Aurora Aragón

Decreased Kidney Function of Unknown Cause in Nicaragua: A Community-Based Survey

BACKGROUNDnEnd-stage kidney disease overwhelms health services in Central America. We determined prevalences of decreased kidney function in distinct populations in the most affected region of Nicaragua.nnnSTUDY DESIGNnCross-sectional survey.nnnSETTING & PARTICIPANTSnTotal populations aged 20-60 years of 5 villages in Northwest Nicaragua: mining/subsistence farming (elevation, 100-300 m above sea level), banana/sugarcane (100-300 m), fishing (0-100 m), services (0-100 m), and coffee (200-675 m); 479 men and 617 women (83% response).nnnPREDICTOR OR FACTORnVillage; participant sex, age, and occupation; conventional chronic kidney disease risk factors.nnnOUTCOMESnSerum creatinine (SCr) values greater than laboratory reference range for sex, estimated glomerular filtration rate <60 mL/min/1.73 m(2), proteinuria stratified in the low (dipstick protein excretion, 30-300 mg/dL) and high (>300 mg/dL) range.nnnRESULTSnPrevalences of abnormal SCr levels: 18% (of all men) and 5% (of all women); in the mining/subsistence farming village, 26% and 7%; banana/sugarcane, 22% and 6%; fishing, 13% and 4%; services, 0% and 1%; and coffee, 7% and 0%. Prevalences of estimated glomerular filtration rate <60 mL/min/1.73 m(2): 14% (of all men) and 3% (of all women); in the listed villages, 19% and 5%, 17% and 4%, 10% and 2%, 0% and 0%, and 7% and 0%, respectively. Proteinuria, predominantly in the low range, affected 14% and 11% of all men and women without marked differences between villages. By occupation, abnormal SCr levels occurred in 31% and 24% of male and female agricultural workers at 100-300 m above sea level, but not at higher altitudes, and also was high in male artisans (43%), construction workers (15%), and miners (14%). In logistic regression models, for the banana/sugarcane and mining/subsistence farming villages, high blood pressure and age were significant predictors of abnormal SCr levels in men, and for mining/subsistence farming, age in women.nnnLIMITATIONSnCausality is not addressed.nnnCONCLUSIONSnIn some Nicaraguan villages and population segments, men in particular show a high prevalence of decreased kidney function of unknown origin, possibly environmental or occupational.

Decreased Kidney Function Among Agricultural Workers in El Salvador

BACKGROUNDnAn 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.nnnSTUDY DESIGNnCross-sectional population-based survey.nnnSETTING & PARTICIPANTSnPopulations 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.nnnPREDICTORnParticipant sex, age, residence, occupation, agricultural history by crop and altitude, and traditional risk factors for CKD.nnnOUTCOMESnSerum 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).nnnRESULTSnOf 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.nnnLIMITATIONSnThe cross-sectional nature of the study limits etiologic interpretations.nnnCONCLUSIONnAgricultural 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.

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 24u2009h. 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.

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.

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

BACKGROUNDnChronic 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 CKDs prevalence in regions at higher altitudes.nnnMETHODSnA 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.nnnRESULTSnOf 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).nnnCONCLUSIONSnThe 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.

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 17–39u2005years: 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 <80u2005mL/min/1.73u2005m2) and workers with normal kidney function (eGFRCKD-EPI ≥80u2005mL/min/1.73u2005m2). 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) >20u2005mg/dL), high serum creatinine (SCr >1.2u2005mg/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 <80u2005mL/min/1.73u2005m2 reported a higher intake of water and lower intake of sugary beverages. Serum uric acid levels related strongly and inversely to eGFR levels (adj β −10.4u2005mL/min/1.73u2005m2, 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 β 8.1u2005mL/min/1.73u2005m2, 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.

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

BACKGROUNDnMesoamerican 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.nnnSTUDY DESIGNnCase series.nnnSETTINGS & PARTICIPANTSnIn 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 >xa03g/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.nnnOUTCOMESnRenal morphology, clinical, and biochemical characteristics, change in eGFR per year.nnnMEASUREMENTSneGFR was calculated using the CKD-EPI creatinine (eGFRcr), cystatin C (eGFRcys), and creatinine-cystatin C (eGFRcr-cys) equations.nnnRESULTSnIn 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 wasxa0-4.4±8.4 (range,xa0-27.7 to 10.2) mL/min/1.73m2 per year. Most patients had stopped working with sugarcane cultivation.nnnLIMITATIONSn3 biopsy specimens had 4 or fewer glomeruli.nnnCONCLUSIONSnThis 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.

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

OBJECTIVEnTo 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.nnnMETHODSnThis 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.nnnRESULTSnOf 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).nnnCONCLUSIONSnThere 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.

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

BackgroundAn 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.MethodsThe 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.ResultsWe 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 <90xa0mL/min/1.73xa0m2.ConclusionConducting 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 <90xa0mL/min/1.73xa0m2 at baseline.

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.