Population-level detection of early loss of kidney function: 7-year follow-up of a young adult cohort at risk of Mesoamerican nephropathy.

BACKGROUND: Mesoamerican nephropathy is a leading contributor to premature mortality in Central America. Efforts to identify the cause are hampered by difficulties in distinguishing associations with potential initiating factors from common exposures thought to exacerbate the progression of all forms of established chronic kidney disease (CKD). We explored evidence of disease onset or departure from the healthy estimated glomerular filtration rate distribution [departure from ∼eGFR(healthy)] in an at-risk population. METHODS: Two community-based cohorts (adults aged 18-30 years, n = 351 and 420) from 11 rural communities in Northwest Nicaragua were followed up over 7 and 3 years respectively. We examined associations with both (i) incident CKD and (ii) the time point of departure from ∼eGFR(healthy), using a hidden Markov model. RESULTS: CKD occurred in men only (male incidence rate: 0.7%/year). Fifty-three (out of 1878 visits, 2.7%) and 8 (out of 1067 visits, 0.8%) episodes of probable departure from ∼eGFR(healthy) occurred in men and women, respectively. Cumulative time in sugarcane work and symptoms of excess occupational sun exposure were associated with incident CKD. The same exposures were associated with probability of departure from ∼eGFR(healthy) in time-updated analyses along with measured and self-reported weight loss, nausea, vomiting and cramps, as well as non-steroidal anti-inflammatory drug use. CONCLUSIONS: CKD burden in this population is high and risk factors for established disease are occupational. Additionally, a syndrome suggesting an alternative exposure is associated with evidence of disease onset supporting a possible separate unknown initiating factor for which further investigation is needed. Interventions to reduce the impact of occupational risks should be pursued meanwhile.

Kidney disease characteristics, prevalence, and risk factors in León, Nicaragua: a population-based study.

BACKGROUND: CKD of unknown etiology (CKDu) disproportionately affects young people in Central America who lack traditional CKD risk factors (diabetes and hypertension) and has instead been variably linked to heat stress, occupational and environmental exposures, nephrotoxic medications, and/or genetic susceptibility. This study aimed to estimate the prevalence of CKD and identify risk factors for traditional CKD and CKDu in Nicaragua. METHODS: Surveys and assessment for CKD markers in urine and serum were performed in 15-59 year olds in households of the León municipality of Nicaragua. The survey included questions on demographics, health behaviors, occupation, and medical history. Participants with CKD were subdivided into traditional CKD and suspected CKDu based on history of diabetes, hypertension, or other specified conditions. A multinomial logistic regression model was used to identify factors associated with traditional CKD and suspected CKDu, compared to the non-CKD reference group. RESULTS: In 1795 study participants, CKD prevalence was 8.6%. Prevalence in males was twofold higher than females (12% vs 6%). Of those with CKD, 35% had suspected CKDu. Both traditional CKD and CKDu were associated with male sex and increasing age. Traditional CKD was associated with a family history of CKD, history of urinary tract infections, and lower socioeconomic status, while CKDu was associated with drinking well water and a lower body mass index. CONCLUSIONS: Both traditional CKD and CKDu are significant burdens in this region. Our study supports previous hypotheses of CKDu etiology and emphasizes the importance of CKD screening.

Environmental exposures in young adults with declining kidney function in a population at risk of Mesoamerican nephropathy.

OBJECTIVES: There is an epidemic of Mesoamerican nephropathy (MeN) in Central America, where sugarcane production is prominent. Numerous causes are proposed, but to date limited evidence supports any one hypothesis. A nested case-control study using biosamples from a rural, community-based follow-up study of 350 young adults from Northwest Nicaragua at risk of MeN was conducted with the aim of characterising the associations between urinary concentrations of metals, pesticides and mycotoxins from samples collected in the first 6 months and decline in kidney function over 2 years. METHODS: Urine samples collected at baseline (pre-sugarcane harvest) and the first 6 month follow-up (post-sugarcane harvest) visit were tested. Twelve metals and metalloids (aluminium, total arsenic, cadmium, chromium, cobalt, copper, lead, manganese, mercury, selenium, silicon and strontium) were analysed by inductively coupled plasma-mass spectrometry. Twelve pesticides or their metabolites (2,4-dichlorophenoxyacetic acid, 3-phenoxybenzoic acid, 4-fluoro-3-phenoxybenzoic acid, chloro-3,3,3-trifluoro-1-propen-1-yl-2,2-dimethylcyclopropanecarboxylic acid, cis/trans 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, ethylenethiourea, glyphosate, 4-chloro-2-methylphenoxy acetic acid, 3-hydroxy-pyrimetanil, 5-hydroxytiabendazole, hydroxy-tebuconazole and 3,5,6-trichloro-2-pyridinol) and two mycotoxins (ochratoxin A (OTA) and citrinin (CIT)) were analysed by liquid chromatography coupled-mass spectrometry. Differences in the creatinine-corrected urinary concentrations of the measured exposures between outcome groups (participants with stable vs declining kidney function) were examined. RESULTS: Elevated levels of aluminium and total arsenic as well as metabolites of several pesticides were detected across the population. No differences were identified between the declining and stable groups in the levels of metals or pesticides tested. OTA and CIT were below the limit of detection. CONCLUSIONS: The tested metals, metalloids, pesticides and mycotoxins were not associated with loss of kidney function in participants at-risk of MeN.

Prevalence and Risk Factors for CKD Among Brickmaking Workers in La Paz Centro, Nicaragua.

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.

Decline in Kidney Function among Apparently Healthy Young Adults at Risk of Mesoamerican Nephropathy.

Background Epidemic levels of CKD of undetermined cause, termed Mesoamerican nephropathy in Central America, have been found in low- and middle-income countries. We investigated the natural history of, and factors associated with, loss of kidney function in a population at high risk for this disease.Methods We conducted a 2-year prospective, longitudinal study with follow-up every 6 months in nine rural communities in northwestern Nicaragua and included all men (n=263) and a random sample of women (n=87) ages 18-30 years old without self-reported CKD, diabetes, or hypertension. We used growth mixture modeling to identify subgroups of eGFR trajectory and weighted multinomial logistic regression to examine associations with proposed risk factors.Results Among men, we identified three subpopulations of eGFR trajectory (mean baseline eGFR; mean eGFR change over follow-up): 81% remained stable (116 ml/min per 1.73 m2; -0.6 ml/min per 1.73 m2 per year), 9.5% experienced rapid decline despite normal baseline function (112 ml/min per 1.73 m2; -18.2 ml/min per 1.73 m2 per year), and 9.5% had baseline dysfunction (58 ml/min per 1.73 m2; -3.8 ml/min per 1.73 m2 per year). Among women: 96.6% remained stable (121 ml/min per 1.73 m2; -0.6 ml/min per 1.73 m2 per year), and 3.4% experienced rapid decline (132 ml/min per 1.73 m2; -14.6 ml/min per 1.73 m2 per year; n=3 women). Among men, outdoor and agricultural work and lack of shade availability during work breaks, reported at baseline, were associated with rapid decline.Conclusions Although Mesoamerican nephropathy is associated with agricultural work, other factors may also contribute to this disease.

Effect of informal employment on the relationship between psychosocial work risk factors and musculoskeletal pain in Central American workers.

INTRODUCTION: The constant increase on the psychosocial demands experienced at work seems to contribute to the increase in health problems such as musculoskeletal pain (MSP). This association may be especially important in low-income and middle-income countries, where there is a large proportion of informal workers among whom there is little research. We analysed the association between psychosocial work risk factors and MSP among formal and informal workers using the First Central American Survey of Working Conditions and Health. METHODS: This is a representative sample (n=12 024) of the economically active population of the six Spanish-speaking countries of Central America. Prevalence ratios (PR) and corresponding 95% CIs from Poisson regression models were used to estimate the association between psychosocial work risk factors and the MSP. RESULTS: Compared with formal workers, informal workers reported higher prevalence of MPS in the body regions analysed (ie, cervicodorsal, lumbosacral, upper extremities) and higher exposure to psychosocial work risk factors. However, on the whole, the associations between the exposure to psychosocial work risk factors and the prevalence of MSP were similar for both formal and informal workers. Only the association between exposure to high demands and MSP in the upper extremities was higher (p=0.012) among formal (PR=1.69, 95% CI 1.46 to 1.96) than among informal workers (PR=1.40; 95% CI 1.30 to 1.51). CONCLUSION: Exposure to adverse levels of psychosocial work risk factors is associated with higher prevalence of MPS among both formal and informal workers. However, the role of employment informality in this association is complex and requires further examination.

Renal Morphology, Clinical Findings, and Progression Rate in Mesoamerican Nephropathy.

BACKGROUND: Mesoamerican nephropathy (MeN) is a chronic kidney disease affecting rural inhabitants in Central America. We have previously described the renal morphology in 8 patients from El Salvador. To confirm the renal pathology, we have studied kidney biopsies from patients with MeN in Nicaragua. Follow-up urine and blood samples from both biopsy studies were collected to investigate the natural history. STUDY DESIGN: Case series. SETTINGS & PARTICIPANTS: In the kidney biopsy study, 19 male sugarcane workers in Nicaragua with suspected MeN were investigated with questionnaires, kidney biopsies, and blood and urine analysis. Inclusion criteria were age 20 to 65 years and plasma creatinine level of 1.13 to 2.49mg/dL or estimated glomerular filtration rate (eGFR) of 30 to 80mL/min/1.73m2. Exclusion criteria were proteinuria with protein excretion > 3g/24 h, uncontrolled hypertension, diabetes mellitus, or other known kidney disease. In the follow up-study, blood and urine from the kidney biopsy study in Nicaragua (n=18) and our previous biopsy study of MeN cases in El Salvador (n=7) were collected 1 to 1.5 and 2 to 2.5 years after biopsy, respectively. OUTCOMES: Renal morphology, clinical, and biochemical characteristics, change in eGFR per year. MEASUREMENTS: eGFR was calculated using the CKD-EPI creatinine (eGFRcr), cystatin C (eGFRcys), and creatinine-cystatin C (eGFRcr-cys) equations. RESULTS: In the kidney biopsy study, participants had a mean eGFRcr of 57 (range, 33-96) mL/min/1.73m2. 47% had low plasma sodium and 21% had low plasma potassium levels. 16 kidney biopsies were representative and showed glomerulosclerosis (mean, 38%), glomerular hypertrophy, and signs of chronic glomerular ischemia. Mild to moderate tubulointerstitial damage and mostly mild vascular changes were seen. In the follow up-study, median duration of follow-up was 13 (range, 13-27) months. Mean change in eGFRcr was -4.4±8.4 (range, -27.7 to 10.2) mL/min/1.73m2 per year. Most patients had stopped working with sugarcane cultivation. LIMITATIONS: 3 biopsy specimens had 4 or fewer glomeruli. CONCLUSIONS: This study confirms the renal morphology of MeN: chronic glomerular and tubulointerstitial damage with glomerulosclerosis and chronic glomerular ischemia. Follow-up data show that eGFRs, on average, deteriorated.

Rationale, description and baseline findings of a community-based prospective cohort study of kidney function amongst the young rural population of Northwest Nicaragua.

BACKGROUND: An epidemic of Mesoamerican Nephropathy (MeN) is killing thousands of agricultural workers along the Pacific coast of Central America, but the natural history and aetiology of the disease remain poorly understood. We have recently commenced a community-based longitudinal study to investigate Chronic Kidney Disease (CKD) in Nicaragua. Although logistically challenging, study designs of this type have the potential to provide important insights that other study designs cannot. In this paper we discuss the rationale for conducting this study and summarize the findings of the baseline visit. METHODS: The baseline visit of the community-based cohort study was conducted in 9 communities in the North Western Nicaragua in October and November 2014. All of the young men, and a random sample of young women (aged 18-30) without a pre-existing diagnosis of CKD were invited to participate. Glomerular filtration rate (eGFR) was estimated with CKD-EPI equation, along with clinical measurements, questionnaires, biological and environmental samples to evaluate participants' exposures to proposed risk factors for MeN. RESULTS: We identified 520 young adults (286 males and 234 females) in the 9 different communities. Of these, 16 males with self-reported CKD and 5 females with diagnoses of either diabetes or hypertension were excluded from the study population. All remaining 270 men and 90 women, selected at random, were then invited to participate in the study; 350 (97%) agreed to participate. At baseline, 29 (11%) men and 1 (1%) woman had an eGFR <90 mL/min/1.73 m2. CONCLUSION: Conducting a community based study of this type requires active the involvement of communities and commitment from local leaders. Furthermore, a research team with strong links to the area and broad understanding of the context of the problem being studied is essential. The key findings will arise from follow-up, but it is striking that 5% of males under aged 30 had to be excluded because of pre-existing kidney disease, and that despite doing so 11% of males had an eGFR <90 mL/min/1.73 m2 at baseline.

Universalidad del constructo del Maslach Burnout Inventory en un contexto latinoamericano / Universality of the construct Maslach Burnout Inventory in a Latin American context

Resumen El uso universal del Maslach Burnout Inventory (MBI), y sus versiones, ha creado un marco de inferencias polémicas sobre el cimiento anglosajón del MBI. El estudio analiza la universalidad del constructo de burnout del MBI en un contexto latinoamericano, examinando su validez, mediante análisis factorial exploratorio, confirmatorio y de fiabilidad. Un total de 505 docentes nicaragüenses participaron en el estudio. El 41% de los ítems no superaron las cargas factoriales. El mayor cuestionamiento acopia las inferencias de las dimensiones Despersonalización y Realización personal, apuntando a la probable falta de correspondencia cultural del constructo. El Agotamiento emocional resultó consistente y con la fiabilidad aceptable. El modelo del análisis factorial confirmatorio con el mejor ajuste mostró que el burnout puede ser interpretado como parte de una sola variable latente. Se concluyó que el constructo del MBI, tal como se plantea, no muestra suficiente peso para asumir su universalidad entre culturas heterogéneas. Las inconsistencias encontradas en la Despersonalización y la Realización personal dan indicios que se trata de un fenómeno específico ligado a contextos culturales determinados.

Abstract The universal use of the Maslach Burnout Inventory (MBI) and its versions has created a framework of controversial inferences about the MBI's Anglo-Saxon foundation. The study analyzes the universality of the MBI burnout construct in a Latin American context, examining its validity, through exploratory, confirmatory factor analysis plus reliability; 505 Nicaraguan teachers participated in the study; 41% of the items did not surpass the factorial loads. The major inquiring points out to the inferences of the Depersonalization and Emotional exhaustion was consistent and with acceptable reliability. The model of Confirmatory Factor Analysis with the best fit showed that burnout can be interpreted as part of a single latent variable. It was concluded that the MBI construct, as proposed, does not show enough weight to assume its universality among heterogeneous cultures. The inconsistencies found in Depersonalization and Personal Realization give indications that it is a specific phenomenon linked to particular cultural contexts.

Heat stress, hydration and uric acid: a cross-sectional study in workers of three occupations in a hotspot of Mesoamerican nephropathy in Nicaragua.

OBJECTIVES: To study Mesoamerican nephropathy (MeN) and its risk factors in three hot occupations. DESIGN: Cross-sectional. SETTING: Chinandega and León municipalities, a MeN hotspot on the Nicaraguan Pacific coast, January-February 2013. PARTICIPANTS: 194 male workers aged 17-39 years: 86 sugarcane cutters, 56 construction workers, 52 small-scale farmers. OUTCOME MEASURES: (1) Differences between the three occupational groups in prevalences/levels of socioeconomic, occupational, lifestyle and health risk factors for chronic kidney disease (CKD) and in biomarkers of kidney function and hydration; (2) differences in prevalences/levels of CKD risk factors between workers with reduced estimated glomerular filtration rate (eGFRCKD-EPI <80 mL/min/1.73 m2) and workers with normal kidney function (eGFRCKD-EPI ≥80 mL/min/1.73 m2). RESULTS: Sugarcane cutters were more exposed to heat and consumed more fluid on workdays and had less obesity, lower blood sugar, lower blood pressure and a better lipid profile. Reduced eGFR occurred in 16%, 9% and 2% of sugarcane cutters, construction workers and farmers, respectively (trend cane > construction > farming, p=0.003). Significant trends (cane > construction > farming) were also observed for high serum urea nitrogen (blood urea nitrogen (BUN) >20 mg/dL), high serum creatinine (SCr >1.2 mg/dL), low urinary pH (≤5.5) and high BUN/SCr ratio (>20) but not for high urinary specific gravity (≥1.030). Sugarcane cutters also more often had proteinuria and blood and leucocytes in the urine. Workers with eGFR <80 mL/min/1.73 m2 reported a higher intake of water and lower intake of sugary beverages. Serum uric acid levels related strongly and inversely to eGFR levels (adj ß -10.4 mL/min/1.73 m2, 95% CI -12.2 to -8.5, p<0.001). No associations were observed for other metabolic risk factors, pesticides, non-steroidal anti-inflammatory drugs or alcohol. Among cane cutters, consumption of electrolyte hydration solution appeared preventive (adj ß 8.1 mL/min/1.73 m2, p=0.09). CONCLUSIONS: Heat stress, dehydration and kidney dysfunction were most common among sugarcane cutters. Kidney dysfunction also occurred to a lesser extent among construction workers, but hardly at all among small-scale farmers. High serum uric acid was associated with reduced kidney function.

Kidney function in sugarcane cutters in Nicaragua--A longitudinal study of workers at risk of Mesoamerican nephropathy.

BACKGROUND: Chronic kidney disease is common among sugarcane workers in Central America. The main risk factor seems to be repeated high-intensity work in hot environments. Several cross-sectional studies have been performed but few longitudinal studies. OBJECTIVES: The aim of the study was to examine whether kidney function changes over a few months of work during the harvest period. METHODS: A group of male sugarcane cutters in Nicaragua (N=29, aged 17-38 years) was examined with renal biomarkers before and after shift on the first day at the start of harvest, on the sixth day during acclimatization, and then in mid-harvest 9 weeks later. A reference group (N=25, mainly office workers) was examined with the same biomarkers at start of harvest, and then at end of harvest 5 months later. RESULTS: The pre-shift renal function decreased significantly during 9 weeks of work in the cane cutters. Mean serum creatinine increased (20%), mean estimated glomerular filtration rate decreased (9%, 10mL/min), serum urea N (BUN) increased (41%), and mean urinary neutrophil gelatinase-associated lipocalin (NGAL) increased (four times). The cane cutters also developed cross-shift increases in these biomarkers, in particular serum creatinine and BUN, and in urinary uric acid. The longitudinal decrease in eGFR tended to be associated with the cross-shift increase in serum creatinine. CONCLUSIONS: There was a remarkable decrease of glomerular kidney function, after only 9 weeks of harvest. The cross-shift increase in serum creatinine may be caused by dehydration (pre-renal dysfunction), and when repeated on a daily basis this may cause permanently reduced GFR.

Heat Stress Nephropathy From Exercise-Induced Uric Acid Crystalluria: A Perspective on Mesoamerican Nephropathy.

Mesoamerican nephropathy (MeN), an epidemic in Central America, is a chronic kidney disease of unknown cause. In this article, we argue that MeN may be a uric acid disorder. Individuals at risk for developing the disease are primarily male workers exposed to heat stress and physical exertion that predisposes to recurrent water and volume depletion, often accompanied by urinary concentration and acidification. Uric acid is generated during heat stress, in part consequent to nucleotide release from muscles. We hypothesize that working in the sugarcane fields may result in cyclic uricosuria in which uric acid concentrations exceed solubility, leading to the formation of dihydrate urate crystals and local injury. Consistent with this hypothesis, we present pilot data documenting the common presence of urate crystals in the urine of sugarcane workers from El Salvador. High end-of-workday urinary uric acid concentrations were common in a pilot study, particularly if urine pH was corrected to 7. Hyperuricemia may induce glomerular hypertension, whereas the increased urinary uric acid may directly injure renal tubules. Thus, MeN may result from exercise and heat stress associated with dehydration-induced hyperuricemia and uricosuria. Increased hydration with water and salt, urinary alkalinization, reduction in sugary beverage intake, and inhibitors of uric acid synthesis should be tested for disease prevention.

Risk factors for reduced glomerular filtration rate in a Nicaraguan community affected by Mesoamerican nephropathy.

INTRODUCTION: Mesoamerican nephropathy, also known as chronic kidney disease of unknown etiology, is widespread in Pacific coastal Central America. The cause of the epidemic is unknown, but the disease may be linked to multiple factors, including diet as well as environmental and occupational exposures. As many as 50% of men in some communities have Mesoamerican nephropathy. OBJECTIVE: Describe prevalence of reduced glomerular filtration rate in a region of Nicaragua suspected to harbor high rates of Mesoamerican nephropathy; and investigate potential risk factors for such reduction associated with agricultural work (such as pesticide exposure and specific agricultural tasks associated with increased heat stress); sugar consumption; and traditional factors such as age, sex, diabetes, hypertension and nephrotoxic medication use. METHODS: This study uses a cross-sectional design with nested case-control analysis. Cases were individuals with estimated glomerular filtration rates of <60mL/min/1.73m2 and controls were individuals with those >90mL/min/1.73m2, estimated using serum creatinine. Data on nutrition, past medical history, medication and substance use, and agricultural behaviors and exposures were collected using medical questionnaires from June through August, 2012. Venous blood and urine samples were collected to assess hemoglobin A1c, and dipstick proteinuria, respectively; anthropometry and blood pressure measurements were made using standard techniques. Analyses were conducted using chi square, and univariate and multiple logistic regression. RESULTS: Of 424 individuals in the study, 151 had an occupational history in agriculture. Prevalence of glomerular filtration rate <60mL/min/1.73m2 was 9.8% among women and 41.9% among men (male to female ratio = 4.3, p<0.0001). Proteinuria =300 mg/dL was observed in <10% of participants with decreased glomerular filtration rate. Hemoglobin A1c and use of NSAIDs were not associated with decreased glomerular filtration rate. Although systolic and diastolic blood pressure was higher among participants with decreased glomerular filtration rate (p <0.001), hypertension was uncommon. Significant agricultural risk factors for reduced glomerular filtration rate included increased lifetime days cutting sugarcane during the dry season (OR 5.86, 95% CI 2.45-14.01), nondeliberate pesticide inhalation (OR 3.31, 95% CI 1.32-8.31), and sugarcane chewing (OR 3.24, 95% CI 1.39-7.58). CONCLUSIONS: Our findings demonstrate a high prevalence of chronic kidney disease not linked to traditional risk factors, and suggest it may be associated instead with occupational exposure to heat stress in conjunction with pesticide inhalation, sugarcane chewing and sugar intake during the workday.

Fructokinase activity mediates dehydration-induced renal injury.

The epidemic of chronic kidney disease in Nicaragua (Mesoamerican nephropathy) has been linked with recurrent dehydration. Here we tested whether recurrent dehydration may cause renal injury by activation of the polyol pathway, resulting in the generation of endogenous fructose in the kidney that might subsequently induce renal injury via metabolism by fructokinase. Wild-type and fructokinase-deficient mice were subjected to recurrent heat-induced dehydration. One group of each genotype was provided water throughout the day and the other group was hydrated at night, after the dehydration. Both groups received the same total hydration in 24 h. Wild-type mice that received delayed hydration developed renal injury, with elevated serum creatinine, increased urinary NGAL, proximal tubular injury, and renal inflammation and fibrosis. This was associated with activation of the polyol pathway, with increased renal cortical sorbitol and fructose levels. Fructokinase-knockout mice with delayed hydration were protected from renal injury. Thus, recurrent dehydration can induce renal injury via a fructokinase-dependent mechanism, likely from the generation of endogenous fructose via the polyol pathway. Access to sufficient water during the dehydration period can protect mice from developing renal injury. These studies provide a potential mechanism for Mesoamerican nephropathy.

Prevalence of obesity, tobacco use, and alcohol consumption by socioeconomic status among six communities in Nicaragua.

OBJECTIVE: To describe the prevalence of noncommunicable disease (NCD) risk factors (overweight/obesity, tobacco smoking, and alcohol consumption) and identify correlations between these and sociodemographic characteristics in western and central Nicaragua. METHODS: This was a cross-sectional study of 1 355 participants from six communities in Nicaragua conducted in September 2007-July 2009. Demographic and NCD risk-related health behavior information was collected from each individual, and their body mass index (BMI), blood pressure, diabetes status, and renal function were assessed. Data were analyzed using descriptive statistics, bivariate analyses, and (non-stratified and stratified) logistic regression models. RESULTS: Of the 1 355 study participants, 22.0% were obese and 55.1% were overweight/obese. Female sex, higher income, and increasing age were significantly associated with obesity. Among men, lifelong urban living correlated with obesity (Odds Ratio [OR] = 4.39, 1.18-16.31). Of the total participants, 31.3% reported ever smoking tobacco and 47.7% reported ever drinking alcohol. Both tobacco smoking and alcohol consumption were strikingly more common among men (OR = 13.0, 8.8-19.3 and 15.6, 10.7-22.6, respectively) and lifelong urban residents (OR = 2.42, 1.31-4.47 and 4.10, 2.33-7.21, respectively). CONCLUSIONS: There was a high prevalence of obesity/overweight across all income levels. Women were much more likely to be obese, but men had higher rates of tobacco and alcohol use. The rising prevalence of NCD risk factors among even the poorest subjects suggests that an epidemiologic transition in underway in western and central Nicaragua whereby NCD prevalence is shifting to all segments of society. Raising awareness that health clinics can be used for chronic conditions needs to be priority.

Prevalence of obesity, tobacco use, and alcohol consumption by socioeconomic status among six communities in Nicaragua / Prevalencia de la obesidad, el tabaquismo y el consumo de alcohol según la condición socioeconómica en seis comunidades de Nicaragua

Objective. To describe the prevalence of noncommunicable disease (NCD) risk factors(overweight/obesity, tobacco smoking, and alcohol consumption) and identify correlationsbetween these and sociodemographic characteristics in western and central Nicaragua.Methods. This was a cross-sectional study of 1 355 participants from six communitiesin Nicaragua conducted in September 2007–July 2009. Demographic and NCD risk-relatedhealth behavior information was collected from each individual, and their body mass index(BMI), blood pressure, diabetes status, and renal function were assessed. Data were analyzedusing descriptive statistics, bivariate analyses, and (non-stratified and stratified) logisticregression models.Results. Of the 1 355 study participants, 22.0% were obese and 55.1% were overweight/obese. Female sex, higher income, and increasing age were significantly associated with obesity.Among men, lifelong urban living correlated with obesity (Odds Ratio [OR] = 4.39,1.18–16.31). Of the total participants, 31.3% reported ever smoking tobacco and 47.7%reported ever drinking alcohol. Both tobacco smoking and alcohol consumption were strikinglymore common among men (OR = 13.0, 8.8–19.3 and 15.6, 10.7–22.6, respectively) andlifelong urban residents (OR = 2.42, 1.31–4.47 and 4.10, 2.33–7.21, respectively).Conclusions. There was a high prevalence of obesity/overweight across all income levels.Women were much more likely to be obese, but men had higher rates of tobacco and alcoholuse. The rising prevalence of NCD risk factors among even the poorest subjects suggests thatan epidemiologic transition in underway in western and central Nicaragua whereby NCDprevalence is shifting to all segments of society. Raising awareness that health clinics can beused for chronic conditions needs to be priority.

Objetivo. Describir la prevalencia de los factores de riesgo (sobrepeso/obesidad,tabaquismo y consumo de alcohol) de las enfermedades no transmisibles (ENT), ydeterminar las correlaciones entre estos y las características sociodemográficas en laszonas occidental y central de Nicaragua.Métodos. De septiembre del 2007 a julio del 2009, se llevó a cabo este estudio transversalen 1 355 participantes de seis comunidades de Nicaragua. Para cada persona,se recopiló información demográfica y sobre la conducta en materia de salud relacionadacon el riesgo de ENT, y se evaluaron el índice de masa corporal (IMC), la presiónarterial, la presencia o no de diabetes y la función renal. Se analizaron los datosmediante estadísticas descriptivas, análisis de dos variables, y modelos de regresiónlogística (análisis no estratificado y estratificado).Resultados. De los 1 355 participantes en el estudio, 22,0% eran obesos y 55,1%presentaban sobrepeso u obesidad. El sexo femenino, los ingresos más altos y la edadmás avanzada se asociaron significativamente con la obesidad. En los varones, laresidencia de por vida en un entorno urbano se correlacionó con la obesidad (razónde posibilidades [OR] = 4,39, 1,18–16,31). Del total de participantes, 31,3% habíanfumado tabaco y 47,7% habían consumido alcohol alguna vez. Tanto el tabaquismocomo el consumo de alcohol fueron considerablemente más frecuentes en los varones(OR = 13,0, 8,8–19,3 y 15,6, 10,7–22,6, respectivamente) y en los que residían de porvida en un entorno urbano (OR = 2,42, 1,31–4,47 y 4,10, 2,33–7,21, respectivamente).Conclusiones. Se observó una alta prevalencia de obesidad/sobrepeso en todos losniveles de ingresos. Las mujeres tenían muchas más probabilidades de ser obesas,pero los varones mostraban mayores tasas de tabaquismo y consumo del alcohol.

Prevalence of hypertension and associated risk factors in six Nicaraguan communities.

OBJECTIVE: Describe the prevalence of hypertension. DESIGN: Population based cross-sectional survey. SETTING: Six Nicaraguan communities with varying economies. PARTICIPANTS: 1,355 adults aged 20-60 years who completed both self-reported and quantitative measures of health. MAIN OUTCOME MEASURES: Prevalence of hypertension (systolic > or = 140 mm Hg, diastolic > or = 90 mm Hg, or self-reported medical history with diagnosis by a health care professional), uncontrolled hypertension (systolic > or = 140 mm Hg or diastolic > or = 90 mm Hg), diabetes (urinary glucose excretion > or = 100 mg/ dL or self-reported medical history diagnosed by a health care professional), and uncontrolled diabetes (urinary glucose excretion > or =100 mg/dL only). RESULTS: The prevalence of hypertension was 22.0% (19.2% in men, 24.2% in women). Blood pressure was controlled in 31.0% of male hypertensives and 55.1% of female hypertensives (odds ratio [OR] 2.86; 95% confidence interval [Cl] 1.74-4.69). Older age and higher body mass index were strongly associated with hypertension. Women who completed primary school had a lower risk of hypertension (OR .40; 95% Cl .19-.85) compared to those with no formal education. A history of living in both urban and rural settings was associated with lower prevalence of hypertension (OR .52; 95% CI .34-.79). Diabetes mellitus was found in 1.2% of men and 4.3% of women. Male sex was independently associated with decreased risk of diabetes (OR .31; 95% Cl .11-.86). CONCLUSIONS: At least one cardiovascular risk factor was found in half of this Nicaraguan sample. Cardiovascular risk factors should be the target of educational efforts, screening, and treatment.

Decreased kidney function among agricultural workers in El Salvador.

BACKGROUND: An epidemic of chronic kidney disease of unknown cause has emerged along the Pacific coast of Central America, particularly in relatively young male sugarcane workers. In El Salvador, we examined residence and occupations at different altitudes as surrogate risk factors for heat stress. STUDY DESIGN: Cross-sectional population-based survey. SETTING & PARTICIPANTS: Populations aged 20-60 years of 5 communities in El Salvador, 256 men and 408 women (participation, 73%): 2 coastal communities with current sugarcane and past cotton production and 3 communities above 500 m with sugarcane, coffee, and service-oriented economies. PREDICTOR: Participant sex, age, residence, occupation, agricultural history by crop and altitude, and traditional risk factors for CKD. OUTCOMES: Serum creatinine (SCr) level greater than the normal laboratory range for sex, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and proteinuria categorized as low (protein excretion ≥ 30-< 300 mg/dL) and high grade (≥ 300 mg/dL). RESULTS: Of the men in the coastal communities, 30% had elevated SCr levels and 18% had eGFR < 60 mL/min/1.73 m2 compared with 4% and 1%, respectively, in the communities above 500 m. For agricultural workers, prevalences of elevated SCr levels and eGFR < 60 mL/min/1.73 m2 were highest for coastal sugarcane and cotton plantation workers, but were not increased in sugarcane workers at 500 m or subsistence farmers. Women followed a weaker but similar pattern. Proteinuria was infrequent, of low grade, and not different among communities, occupations, or sexes. The adjusted ORs of decreased kidney function for 10-year increments of coastal sugarcane or cotton plantation work were 3.1 (95% CI, 2.0-5.0) in men and 2.3 (95% CI, 1.4-3.7) in women. LIMITATIONS: The cross-sectional nature of the study limits etiologic interpretations. CONCLUSION: Agricultural work on lowland sugarcane and cotton plantations was associated with decreased kidney function in men and women, possibly related to strenuous work in hot environments with repeated volume depletion.

Nicaragua revisited: evidence of lower prevalence of chronic kidney disease in a high-altitude, coffee-growing village.

BACKGROUND: Chronic kidney disease (CKD) is found at epidemic levels in certain populations of the Pacific Coast in northwestern Nicaragua especially in younger men. There are knowledge gaps concerning CKD's prevalence in regions at higher altitudes. METHODS: A cross-sectional study of adults between the ages of 20 and 60 years in 1 coffee-growing village in Nicaragua located at 1,000 m above sea level (MASL) altitude was performed. Predictors included participant sex, age, occupation, conventional CKD risk factors and other factors associated with CKD suggested by previous surveys in Central America. Outcomes included serum creatinine (SCr) values >1.2 mg/dL for men and >0.9 mg/dL for women, estimated glomerular filtration rate (GFR) <60 ml/min per 1.73 m2, dipstick proteinuria stratified as microalbuminuria (30-300 mg/dL) and macroalbuminuria (>300 mg/dL), hypertension and body mass index. RESULTS: Of 324 eligible participants, 293 were interviewed (90.4%), and 267 of those received the physical exam (82.4% overall). Of the sample, 45% were men. Prevalence rate of estimated GFR <60 ml/min per 1.73 m2 was 0 for men (0%) and 2 for women (1.4%). The prevalence of at least microalbuminuria was significantly higher among men compared with women (27.5% vs. 21.4%, respectively; p=0.02). CONCLUSIONS: The CKD prevalence in this village is comparable to a previously studied Nicaraguan coffee-farming region and much lower than previously screened portions of northwestern Nicaragua. There is heterogeneity in CKD prevalence across Nicaragua. At this time, screenings should target individuals living in previously identified, higher risk regions. More work is needed to understand determinants of CKD in this resource-poor nation.