse pressure (β = 0.74 mmHg; 95% CI: 0.07, 1.40). Conclusions:Our findings suggest that biomarkers of efficient methylation of inorganic arsenic to DMA are associated with higher blood pressure compared to partial methylation to MMA, highlighting the importance of arsenic metabolism profiles in cardiovascular risk assessment.

BACKGROUND:Mesoamerican nephropathy is a public health crisis in young men in Central America. The disease does not share risk factors of chronic kidney disease (i.e. diabetes and hypertension) commonly seen in the U.S. Exposure to nephrotoxic agrochemicals is a hypothesized contributor to disease, but individual-level exposure measurements are lacking, as are analyses of exposures and outcomes. OBJECTIVES:Measure associations between urinary pesticides and kidney function within the Mesoamerican Nephropathy Occupational Study, a cohort of male workers aged 18-45 in Nicaragua and El Salvador. METHODS:Urine from 285 participants at two timepoints, enrollment and one year later, was analyzed for glyphosate and AMPA using HPLC-MS/MS. Urine of 50 participants from enrollment was also analyzed for four organophosphate, two phenoxy acid, and five pyrethroid pesticide metabolites using HPLC-MS/MS. We estimated associations between urinary pesticides and agrochemical jobs and estimated glomerular filtration rate (eGFR) cross-sectionally, over one year, and over the study period (two-and-a-half years in Nicaragua; three years in El Salvador). RESULTS:Higher urine glyphosate levels were associated with lower eGFR over one year, with significant associations for the lower exposure group (≤median): -4.0 mL/min/1.73 m2 (95% CI: -7.2, -0.87 mL/min/1.73 m2). However, participants with detectable urine glyphosate at both time points had lower odds of at least a 10% decline in eGFR decline over the study period (OR 0.33; 95% CI: 0.16, 0.65). The protective effect in our longer-term model may reflect healthy worker bias. Meanwhile, having an agrochemical job was significantly associated with higher odds of at least a 20% decline in eGFR over the study period (OR 1.7; 95% CI: 1.3, 2.3). SIGNIFICANCE:Urine pesticide levels were not consistently associated with reduced kidney function. 59 Having an agrochemical job was a predictor of kidney function decline. Other agricultural exposures, either individually or in combination with pesticides, may drive disease risks observed in this population. IMPACT:We evaluated urine concentrations of pesticides, including glyphosate, in a cohort of male workers in five industries (brickmaking, road construction, corn, plantain, and sugarcane) in El Salvador and Nicaragua, an area with endemic Mesoamerican nephropathy and where pesticide biomonitoring data in general is lacking. We found weak and limited evidence of associations between urinary glyphosate or other pesticide levels and change in kidney function. However, we observed a significant positive association between having an agrochemical job and kidney decline over the study period.

Exposure to elements such as arsenic, cadmium, lead, and mercury, which are associated with cancer, cardiovascular disease, and kidney disease, are not well-studied in Central American populations. We evaluated differences in urine metal(loid) concentrations by dietary/behavioral, occupational, and geographic factors within a cohort of adult male workers in El Salvador in the MesoAmerican Nephropathy Occupational Study (MANOS). We measured spot urinary concentrations of 14 metal(loid)s and speciated arsenic in 194 participants in 2021. We compared concentrations in our study to the US National Health and Nutrition Examination Survey (NHANES) data. We used multiple linear regression to examine known metal(loid) exposure sources (e.g. smoking and seafood consumption) and the role of occupational and geographic-related predictors (e.g. industry and region) in association with urinary metal(loid) concentrations. We detected 13 of 14 metal(loid)s and all targeted biomarkers of arsenic species in participants' urine samples, with detection frequencies ranging from 4-100%. Compared to NHANES data, MANOS participants had significantly higher (p<0.05) median concentrations (& micro;g/L) of all arsenic species (sum of inorganic arsenic species 10 vs. 54), cobalt (0.39 vs. 0.030), and thallium (0.27 vs. 0.20), while molybdenum and uranium were significantly lower in MANOS (35 vs. 49 and 0.0035 vs. 0.75, respectively). Arsenobetaine concentrations were 140% higher (95% CI: 58, 260%) in recent seafood consumers. Among smokers, cadmium and lead were 57% (95% CI: 21, 102) and 38% higher (95% CI: 3, 85), respectively. The sum of inorganic arsenic species was 48% higher (95% CI: 24, 77), while mercury and lead were-30% (95% CI:-48,-6.4) and-43% (95% CI:-59,-22) lower in sugarcane workers compared to corn workers. Compared to participants with normal kidney function, indicated by estimated glomerular filtration rate (eGFR) >90 ml/min/1.73m(2), participants with higher Ba, Cs, Pb, and Tl concentrations had lower kidney function, while those with higher Mn and U had higher kidney function. Findings suggest dietary, renal, and workplace factors influence some metal(loid) exposures in El Salvador. Understanding sources of metal(loid) concentrations may help identify strategies to reduce exposures and accompanying health risks.

BACKGROUND:Chronic kidney disease of unknown etiology (CKDu) is a major health concern among outdoor manual workers in rural Central America and South Asia. The CURE study is a prospective longitudinal cohort designed to investigate CKDu's environmental risk factors through standardized exposure assessments, questionnaires, and biological and environmental sample collection. METHODS:This manuscript details the development of a standardized exposure assessment protocol within the CKDu CURE Consortium. The study recruits adults (18-45 years) from CKDu hotspots across five countries, ensuring proportional representation across three eGFR categories (20-59, 60-89, ≥90 mL/min/1.73m2) and excluding participants with diabetes or other known CKD causes. The CURE study is committed to promptly returning clinically and environmentally relevant test results to participants after analysis. RESULTS:Exposure assessment includes demographics, healthcare access, nephrotoxic medications, infectious pathogens, and agricultural work conditions (e.g., heat stress, hydration, diet, agrochemicals, toxicants). Biological and environmental samples (water, dust, soil, wristbands) are collected considering seasonal variations. Omics analyses, including metabolomics, will investigate environmental and biological interactions. Statistical analyses will assess relationships between exposures and CKDu onset or progression, incorporating environmental mixture analyses. CONCLUSION:CURE will provide critical insights into CKDu risk factors, supporting future research and prevention strategies. A comprehensive exposure assessment will enhance understanding of environmental contributors, guiding interventions at individual, workplace, and community levels to mitigate CKDu's impact.

Introduction:There has been an alarming increase in the incidence of a chronic kidney disease (CKD) of unknown etiology primarily affecting young individuals engaged in agricultural activities in Mesoamerica and South Asia. Despite extensive research over the past 2 decades, causes remain unclear. The disease is characterized by progressive loss of kidney function with the absence of heavy proteinuria and hematuria. The International Prospective Study of CKD of Unknown Etiology in Agricultural Communities (CURE study) aims to do the following: (i) identify factors associated with kidney function decline among individuals with or at risk for CKD of uncertain etiology (CKDu); (ii) better characterize the clinical phenotypes of individuals with CKDu and differentiate them from other forms of CKD; (iii) employ advanced laboratory and data analysis methods to conduct discovery science related to risk factors, biomarkers, and causal mechanisms; and (iv) establish a biorepository for future research. Methods:The CURE study is a prospective cohort study of up to 3600 participants from 7 sites in Central America and India aged 18 to 45 years with estimated glomerular filtration rate (eGFR) ≥ 20 ml/min per 1.73 m2, no evidence of diabetes, and no other known causes of CKD. Biological samples and questionnaire data are collected from participants during 4 visits at 8-month intervals. Results:Blood, urine, and hair will be analyzed for kidney function biomarkers, trace elements, pesticides and other contaminants, untargeted metabolomics, and genetic assays. Environmental samples, collected from a subset of study participants, will be analyzed for trace elements, agrochemicals, and burning exposures. Conclusion:This study will provide novel information about CKDu etiology and clinical phenotypes across distinct geographies.

Introduction: Chronic kidney disease (CKD) of unknown etiology is a leading cause of mortality among young men in Nicaragua and El Salvador, but longitudinal trends in kidney health and disease incidence remain poorly characterized. Methods: We estimated glomerular filtration rate (eGFR) among young adult male workers in Nicaragua and El Salvador without known CKD (n = 569), aged 18 to 45 years, with follow-up every 6 months for 3 years. We estimated cumulative incidence of CKD, defined as ≥ 2 eGFR measurements < 60 ml/min per 1.73 m2, and incidence rate in person-years. We used a hierarchical clustering approach to identify latent patterns in longitudinal eGFR. Results: Cumulative incidence was 4.5% (n = 24). Incidence rate was 22.2 cases per 1000 person-yrs (95% confidence interval [CI]: 13.6–30.9). All incident cases experienced eGFR decline > 5 ml/min per 1.73 m2/yr. Mean annual decline in eGFR was −4.3 ml/min per 1.73 m2/yr (SEM: 0.3). Cluster analyses revealed 4 eGFR trajectories described as declining, stable and high, rapidly declining, and low and declining. Participants in the low and declining cluster (n = 57; 10.9%) experienced mean annual eGFR decline of −8.2 ml/min per 1.73 m2/yr (SD: 0.7), with a pattern suggesting seasonal kidney stress and recovery. Participants in the rapidly declining cluster (n = 10) were very young men (mean age: 23 yrs) who experienced a precipitous decrease in eGFR (mean annual decline: −12.5 ml/min per 1.73 m2/yr (SD: 1.6)). Conclusion: In this prospective cohort, we observed declining eGFR, including rapid decline in a young and apparently healthy subgroup. Relying on incidence measures alone may underestimate poor kidney health in the context of CKD of unknown etiology.

Silica nanoparticles found in sugarcane ash have been postulated to be a toxicant contributing to chronic kidney disease (CKD) of unknown etiology. However, although the administration of manufactured silica nanoparticles is known to cause chronic tubulointerstitial disease in rats, the effect of administering sugarcane ash on kidney pathology remains unknown. Here, we investigated whether sugarcane ash can induce CKD in rats. Sugarcane ash was administered for 13 wk into the nares of rats (5 mg/day for 5 days/wk), and blood, urine, and kidney tissues were collected at 13 wk (at the end of ash administration) and in a separate group of rats at 24 wk (11 wk after ash administration was stopped). Kidney histology was evaluated, and inflammation and fibrosis (collagen deposition) were measured. Sugarcane ash exposure led to the accumulation of silica in the kidneys, lungs, liver, and spleen of rats. Mild proteinuria developed, although renal function was largely maintained. However, biopsies showed focal glomeruli with segmental glomerulosclerosis as well as tubulointerstitial inflammation and fibrosis that tended to worsen even after the ash administration had been stopped. Staining for the lysosomal marker lysosomal associated membrane protein-1 showed decreased staining in ash-administered rats consistent with lysosomal activation. In conclusion, sugarcane ash containing silica nanoparticles can cause CKD in rats. NEW & NEWSWORTHY Epidemics of chronic kidney disease of unknown etiology have been reported in many areas of the world. In Central America, it occurs most commonly in sugarcane workers. Although heat stress is a major risk factor, there is some evidence that there may be a toxin. Here we show that sugarcane ash containing silica nanoparticles can induce chronic kidney disease in rats with similar features as observed in humans.

Background There is growing attention on occupational heat stress in Central America, as workers in this region are affected by a unique form of chronic kidney disease. Previous studies have examined wet bulb globe temperatures and estimated metabolic rates to assess heat stress, but there are limited data characterizing heat strain among these workers. Objective The aims were to characterize heat stress and heat strain and examine whether job task, break duration, hydration practices, and kidney function were associated with heat strain. Methods We used data from the MesoAmerican Nephropathy Occupational Study, a cohort of 569 outdoor workers in El Salvador and Nicaragua who underwent workplace exposure monitoring, including continuous measurement of core body temperature (T c ), heart rate (HR), physical activity, and wet bulb globe temperature (WBGT), over the course of three days in January 2018 - May 2018. Participants represented five industries: sugarcane, corn, plantain, brickmaking, and construction. Results Median WBGTs were relatively high (>27 °C) at most sites, particularly when work shifts spanned the afternoon hours (e.g., 29.2 °C among plantain workers). Sugarcane workers, especially cane cutters in both countries and Nicaraguan agrichemical applicators, had the highest estimated metabolic rates (medians: 299–318 kcal/hr). Most workers spent little time on break (<10% of the shift), as determined by physical activity data. Overall, sugarcane workers—particularly those in Nicaragua—experienced the highest T c and HR values. However, a few workers in other industries reached high T c (>39 °C) as well. Impaired kidney function (estimated glomerular filtration rate <90 mL/min/1.73 m 2 ) was associated with higher T c and HR values, even after adjustment. Significance This is the largest study to-date examining heat stress and strain among outdoor workers in Central America. Workers at sugar companies regularly experienced T c > 38°C (76.9% of monitored person-days at Nicaraguan companies; 46.5% at Salvadoran companies). Workers with impaired kidney function had higher measures of T c and HR. Impact statement This study examined levels of occupational heat stress and heat strain experienced among outdoor workers in five industries in El Salvador and Nicaragua. We characterized heat stress using wet bulb globe temperatures and estimated metabolic rate and heat strain using core body temperature and heart rate. Sugarcane workers, particularly cane cutters and Nicaraguan agrichemical applicators, performed more strenuous work and experienced greater levels of heat strain. Impaired kidney function was associated with higher heart rates and core body temperatures.

The absence of a chronic kidney disease (CKD) registry in Ecuador makes it difficult to assess the burden of disease, but there is an anticipated increase in the incidence of CKD along with increasing diabetes, hypertension and population age. From 2012, augmented funding for renal replacement therapy expanded dialysis clinics and patient coverage. We conducted 73 in-depth sociological interviews with healthcare providers in eight provinces and collected quantitative epidemiological data on patients with CKD diagnoses from six national-level databases between 2015 and 2018. Datasets show a total of 17,484 dialysis patients in 2018, or 567 patients per million population (pmp), with an annual cost exceeding 11% of Ecuador's public health budget. Each year, there were 139-162 pmp new dialysis patients, while doctors reported waiting lists. The number of patients on peritoneal dialysis was static; those on hemodialysis increased over time. Only 13 of 24 provinces were found to have dialysis services, and nephrologists were clustered in major cities, which limits access, delays medical attention, and adds a travel burden on patients. Prevention and screening programs are scarce, while hospitalization is an important reality for CKD patients. CKD is an emerging public health crisis that has increased dramatically over the last decade in Ecuador and is expected to continue, making coverage for all patients impossible and the current structure, unsustainable. A patient registry would help health policymakers and administrators estimate the demand and progression of patients with consideration for comorbidities, disease stage, requirements and costs, mortality and follow-up. This should be used to help identify where to focus prevention and improved treatment efforts. Organized monitoring of CKD patients would benefit from improvements in patient referral. Community-based education and prevention programs, the strengthening of primary healthcare capacity (including basic routine tests) and improved nephrology services are also urgently needed.

It has been suggested not to use acute kidney «da ño» or «injuria» for several reasons: (1) lack of tradition, (2) the term "injuria" is a merely cosmetic change since it continues to be defined by renal function and not by objective markers of damage, independent of renal function.Theoretically, it would be possible for there to be patients with acute renal function impairment [IRA (AKI 1-3) or FRA (AKI 3)] and acute kidney injury, but also patients with acute kidney injury but without IRA or FRA.b The acronym CAC does seem to be considered subliminally in the SLANH proposal.d Despite the enormous implantation of these terms, especially beyond nephrology, it was considered that the terms micro-or macro-were not adequate because it is not about the existence of a "small" or a "big" albumin.e It is possible that the nomenclature associated with transplantation, barely existing in the KDIGO initiative on nomenclature and with Anglo-Saxon terminology well established even in daily practice (eg borderline, DGF due to delayed graft function, etc.), deserves itself an initiative of the respective transplant societies.It should be assessed whether a translation would improve the understanding of the texts, expand or speed up the results of search engines, improve the exchange of information between the different actors in the world of transplantation or, on the contrary, it would be a "new learning" that it would displace an already integrated knowledge without additional input.

Background Mortality from chronic kidney disease of unknown etiology (CKDu) is extremely high along the Pacific coast of Central America, particularly among sugarcane workers. The Mesoamerican Nephropathy Occupational Study (MANOS) is a prospective cohort study of CKDu among agricultural and non-agricultural workers in El Salvador and Nicaragua. The objective of this manuscript is to describe the MANOS cohort recruitment, baseline data collection, and CKDu prevalence after two rounds. Methods Workers with no known diabetes, hypertension, or CKD were recruited from sugarcane, corn, plantain, brickmaking, and road construction industries ( n = 569). Investigators administered questionnaires, collected biological samples, and observed workers for three consecutive workdays at the worksite. Serum specimens were analyzed for kidney function parameters, and used to calculate estimated glomerular filtration rate (eGFR). At six months, serum was collected again prior to the work shift. CKD at baseline is defined as eGFR ≤ 60 ml/min/1.73m 2 at both timepoints. Age-standardized prevalence was calculated by industry, country, and demographic measures. Kidney function parameters were compared by CKD status. Results Prevalence of CKD at baseline was 7.4% ( n = 42). Age-standardized prevalence was highest in Salvadoran sugarcane (14.1%), followed by Salvadoran corn (11.6%), and Nicaraguan brickmaking (8.1%). Nicaraguan sugarcane had the lowest prevalence, likely due to kidney function screenings prior to employment. Conclusion Despite efforts to enroll participants without CKD, our identification of prevalent CKD among agricultural and non-agricultural workers in the MANOS cohort indicates notable kidney disease in the region, particularly among sugarcane workers.

Background: In Central America, the COVID-19 pandemic coexists with a devastating epidemic of chronic kidney disease of unknown origin. The consequences of these overlapping health crises remain largely unknown. Methods: We assessed vulnerability to and impact of the first wave of COVID-19 on participants in a cohort study of chronic kidney disease (CKD) in El Salvador (n = 229). Participants were contacted by phone during August and September 2020. We queried changes to employment, healthcare access, household income and food security due to the pandemic (from March 2020 until the time of the interview) and COVID-19-associated symptoms during that time. Findings: We reached 94% of the cohort (n = 215). Nearly 40% of participants reported an unexpected change in employment or work activities and 8.8% reported new unemployment due to the pandemic. Participants with CKD (n = 27) had higher odds of reporting new income insecurity, food insecurity, and reductions in medical care access due to the pandemic. COVID-19-associated symptoms (an approximation of disease) were reported in 7.0% (n = 15). Participants with CKD were more likely to report COVID-19-associated symptoms compared to those without CKD, although these differences were not statistically significant. Conclusions: Overall, participants with CKD suffered greater economic consequences as a result of the pandemic and may have experienced higher incidence of COVID-19 disease, although laboratory diagnostics would be required to draw this conclusion. Longitudinal analyses are required to comprehensively evaluate the implications of the pandemic for individuals with CKD in Central America.

Se ha sugerido no usar «da ño» o «injuria» renal aguda por varias razones: 1) ausencia de tradición, 2) el término AKI es un cambio meramente cosmético pues se sigue definiendo por la función renal y no por marcadores objetivos de da ño, independientes de la función.Teóricamente sería posible que hubiera pacientes con deterioro agudo de la función renal [IRA (AKI 1-3) o FRA (AKI 3)] y da ño renal agudo, pero también pacientes con da ño renal agudo pero sin IRA o FRA. a Al describir los grados (categorías, estadios) de la ERC debería evitarse la utilización del adjetivo «severa» y utilizar «grave».Severa es una traducción literal del «severe» inglés, pero en espa ñol la palabra «severa» no significa grave sino rigurosa.

In 2002, a report from El Salvador described a high incidence of chronic kidney disease (CKD) of unknown cause, mostly in young males from specific coastal areas. Similar situations were observed along the Pacific Ocean coastline of other Central American countries and southern Mexico (Mesoamerica). This new form of CKD has been denominated Mesoamerican endemic nephropathy (MeN). The typical presentation of MeN is a young male from an endemic area with a family history of CKD, low eGFR, high serum creatinine, low level of albuminuria, hypokalemia, hyperuricemia, and urine urate crystals. Kidney biopsy demonstrating tubulointerstitial nephritis remains the gold standard for diagnosis but is available only for a minority. Commonly proposed causes include thermal stress/dehydration and/or exposure to environmental pollutants. However, likely, a third factor, which could be genetic or epigenetic, could contribute to the cause and development of the disease, along with social determinants. Currently, preventive measures focus on minimizing workers exposure to thermal stress/dehydration. There are many research opportunities and priorities should include clinical trials to evaluate the efficacy and safety of the current treatment protocols, along with etiological and genetic studies, and the development of kidney disease data systems. Although there is scant and controversial literature with regard s  to the etiology, diagnosis and management of the disease, our aim is to provide the reader a vision of the disease based on our experience.

Chronic kidney disease of unknown origin, which is exacting a rising death toll globally, is related to heat exposure and dehydration and is a sentinel disease in the era of climate change. But we can learn from this epidemic and choose a wiser path forward.