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Background and Objectives: Obstructive sleep apnea (SA) is common in older men and a contributor to negative cognitive, psychiatric, and brain health outcomes. Little is known about SA in those who played contact sports and are at increased risk of neurodegenerative disease(s) and other neuropathologies associated with repetitive head impacts (RHI). In this study, we investigated the frequency of diagnosed and witnessed SA and its contribution to clinical symptoms and tau pathology using PET imaging among male former college and former professional American football players. Methods: The sample included 120 former National Football League (NFL) players, 60 former college players, and 60 asymptomatic men without exposure to RHI (i.e., controls). Diagnosed SA was self-reported, and all participants completed the Mayo Sleep Questionnaire (MSQ, informant version), the Epworth Sleepiness Scale (ESS), neuropsychological testing, and tau (flortaucipir) PET imaging. Associations between sleep indices (diagnosed SA, MSQ items, and the ESS) and derived neuropsychological factor scores, self-reported depression (Beck Depression Inventory-II [BDI-II]), informant-reported neurobehavioral dysregulation (Behavior Rating Inventory of Executive Function-Adult Version [BRIEF-A] Behavioral Regulation Index [BRI]), and tau PET uptake, were tested. Results: Approximately 36.7% of NFL players had diagnosed SA compared with 30% of the former college football players and 16.7% of the controls. Former NFL players and college football players also had higher ESS scores compared with the controls. Years of football play was not associated with any of the sleep metrics. Among the former NFL players, diagnosed SA was associated with worse Executive Function and Psychomotor Speed factor scores, greater BDI-II scores, and higher flortaucipir PET standard uptake value ratios, independent of age, race, body mass index, and APOE ε4 gene carrier status. Higher ESS scores correlated with higher BDI-II and BRIEF-A BRI scores. Continuous positive airway pressure use mitigated all of the abovementioned associations. Among the former college football players, witnessed apnea and higher ESS scores were associated with higher BRIEF-A BRI and BDI-II scores, respectively. No other associations were observed in this subgroup. Discussion: Former elite American football players are at risk of SA. Our findings suggest that SA might contribute to cognitive, neuropsychiatric, and tau outcomes in this population. Like all neurodegenerative diseases, this study emphasizes the multifactorial contributions to negative brain health outcomes and the importance of sleep for optimal brain health.
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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 (Tc), 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 Tc and HR values. However, a few workers in other industries reached high Tc (>39 °C) as well. Impaired kidney function (estimated glomerular filtration rate <90 mL/min/1.73 m2) was associated with higher Tc 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 Tc > 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 Tc 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.
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Exposição Ocupacional , Insuficiência Renal Crônica , Humanos , Nicarágua , El Salvador , Taxa de Filtração Glomerular , Resposta ao Choque Térmico , Temperatura AltaRESUMO
Metals are suspected contributors of autoimmune disease among indigenous Americans. However, the association between metals exposure and biomarkers of autoimmunity is under-studied. In Nicaragua, environmental exposure to metals is also largely unexamined with regard to autoimmunity. We analyzed pooled and stratified exposure and outcome data from Navajo (n = 68) and Nicaraguan (n = 47) men of similar age and health status in order to characterize urinary concentrations of metals, compare concentrations with the US National Health and Nutrition Examination Survey (NHANES) male population, and examine the associations with biomarkers of autoimmunity. Urine samples were analyzed for metals via inductively coupled plasma mass spectrometry (ICP-MS) at the US Centers for Disease Control and Prevention. Serum samples were examined for antinuclear antibodies (ANA) at 1:160 and 1:40 dilutions, using an indirect immunofluorescence assay and for specific autoantibodies using enzyme-linked immunosorbent assay (ELISA). Logistic regression analyses evaluated associations of urinary metals with autoimmune biomarkers, adjusted for group (Navajo or Nicaraguan), age, and seafood consumption. The Nicaraguan men had higher urinary metal concentrations compared with both NHANES and the Navajo for most metals; however, tin was highest among the Navajo, and uranium was much higher in both populations compared with NHANES. Upper tertile associations with ANA positivity at the 1:160 dilution were observed for barium, cesium, lead, strontium and tungsten.
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Autoimunidade , Inquéritos Nutricionais , Adulto , Biomarcadores , Exposição Ambiental , Humanos , Masculino , Pessoa de Meia-Idade , Nicarágua , Estados Unidos , Adulto JovemRESUMO
Background: An epidemic of CKD in Central America predominantly affects males working in certain industries, including sugarcane. Urinary tract infections are commonly diagnosed among men in Nicaragua, who often receive antibiotics and nonsteroidal anti-inflammatory drugs for urinary symptoms. Methods: We followed 251 male Nicaraguan sugarcane workers in seven job tasks over one harvest and measured urine dipstick parameters, kidney injury biomarkers, and eGFR. We administered a questionnaire about urinary symptoms, health-related behaviors, and medication history. We cultured urine in a subset of workers. Results: The study population was composed of factory workers (23%), cane cutters (20%), irrigators (20%), drivers (16%), agrichemical applicators (12%), seeders/reseeders (6%), and seed cutters (4%). The mean age of participants was 33.9 years, and mean employment duration was 10.1 years. Cane cutters reported higher proportions of urinary-related symptoms compared with agrichemical applicators, irrigators, and seeders/reseeders. Seed cutters were more likely to take antibiotics (22%), whereas drivers and seeders/reseeders were more likely to take pain medications (27% and 27%, respectively). Proteinuria was uncommon, whereas dipstick leukocyte esterase was relatively common, especially among cane cutters, seed cutters, and seeders/reseeders (33%, 22%, and 21% at late harvest, respectively). Dipstick leukocyte esterase at late harvest was associated with a 12.9 ml/min per 1.73 m2 (95% CI, -18.7 to -7.0) lower mean eGFR and 2.8 times (95% CI, 1.8 to 4.3) higher mean neutrophil gelatinase-associated lipocalin. In general, workers who reported urinary-related symptoms had higher mean kidney injury biomarker levels at late harvest. None of the workers had positive urine cultures, including those reporting urinary symptoms and/or with positive leukocyte esterase results. Amoxicillin, ibuprofen, and acetaminophen were the most commonly used medications. Conclusions: Job task is associated with urinary symptoms and dipstick leukocyte esterase. Urinary tract infection is misdiagnosed based on leukocyte esterase, which may be an important predictor of kidney outcomes.
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Saccharum , Adulto , Fazendeiros , Humanos , Rim , Testes de Função Renal , Masculino , AutorrelatoRESUMO
RATIONALE & OBJECTIVE: In Central America, there is a high prevalence of chronic kidney disease (CKD) of nontraditional etiology often observed among agricultural workers. Few studies have assessed CKD prevalence among workers in nonagricultural occupations, which was the objective of this investigation. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Male and female workers (n = 224) employed by artisanal brickmaking facilities in La Paz Centro, Nicaragua. PREDICTORS: Age, sex, education, smoking status, body mass index, alcohol consumption, water consumption, first-degree relative(s) with CKD, years worked, hours worked per week, job category, study visit (baseline and follow-up), and self-reported hypertension and diabetes. OUTCOMES: CKD defined as estimated glomerular filtration rate (eGFR) < 60mL/min/1.73m2 at 2 time points 4 months apart and CKD stage. ANALYTICAL APPROACH: A linear mixed-effects model with an unstructured covariance matrix was used to evaluate the association between demographics, occupational risk factors, and eGFR at baseline. The interaction between risk factors and time with change in eGFR was also evaluated. Multivariable logistic regression models were used to evaluate predictors of CKD. RESULTS: The CKD prevalence was 12.1% (n = 27), 100% of cases were male, 30% had stage 5 CKD (eGFR < 15mL/min/1.73m2), and 22% were younger than 35 years. Proportions of participants with eGFRs < 60mL/min/1.73m2 at baseline and follow-up were 13.8% and 15.2%, respectively. Linear regression analysis demonstrated significant predictors of lower kidney function at baseline including oven work, older age, lack of education, and having an immediate family member with CKD. Predictors of CKD identified using logistic regression analysis included oven work and lack of education. LIMITATIONS: Crude job classification measures, loss to follow-up, self-reported exposures. CONCLUSIONS: The prevalence of CKD is high in this population of brick workers, suggesting that the epidemic of CKD affecting Mesoamerica is not limited to agricultural workers. These results are consistent with the hypothesis that occupational heat exposure is a risk factor for kidney disease in this region.
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Indústria da Construção , Doenças Profissionais/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nicarágua/epidemiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Prevalência , Estudos Prospectivos , Insuficiência Renal Crônica/etiologia , Fatores de Risco , Adulto JovemRESUMO
RATIONALE & OBJECTIVE: Mesoamerican nephropathy (MeN), a form of chronic kidney disease (CKD) of unknown cause in Central America, affects young individuals working in physically strenuous occupations. Repeated episodes of work-related kidney injury may lead to CKD in this setting. We aimed to better understand the burden and natural history of acute kidney injury (AKI) in workers at risk for MeN. STUDY DESIGN: Cross-sectional study of active sugarcane workers, followed by prospective follow-up of individuals with AKI. SETTING & PARTICIPANTS: 326 sugarcane workers with normal preharvest serum creatinine (Scr) values and no history of CKD in an MeN hotspot in Nicaragua near the end of the harvest, and prospective follow-up of workers with AKI. PREDICTOR: AKI during the harvest, as defined by Scr level increase ≥ 0.3mg/dL over baseline to a level ≥ 1.3mg/dL. OUTCOMES: Kidney function trajectory and development of CKD over 12 months. ANALYTICAL APPROACH: Linear regression models were used to analyze the association between job category and kidney function. For workers with AKI, the effect of time on Scr level was evaluated using linear mixed effects. RESULTS: 34 of 326 participants were found to have AKI, with a median late-harvest Scr level of 1.64mg/dL in the AKI group. Workers without AKI had a median Scr level of 0.88mg/dL. AKI was more common among cane cutters compared with other field workers. Participants with AKI had variable degrees of kidney function recovery, with median 6- and 12-month Scr values of 1.25 and 1.27mg/dL, respectively (P < 0.001 for each follow-up value compared to late-harvest Scr). When we compared workers' kidney function before the AKI episode to their kidney function at last follow-up, 10 participants with AKI developed de novo estimated glomerular filtration rate < 60mL/min/1.73m2 and 11 had a >30% decrease in estimated glomerular filtration rate. LIMITATIONS: Follow-up limited to 1 year and some loss to follow-up in the prospective component of the study. Broad definition of AKI that includes both acute and subacute kidney injury. CONCLUSIONS: In a group of sugarcane workers with normal preharvest kidney function, newly decreased kidney function developing during the harvest season was common. Of those with kidney injury, nearly half had established CKD 12 months later.
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Injúria Renal Aguda/induzido quimicamente , Doenças Profissionais/etiologia , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/epidemiologia , Saccharum/efeitos adversos , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/fisiopatologia , Adulto , América Central/epidemiologia , Creatinina/sangue , Estudos Transversais , Bases de Dados Factuais , Progressão da Doença , Fazendeiros/estatística & dados numéricos , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Doenças Profissionais/fisiopatologia , Saúde Ocupacional , Prevalência , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Medição de RiscoRESUMO
BACKGROUND: Leptospirosis is postulated as a possible cause of Mesoamerican Nephropathy (MeN) in Central American workers. OBJECTIVES: Investigate job-specific Leptospira seroprevalence and its association with kidney disease biomarkers. METHODS: In 282 sugarcane workers, 47 sugarcane applicants and 160 workers in other industries, we measured anti-leptospiral antibodies, serum creatinine, and urinary injury biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and N-acetyl-D-glucosaminidase (NAG). RESULTS: Leptospira seroprevalence differed among job categories and was highest among sugarcane cutters (59%). Seropositive sugarcane workers had higher NGAL concentrations (relative mean: 1.28; 95% CI: 0.94-1.75) compared to those who were seronegative, with similar findings among field and non-field workers. CONCLUSIONS: Leptospira seroprevalence varied by job category. There was some indication that seropositivity was associated with elevated biomarker levels, but results were inconsistent. Additional studies may help establish whether Leptospira infection plays any role in MeN among Central American workers.
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Anticorpos Antibacterianos/sangue , Leptospira/imunologia , Leptospirose , Insuficiência Renal Crônica , Adulto , Biomarcadores/sangue , Creatinina/sangue , Fazendeiros/estatística & dados numéricos , Feminino , Humanos , Interleucina-18/sangue , Leptospirose/sangue , Leptospirose/complicações , Leptospirose/epidemiologia , Leptospirose/imunologia , Lipocalina-2/sangue , Masculino , Pessoa de Meia-Idade , Nicarágua/epidemiologia , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Estudos Soroepidemiológicos , Adulto JovemRESUMO
BACKGROUND: Mesoamerican nephropathy (MeN) is a kidney disease of unknown cause that mainly affects working-age men in Central America. Despite being a major cause of morbidity and mortality in this region, its clinical characteristics have not been well defined. STUDY DESIGN: Cross-sectional family-based study. SETTING & PARTICIPANTS: 266 members of 24 families with high chronic kidney disease (CKD) burdens in a MeN hotspot in Northwestern Nicaragua. We compared clinical and biochemical characteristics of affected individuals first with their unaffected relatives and then with NHANES (National Health and Nutrition Examination Survey) participants with CKD in order to reveal identifying features of MeN. PREDICTOR: CKD defined as serum creatinine level ≥ 1.5mg/dL in men and ≥1.4mg/dL in women. OUTCOMES: Clinical and biochemical parameters, including serum sodium, potassium, bicarbonate, calcium, magnesium, phosphorus, and uric acid. RESULTS: Hyperuricemia, in many cases severe, was common among patients with MeN. Uric acid levels in patients with MeN were higher than those in NHANES participants (mean, 9.6 vs 7.4mg/dL for men in each group) despite more frequent use of uric acid-lowering medications in Nicaraguan individuals (71.7% vs 11.2%). In multivariable linear mixed-effects regression analysis, uric acid levels were 2.0mg/dL (95% CI, 1.0-3.0; P<0.001) higher in patients with MeN compared with their NHANES counterparts after adjusting for age, estimated glomerular filtration rate, and uric acid-lowering therapies. In contrast to prior reports, hyponatremia and hypokalemia were not common. LIMITATIONS: CKD defined by single serum creatinine measurement; population likely not representative of full MeN phenotype spectrum across Central America; major differences between MeN and NHANES groups in important characteristics such as age, ancestry, and recruitment method. CONCLUSIONS: Hyperuricemia out of proportion to the degree of decreased kidney function was common among Nicaraguan patients with MeN. Our results suggest that rather than being solely a consequence of CKD, hyperuricemia may play a role in MeN pathogenesis, a hypothesis that deserves further study.
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Insuficiência Renal/diagnóstico , Insuficiência Renal/epidemiologia , Adulto , Idoso , América Central/epidemiologia , Estudos Transversais , Feminino , Humanos , Hiperuricemia/etiologia , Masculino , Pessoa de Meia-Idade , Nicarágua/epidemiologia , Inquéritos Nutricionais , Insuficiência Renal/complicaçõesRESUMO
BACKGROUND: In Central America, an epidemic of chronic kidney disease of unknown cause disproportionately affects young male agricultural workers. STUDY DESIGN: Longitudinal cohort study. SETTING & PARTICIPANTS: 284 sugarcane workers in 7 jobs were recruited from one company in northwestern Nicaragua. Blood and urine samples were collected before and near the end of the 6-month harvest season. PREDICTORS: Job category (cane cutter, seeder, seed cutter, agrichemical applicator, irrigator, driver, and factory worker); self-reported water and electrolyte solution intake. OUTCOMES & MEASUREMENTS: Changes in levels of urinary kidney injury biomarkers normalized to urine creatinine level, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), N-acetyl-ß-d-glucosaminidase (NAG), and albumin; serum creatinine-based estimated glomerular filtration rate (eGFR). RESULTS: Mean eGFR was 113 mL/min/1.73 m(2) and <5% of workers had albuminuria. Field workers had increases in NGAL and IL-18 levels that were 1.49 (95% CI, 1.06 to 2.09) and 1.61 (95% CI, 1.12 to 2.31) times as high, respectively, as in non-field workers. Cane cutters and irrigators had the greatest increases in NGAL levels during the harvest, whereas cane cutters and seeders had the greatest increases in IL-18 levels. Electrolyte solution consumption was associated with lower mean NGAL and NAG levels among cane cutters and lower mean IL-18 and NAG levels among seed cutters; however, there was no overall effect of hydration among all workers. On average, workers with the largest increases in NGAL and NAG levels during the harvest had declines in eGFRs of 4.6 (95% CI, 1.0 to 8.2) and 3.1 (95% CI, -0.6 to 6.7) mL/min/1.73 m(2), respectively. LIMITATIONS: Surrogate exposure measure, loss to follow-up. CONCLUSIONS: Results are consistent with the hypothesis that occupational heat stress and volume depletion may be associated with the development of kidney disease, and future studies should directly measure these occupational factors. The presence of urine tubular injury markers supports a tubulointerstitial disease that could occur with repeated tubular injury.
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Fazendeiros , Exposição Ocupacional/efeitos adversos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/urina , Saccharum , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Coortes , Desidratação/sangue , Desidratação/epidemiologia , Desidratação/urina , Feminino , Resposta ao Choque Térmico/fisiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Nicarágua/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Adulto JovemRESUMO
BACKGROUND: An epidemic of chronic kidney disease (CKD) of non-traditional aetiology has been recently recognized by health authorities as a public health priority in Central America. Previous studies have identified strenuous manual work, agricultural activities and residence at low altitude as potential risk factors; however, the aetiology remains unknown. Because individuals are frequently diagnosed with CKD in early adulthood, we measured biomarkers of kidney injury among adolescents in different regions of Nicaragua to assess whether kidney damage might be initiated during childhood. METHODS: Participants include 200 adolescents aged 12-18 years with no prior work history from four different schools in Nicaragua. The location of the school served as a proxy for environmental exposures and geographic locations were selected to represent a range of factors that have been associated with CKD in adults (e.g. altitude, primary industry and CKD mortality rates). Questionnaires, urine dipsticks and kidney injury biomarkers [interleukin-18, N-acetyl-d-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL) and albumin-creatinine ratio] were assessed. Biomarker concentrations were compared by school using linear regression models. RESULTS: Protein (3.5%) and glucose (1%) in urine measured by dipstick were rare and did not differ by school. Urine biomarkers of tubular kidney damage, particularly NGAL and NAG, showed higher concentrations in those schools and regions within Nicaragua that were defined a priori as having increased CKD risk. Painful urination was a frequent self-reported symptom. CONCLUSIONS: Although interpretation of these urine biomarkers is limited because of the lack of population reference values, results suggest the possibility of early kidney damage prior to occupational exposures in these adolescents.
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Biomarcadores/urina , Insuficiência Renal Crônica/urina , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Nicarágua/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: There is an epidemic of chronic kidney disease (CKD) of unknown etiology in Central American workers. OBJECTIVES: To investigate changes and job-specific differences in kidney function over a 6-month sugarcane harvest season, explore the potential role of hydration, and measure proteinuria. METHODS: We recruited 284 Nicaraguan sugarcane workers performing seven distinct tasks. We measured urine albumin and serum creatinine and estimated glomerular filtration rate (eGFR). RESULTS: eGFR varied by job and decreased during the harvest in seed cutters (-8·6 ml/min/1·73 m(2)), irrigators (-7·4 ml/min/1·73 m(2)), and cane cutters (-5·0 ml/min/1·73 m(2)), as compared to factory workers. The number of years employed at the company was negatively associated with eGFR. Fewer than 5% of workers had albumin-to-creatinine ratio (ACR) >30 mg/g. CONCLUSIONS: The decline in kidney function during the harvest and the differences by job category and employment duration provide evidence that one or more risk factors of CKD are occupational.
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Fazendeiros , Nefropatias/epidemiologia , Doenças Profissionais/epidemiologia , Proteinúria/epidemiologia , Saccharum , Adolescente , Adulto , Albuminúria , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/sangue , Nefropatias/fisiopatologia , Nefropatias/urina , Masculino , Pessoa de Meia-Idade , Nicarágua/epidemiologia , Doenças Profissionais/sangue , Doenças Profissionais/fisiopatologia , Doenças Profissionais/urina , Proteinúria/sangue , Proteinúria/fisiopatologia , Proteinúria/urina , Adulto JovemRESUMO
Recent reports have described an apparent epidemic of CKD along the Pacific coast of Central America, such that CKD is a leading cause of death among working-age men in lower-altitude agricultural communities in this region. Given the limited availability of kidney replacement therapies in this region, CKD often is a terminal diagnosis, lending greater urgency to the identification of a modifiable cause. This article discusses the epidemiology of CKD in this region, reviews the clinical features of this CKD outbreak, discusses potential causes and the evidence supporting these hypotheses, and highlights the wider implications of this epidemic of CKD.