Mesoamerican Nephropathy Research Articles

Prevalence of patients receiving renal replacement therapy in El Salvador in 2014

El Salvador has the highest renal failure mortality rate in the Americas. Five healthcare providers offer renal replacement therapy (RRT) in the country. The national RRT prevalence has never been reported. AimsTo determine the RRT prevalence in El Salvador and some basic characteristics. MethodsThe association of nephrology coordinated a nationwide cross-sectional survey during the third quarter of 2014. 31 renal centres participated in the survey, covering 99.5% of patients. ResultsNational RRT prevalence: 595 per million population (pmp), N=3807, average age 50.4 years old, 67.5% male. By modality: peritoneal dialysis (PD) 289pmp, haemodialysis (HD) 233pmp, with functioning kidney transplantation 74pmp (living donor only). Social security covers 25% of the population but treats 49.7% of RRT patients. Generally, higher prevalence was observed in municipalities with renal centres or located on the coast or lowlands. Ninety-five per cent of HD patients receive fewer than 3 weekly sessions. Of PD patients, 59% do not belong to a continuous outpatient or automated programme, and 25% still use rigid catheter. Aetiology of chronic kidney disease: unavailable/undetermined 50%, hypertension 21.1%, diabetes 18.9%, glomerulonephritis 6.7%, obstructive causes 1.2%, tubulointerstitial 0.9%, polycystic 0.4% and other 0.7%. DiscussionDespite the increase in RRT services, the prevalence is lower than the Latin American average (660pmp). Three quarters of HD and PD patients are under-dialysed. Obsolete RRT techniques are still used. The presence of Mesoamerican nephropathy influences the demographic characteristics (many young patients, two-thirds male, high prevalence in lowlands and coastlands).

Incidence, mortality, and prevalence of end-stage chronic renal disease in the Bajo Lempa region of El Salvador: A ten-year community registry

The Bajo Lempa is an impoverished rural coastal region of El Salvador affected by the chronic kidney disease (CKD) epidemic known as Mesoamerican nephropathy. The local community organisation Fondo Social de Emergencia para la Salud (FSES) (Emergency social fund for health) is helping to fight the epidemic in 42 communities of the region (19,223 inhabitants; average age 26.7 years; 48.5% male; 40.2% <18 years). ObjectivesTo report annual rates of end-stage renal disease (ESRD) incidence and patient mortality in these communities during a 10-year period (2004–2013), and the prevalence of patients receiving renal replacement therapy (RRT) as of 31 December 2013. MethodsThe FSES recorded new ESRD cases, basic patient history, form of RRT if received and patient deaths. ResultsWe registered 271 new ESRD cases (annual average 27.1; 89% male; average age 55.6 years, four <18 years). Average annual ESRD incidence rate: 1409.8 per million population (pmp). Two-thirds did not report diabetes or hypertension. 94 patients (34.7%) received RRT: 58 in the Ministry of health, 26 in private services, 9 in social security and 1 in the military health system. 246 patients died (annual average 24.6 deaths; 89.4% male; average age 56.1 years; 92.3% at home). Average annual mortality rate: 128/100,000 population. Prevalence of patients receiving RRT in 2013: 1300.5pmp (N=25; 84% male; average age 51 years). ConclusionsThis region has a high incidence of ESRD. Few receive RRT. Patient mortality is high even with RRT. Most patients are male (9:1). Social determinants influence the high mortality.

Characterization of Mesoamerican Nephropathy in a Kidney Failure Hotspot in Nicaragua.

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. Cross-sectional family-based study. 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. CKD defined as serum creatinine level≥ 1.5mg/dL in men and≥1.4mg/dL in women. Clinical and biochemical parameters, including serum sodium, potassium, bicarbonate, calcium, magnesium, phosphorus, and uric acid. 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. 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. 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.

Prevalencia de pacientes con tratamiento sustitutivo renal en El Salvador en 2014

El Salvador has the highest renal failure mortality rate in the Americas. Five healthcare providers offer renal replacement therapy (RRT) in the country. The national RRT prevalence has never been reported. AimsTo determine the RRT prevalence in El Salvador and some basic characteristics. MethodsThe association of nephrology coordinated a nationwide cross-sectional survey during the third quarter of 2014. 31 renal centres participated in the survey, covering 99.5% of patients. ResultsNational RRT prevalence: 595 per million population (pmp), N=3807, average age 50.4 years, 67.5% male. By modality: peritoneal dialysis (PD) 289 pmp, haemodialysis (HD) 233 pmp, with functioning kidney transplantation 74 pmp (living donor only). Social security covers 25% of the population but treats 49.7% of RRT patients. Generally, higher prevalence was observed in municipalities with renal centres or located on the coast or lowlands. Ninety-five percent of HD patients receive fewer than 3 weekly sessions. Of PD patients, 59% do not belong to a continuous outpatient or automated programme, and 25% still use rigid catheter. Aetiology of chronic kidney disease: unavailable/undetermined 50%, hypertension 21.1%, diabetes 18.9%, glomerulonephritis 6.7%, obstructive causes 1.2%, tubulointerstitial 0.9%, polycystic 0.4% and other 0.7%. DiscussionDespite the increase in RRT services, the prevalence is lower than the Latin American average (660 pmp). Three quarters of HD and PD patients are under-dialysed. Obsolete RRT techniques are still used. The presence of Mesoamerican nephropathy influences the demographic characteristics (many young patients, two-thirds male, high prevalence in lowlands and coastlands).

Incidencia, mortalidad y prevalencia de enfermedad renal crónica terminal en la región del Bajo Lempa, El Salvador: 10 años de registro comunitario

The Bajo Lempa is an impoverished rural coastal region of El Salvador affected by the chronic kidney disease (CKD) epidemic known as Mesoamerican nephropathy. The local community organisation Fondo Social de Emergencia para la Salud (FSES) (Emergency social fund for health) is helping to fight the epidemic in 42 communities of the region (19,223 inhabitants; average age 26.7 years; 48.5% male; 40.2% <18 years). ObjectivesTo report annual rates of end-stage renal disease (ESRD) incidence and patient mortality in these communities during a 10-year period (2004-2013), and the prevalence of patients receiving renal replacement therapy (RRT) as of 31 December 2013. MethodsThe FSES recorded new ESRD cases, basic patient history, form of RRT if received and patient deaths. ResultsWe registered 271 new ESRD cases (annual average 27.1; 89% male; average age 55.6 years, four <18 years). Average annual ESRD incidence rate: 1409.8 per million population (pmp). Two-thirds did not report diabetes or hypertension. 94 patients (34.7%) received RRT: 58 in the Ministry of health, 26 in private services, 9 in social security and 1 in the military health system. 246 patients died (annual average 24.6 deaths; 89.4% male; average age 56.1 years; 92.3% at home). Average annual mortality rate: 128/100,000 population. Prevalence of patients receiving RRT in 2013: 1300.5 pmp (N=25; 84% male; average age 51 years). ConclusionsThis region has a high incidence of ESRD. Few receive RRT. Patient mortality is high even with RRT. Most patients are male (9:1). Social determinants influence the high mortality.

Mesoamerican Nephropathy in Nicaragua: Acute Interstitial Nephritis of Infectious Origin?

Mesoamerican Nephropathy in Nicaragua: Acute Interstitial Nephritis of Infectious Origin?

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

BackgroundChronic 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. ObjectivesThe aim of the study was to examine whether kidney function changes over a few months of work during the harvest period. MethodsA 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. ResultsThe 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. ConclusionsThere 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.

The Mesoamerican nephropathy: a regional epidemic of chronic kidney disease?

The Mesoamerican nephropathy: a regional epidemic of chronic kidney disease?

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.

Overlooked Risk for Chronic Kidney Disease after Leptospiral Infection: A Population-Based Survey and Epidemiological Cohort Evidence.

BackgroundLeptospirosis is the most widespread zoonosis. Chronic human infection and asymptomatic colonization have been reported. However, renal involvement in those with leptospira chronic exposure remains undetermined.Methods and FindingsIn 2007, a multistage sampling survey for chronic kidney disease (CKD) was conducted in a southern county of Taiwan, an area with a high prevalence of dialysis. Additionally, an independent cohort of 88 participants from a leptospira-endemic town was followed for two years after a flooding in 2009. Risks of CKD, stages of CKD, associated risk factors as well as kidney injury markers were compared among adults with anti-leptospira antibody as defined by titers of microscopic agglutination test (MAT). Of 3045 survey participants, the individuals with previous leptospira exposure disclosed a lower level of eGFR (98.3±0.4 vs 100.8±0.6 ml/min per 1.73 m2, P<0.001) and a higher percentage of CKD, particularly at stage 3a-5 (14.4% vs 8.5%), than those without leptospira exposure. Multivariable linear regression analyses indicated the association of leptospiral infection and lower eGFR (95% CI -4.15 to -1.93, P < 0.001). In a leptospiral endemic town, subjects with a MAT titer ≥400 showed a decreased eGFR and higher urinary kidney injury molecule–1 creatinine ratio (KIM1/Cr) level as compared with those having lower titers of MAT (P<0.05). Furthermore, two participants with persistently high MAT titers had positive urine leptospira DNA and deteriorating renal function.Conclusions and SignificanceOur data are the first to show that chronic human exposure of leptospirosis is associated significantly with prevalence and severity of CKD and may lead to deterioration of renal function. This study also shed light on the search of underlying factors in areas experiencing CKD of unknown aetiology (CKDu) such as Mesoamerican Nephropathy.

Heat stress and workload associated with sugarcane cutting - an excessively strenuous occupation!

Chronic kidney disease not associated with traditional risk factors (sometimes called Mesoamerican nephropathy) is prevalent in male agricultural labourers, particularly sugarcane cutters, in Central America and Mexico regions [1]. Strenuous work in a hot environment with dehydration is believed to be a key causal factor [1]. The aim of this study was to assess the level of heat stress and workload in sugarcane cutters.

Heat stress, dehydration, and kidney function in sugarcane cutters in El Salvador – A cross-shift study of workers at risk of Mesoamerican nephropathy

BackgroundAn epidemic of progressive kidney failure afflicts sugarcane workers in Central America. Repeated high-intensity work in hot environments is a possible cause. ObjectivesTo assess heat stress, dehydration, biomarkers of renal function and their possible associations. A secondary aim was to evaluate the prevalence of pre-shift renal damage and possible causal factors. MethodsSugarcane cutters (N=189, aged 18–49 years, 168 of them male) from three regions in El Salvador were examined before and after shift. Cross-shift changes in markers of dehydration and renal function were examined and associations with temperature, work time, region, and fluid intake were assessed. Pre-shift glomerular filtration rate was estimated (eGFR) from serum creatinine. ResultsThe mean work-time was 4 (1.4–11) hours. Mean workday temperature was 34–36°C before noon, and 39–42°C at noon. The mean liquid intake during work was 0.8L per hour. There were statistically significant changes across shift. The mean urine specific gravity, urine osmolality and creatinine increased, and urinary pH decreased. Serum creatinine, uric acid and urea nitrogen increased, while chloride and potassium decreased. Pre-shift serum uric acid levels were remarkably high and pre-shift eGFR was reduced (<60mL/min) in 23 male workers (14%). ConclusionsThe high prevalence of reduced eGFR, and the cross-shift changes are consistent with recurrent dehydration from strenuous work in a hot and humid environment as an important causal factor. The pathophysiology may include decreased renal blood flow, high demands on tubular reabsorption, and increased levels of uric acid.

Mesoamerican nephropathy: geographical distribution and time trends of chronic kidney disease mortality between 1970 and 2012 in Costa Rica

ObjectivesMesoamerican nephropathy is an epidemic of chronic kidney disease (CKD) unrelated to traditional causes, mostly observed in sugarcane workers. We analysed CKD mortality in Costa Rica to explore when and...

Mesoamerican Nephropathy (MeN): A ‘New’ Chronic Kidney Disease related to Occupational Heat Exposure with Repeated Deprivation of Salts and Water

1Professor, Division of Renal Medicine, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm and Department of Evidence based Medicine, Stockholm County Council, Sweden 2Associate Professor, Division of Renal Medicine, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden 3Division of Renal Medicine, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden Received date: 30 June 2015; Accepted date: 21 August 2015; Published date: 25 August 2015.

Mesoamerican Nephropathy: Resolving the Enigma?

Mesoamerican Nephropathy: Resolving the Enigma?

Cyclical dehydration-induced renal injury and Mesoamerican nephropathy: as sweet by any other name?

Severe cyclical dehydration induces chronic renal injury in rodents. This effect is attenuated by global fructokinase deficiency, suggesting possible roles for fructokinase and fructose metabolism in mediating or promoting dehydration-induced injury. Clinical and pathological similarities between this injury model and endemic Mesoamerican nephropathy (MeN) have fueled speculation that dehydration-induced injury and MeN may share common mechanistic underpinnings involving fructokinase that can be targeted to mitigate disease development, progression, and/or severity.

0204 Mesoamerican nephropathy in Costa Rica: Geographical distribution and time trends of chronic kidney disease mortality between 1970 and 2012

ObjectivesTo characterise geographical distribution and time trends of chronic kidney disease (CKD) mortality in the context of the epidemic of Mesoamerican nephropathy (MeN), likely related to occupational heat stress and...

0401 Repeated pre and post-shift urinalyses show kidney dysfunction among Costa Rican sugarcane cutters exposed to heat stress

ObjectivesSugarcane harvesters in Costa Rica are exposed to heat stress, a likely major risk factor in the Mesoamerican nephropathy epidemic. Routine urinalyses provide important information about kidney function, but have...

Update on endemic nephropathies

A large number of patients worldwide suffer from chronic kidney disease (CKD) of unknown cause. Endemic nephropathies possibly contribute to this. The purpose of this review is to give a brief review of endemic nephropathies and to summarize what is known about their cause. The cause of Balkan endemic nephropathy was eventually resolved, after 50 years of research. The cause was exposure to aristolochic acid from food. A new type of endemic nephropathy has recently been identified in Central America; Mesoamerican nephropathy. This kidney disease mainly affects agricultural workers in hot climates. Renal biopsy studies suggest that repeated dehydration and kidney ischemia is involved in the pathogenesis. Endemic nephropathies may comprise an important cause of CKD. Epidemiological studies are needed to describe the occurrence and distribution of the diseases. However, biopsy studies, in combination with careful clinical evaluation of the patients, are necessary to find out the cause of endemic nephropathies and thereby help in their prevention.

Wesseling et al. Respond

We appreciate Ventres' observations and share his goal to reduce CKD incidence occupational, environmental, and health-related reforms that make this work [agricultural labor] more humane. In our summary of the workshop on the Mesoamerican nephropathy (MeN) in San Jose, Costa Rica, November 2012, we also noted the need for a broad understanding of the epidemic and we call readers' attention to the full report(1) that details the comprehensive discussion of the epidemic including the issues raised by Ventres. In the workshop, we took account of the several points raised in his letter, but in our editorial we wished to call special attention to the growing evidence of heat stress and dehydration as an essential cofactor in a likely multifactorial disease etiology. (Am J Public Health. Published online ahead of print January 16, 2014: e1. doi:10.2105/AJPH.2013.301803). (Less)