In El Salvador, chronic kidney disease had reached epidemic proportions towards the end of this century’s first decade. In 2011–2012, the Ministry of Health reported it was the leading cause of hospital deaths in men, the fifth in women, and the third overall in adult hospital fatalities. Farming was the most common occupation among men in dialysis (50.7%). By 2017, chronic kidney disease admissions had overwhelmed hospital capacity. In 2009, El Salvador’s Ministry of Health, Cuba’s Ministry of Public Health and PAHO launched a cooperative effort to comprehensively tackle the epidemic. The joint investigations revealed a total prevalence of chronic kidney disease in the adult population of farming communities higher than that reported internationally (18% vs.11%–14.8%), higher in men than in women (23.9% vs 13.9%) and higher in men who were farmers/farmworkers than in men who were not (31.3% vs. 14.8%). The disease was also detected in children. An association was found between chronic kidney disease and exposure to agrochemicals (OR 1.4–2.5). In 51.9% of all chronic kidney disease cases, traditional causes (diabetes, hypertension, glomerulopathies, obstructive nephropathies and cystic diseases) were ruled out and the existence of a particular form of chronic kidney disease of nontraditional etiology was confirmed (whose initial cases were reported as early as 2002). In the patients studied, functional alterations and histopathologic diagnosis confirmed a chronic tubulointerstitial nephritis; most presented with neurosensory hearing loss, altered tendon reflexes and tibial artery damage. The main results of this cooperation were the epidemiologic, physiopathologic, clinical and histopathologic characterization of chronic kidney disease of nontraditional etiology. This characterization facilitated case definition for the epidemic and led to the hypothesis of systemic toxicity from agrochemicals (e.g., paraquat, glyphosate), which particularly affect the kidneys and to which farmers/farmworkers (who may also become dehydrated in the fields) are most exposed. The research thus also laid the foundations for design of comprehensive intersectoral government actions to reduce cases and put an end to the epidemic. Chronic kidney disease; chronic renal failure; tubulointerstitial nephritis; epidemiology; histopathology; international cooperation; agrochemicals; environmental pollutants, noxae, and pesticides; occupational health; PAHO; El Salvador; Cuba

ABSTRACT INTRODUCTION Chronic kidney disease has reached epidemic levels in several Central American countries since the early years of this century. In El Salvador, it is the second cause of death in men, the fifth in persons over 18 years old and the third cause of hospital deaths in the adult population. Its features, especially those of a subtype unassociated with traditional risk factors such as diabetes and high blood pressure, are only partially understood. OBJECTIVE Estimate the magnitude of chronic kidney disease in the adult population of El Salvador, considering both prevalence of the disease in its diverse forms as well as presence of potential risk factors nationally and in major subpopulations. METHODS A descriptive, cross-sectional analysis was conducted on data obtained from the Survey of Chronic Non-communicable Diseases in Adults in El Salvador, completed in 2015. The original data (interviews and measurements) were collected between October 2014 and March 2015 from 4817 adults employing a two-stage probabilistic cluster sample, with stratification of primary sampling units. Our analysis, using 20 of the 118 primary variables included in the original survey, focused on point estimation of prevalence rates and means, related to both traditional biological risk factors and nontraditional ones, such as insufficient hydration, strenuous working conditions and exposure to toxic agents. A separate analysis was performed to estimate prevalence of chronic kidney disease from nontraditional causes. Corresponding confidence intervals were calculated with proper weighting. RESULTS The general prevalence of chronic kidney disease in El Salvador was 12.8% (men 18.0%; women 8.7%). Of the chronically ill kidney patients, 13.1% were between 20 and 40 years of age. Among biological risk factors, the most frequent was high blood pressure (37.0%). Among nontraditional risk factors, high levels of sugary drink consumption (81.0%), insufficient hydration (65.9%) and high levels of exposure to agrochemicals in the work environment (12.6%) were also observed. Prevalence of chronic kidney disease from nontraditional causes was 3.9% (men 6.1%; women 2.2%). CONCLUSIONS Chronic kidney disease has reached epidemic proportions in El Salvador. The data confirm a health tragedy that, although especially striking older men, also takes a severe toll on young men and women. The results confirm findings of previous research in several Salvadoran agricultural communities. The relatively high level of population exposure to agrochemicals is important and alarming, especially in rural areas, meriting health-impact studies that include and go beyond possible impact on chronic kidney disease.

ABSTRACT INTRODUCTION For two decades, various countries have experienced an epidemic of chronic kidney disease unexplainable by traditional causes. Typically a chronic tubulointerstitial nephritis, it predominantly affects young male agricultural workers and has been reported in several countries in Central America, as well as in Sri Lanka, India and Egypt. Recent studies in El Salvador have also reported the disease in male nonagricultural workers and in women, both those working in agriculture and not. Epidemiological information on whether this condition affects pediatric populations is virtually nonexistent. Globally, estimates of chronic kidney disease prevalence in pediatric populations range from 21 to 108 per million population. OBJECTIVE Determine the prevalence of urinary markers of renal damage and of chronic kidney disease in persons aged <18 years in rural Salvadoran communities. METHODS Pediatric NefroSalva was a descriptive epidemiologic study in three agricultural regions with known high prevalence of chronic kidney disease of uncertain etiology: Bajo Lempa, Guayapa Abajo and Las Brisas. Demographic and health data were collected and physical measurements were taken for 2115 persons aged <18 years, 1058 boys and 1057 girls. Urine samples were tested for markers of renal damage and blood samples analyzed to measure creatinine for estimating glomerular filtration rate (Schwartz formula). Median glomerular filtration rate was compared with reference values for age groups 2-12 and 13-17 years; mean glomerular filtration rate trends were assessed for age groups 2-5, 6-12 and 13-17 years. Positive test results were confirmed after three months. RESULTS Prevalence of urinary markers of renal damage was 4%, 4.3% in girls and 3.8% in boys. Microalbuminura (albumin:creatinine ratio 30-300 mg/g) was detected in both sexes and all age groups in all three regions, with prevalences of 2.6%-3.8% in boys and 3.3%-3.8% in girls. Macroalbuminuria (albumin:creatinine ratio >300 mg/g) was detected only in girls in Las Brisas, 2.3%. Glomerular hyperfiltration (compared to international norms) was found in all age-sex groups in all three regions. Prevalence of chronic kidney disease was 3.9%—4.1% in girls and 3.6% in boys. The prevalence of chronic renal failure was 0.1%. CONCLUSIONS High prevalence of chronic kidney disease in children and adolescents calls attention to the need for primary prevention from very early ages. This finding in children in areas where chronic kidney disease of uncertain etiology is common in adults is consistent with a contribution of environmental toxins to the epidemic observed in these areas.

INTRODUCTION: Chronic kidney disease is a serious health problem in El Salvador. Since the 1990s, there has been an increase in cases unassociated with traditional risk factors. It is the second leading cause of death in men aged >18 years. In 2009, it was the first cause of in-hospital death for men and the fifth for women. The disease has not been thoroughly studied. OBJECTIVE: Characterize clinical manifestations (including extrarenal) and pathophysiology of chronic kidney disease of nontraditional causes in Salvadoran farming communities. METHODS: A descriptive clinical study was carried out in 46 participants (36 men, 10 women), identified through chronic kidney disease population screening of 5018 persons. Inclusion criteria were age 18 - 59 years; chronic kidney disease at stages 2, 3a and 3b, or at 3a and 3b with diabetes or hypertension and without proteinuria; normal fundoscopic exam; no structural abnormalities on renal ultrasound; and HIV-negative. Examinations included social determinants; psychological assessment; clinical exam of organs and systems; hematological and biochemical parameters in blood and urine; urine sediment analysis; markers of renal damage; glomerular and tubular function; and liver, pancreas and lung functions. Renal, prostate and gynecological ultrasound; and Doppler echocardiography and peripheral vascular and renal Doppler ultrasound were performed. RESULTS: Patient distribution by chronic kidney disease stages: 2 (32.6%), 3a (23.9%), 3b (43.5%). Poverty was the leading social determinant observed. Risk factor prevalence: agrochemical exposure (95.7%), agricultural work (78.3%), male sex (78.3%), profuse sweating during work (76.3%), malaria (43.5%), NSAID use (41.3%), hypertension (36.9%), diabetes (4.3%). General symptoms: arthralgia (54.3%), asthenia (52.2%), cramps (45.7%), fainting (30.4). Renal symptoms: nycturia (65.2%), dysuria (39.1%), foamy urine (63%). Markers of renal damage: macroalbuminuria (80.4%), β2 microglobulin (78.2%), NGAL (26.1%). Renal function: hypermagnesuria (100%), hyperphosphaturia (50%), hypernatriuria (45.7%), hyperkaluria (23.9%), hypercalciuria (17.4%), electrolyte polyuria (43.5%), metabolic alkalosis (45.7%), hyponatremia (47.8%), hypocalcemia (39.1%), hypokalemia (30.4%), hypomagnesemia (19.6%). Imaging: Ultrasound showed fatty liver (93.5%) and vascular Doppler showed tibial artery damage (66.7%). Neurological symptoms: abnormal tendon reflexes (45.6%), Babinski sign and myoclonus (6.5%), sensorineural hearing loss (56.5%). CONCLUSIONS: This chronic kidney disease studied behaves clinically like chronic tubulointerstitial nephropathy, but with systemic manifestations not attributable to kidney disease. While male agricultural workers predominated, women and adolescents were also affected. Findings support a hypothesis of multifactorial etiology with a key role played by nephrotoxic environmental agents.

INTRODUCTION: Chronic kidney disease is a global pandemic, affecting the majority of countries in the world. Its prevalence is approximately 10% and it is associated mainly with diabetes and high blood pressure. In El Salvador, it is the leading cause of hospital deaths among men. OBJECTIVE: Determine prevalence of chronic kidney disease and its risk factors in two Salvadoran farming communities. METHODS: From March through September 2012, a descriptive cross-sectional study was conducted in two Salvadoran farming communities: Dimas Rodríguez (El Paisnal municipality) and El Jícaro (San Agustín municipality). The research involved both epidemiological and clinical methods. An active search for chronic kidney disease and its risk factors was carried out in the population aged >15 years. House-to-house visits were carried out to take family and individual health histories and gather data on social conditions and risk factors. A physical examination was performed, along with laboratory tests (urinalysis and blood chemistry) to measure renal function and detect markers for renal damage. RESULTS: A total of 223 persons of both sexes were studied. Overall prevalence of chronic kidney disease was 50.2%. Prevalence of chronic renal failure was 16.1%, with slight variations between the sexes. In El Jícaro, 77.3% of participants reported contact with agrochemicals and 76.6% were farmworkers; the respective figures for Dimas Rodríguez were 75.8% and 73.7%. The next most frequently reported risk factor was NSAID use, at 61.7% in El Jícaro and 77.9% in Dimas Rodríguez. CONCLUSIONS: CKD prevalence is alarming in these communities, among both young and old, men and women, independently of occupation. Health services must cope with the increased CKD burden observed, and are challenged to implement preventive strategies.

INTRODUCTION: For at least a decade, a chronic kidney disease unassociated with diabetes mellitus, hypertension or any of the more common traditional causes, has been reported in Salvadoran agricultural communities. OBJECTIVE: Characterize histopathology of chronic kidney disease of unknown etiology in patients from Salvadoran agricultural communities, describe renal damage associated with each disease stage, and assess associations between histopathological alterations and sociodemographic variables. METHODS: The study involved 46 patients of both sexes, aged ≥18 years. After clinical, laboratory and imaging examinations, kidney biopsies were performed and renal tissue assessed for interstitial fibrosis, tubular atrophy, interstitial inflammatory infiltration, sclerosis, increase in glomerular size and extraglomerular vascular lesions (according to the Banff 97 classification used for kidney transplant rejection). Special staining was done: Schiff periodic acid, Masson trichrome and methenamine silver. Immunofluorescence techniques were used to evaluate IgA, IgG, IgM, complement C1q and C3, fibrin, and kappa and lambda light chain deposits. RESULTS: The main findings were interstitial fibrosis and tubular atrophy with or without inflammatory monocyte infiltration. In addition, generalized sclerosis, increased glomerular size, collapse of some glomerular tufts, and lesions of extraglomerular blood vessels (such as intimal proliferation and thickening and vacuolization of the tunica media) were observed. Interstitial fibrosis and glomerulosclerosis were associated with male sex. Sugarcane workers showed more interstitial fibrosis and tubular atrophy and less glomerulomegaly than other occupational groups. CONCLUSION: The morphological pattern in all biopsies was one of chronic tubulointerstitial nephropathy with secondary glomerular and vascular damage, in different stages of evolution of chronic kidney disease, independent of age, sex or occupation.

In recent years, Central America, Egypt, India and Sri Lanka have reported a high prevalence of chronic kidney disease of unknown etiology in agricultural communities, predominantly among male farmworkers. This essay examines the disease's case definitions, epidemiology (disease burden, demographics, associated risk factors) and causal hypotheses, by reviewing published findings from El Salvador, Nicaragua, Costa Rica, Sri Lanka, Egypt and India. The range of confirmed chronic kidney disease prevalence was 17.9% - 21.1%. Prevalence of reduced glomerular filtration (<60 mL/min/1.73 m² body surface area) based on a single serum creatinine measurement was 0% - 67% men and 0% - 57% women. Prevalence was generally higher in male farmworkers aged 20 - 50 years, and varied by community economic activity and altitude. Cause was unknown in 57.4% - 66.7% of patients. The dominant histopathological diagnosis was chronic tubulointerstitial nephritis. Associations were reported with agricultural work, agrochemical exposure, dehydration, hypertension, homemade alcohol use and family history of chronic kidney disease. There is no strong evidence for a single cause, and multiple environmental, occupational and social factors are probably involved. Further etiological research is needed, plus interventions to reduce preventable risk factors.

INTRODUCTION: In El Salvador, chronic kidney disease is a serious and growing public health problem. Chronic renal failure was the first cause of hospital deaths in men and the fifth in women in 2011. OBJECTIVE: Determine prevalence of CKD, CKD risk factors (traditional and nontraditional) and renal damage markers in the adult population of specific rural areas in El Salvador; measure population distribution of renal function; and identify associated risk factors in CKD patients detected. METHODS: A cross-sectional analytical epidemiological study was conducted based on active screening for chronic kidney disease and risk factors in persons aged ≥18 years during 2009 - 2011. Epidemiological and clinical data were gathered through personal history, as well as urinalysis for renal and vascular damage markers, determinations of serum creatinine and glucose, and estimation of glomerular filtration rates. Chronic kidney disease cases were confirmed at three months. Multiple logistical regression was used for statistical analysis. RESULTS: Prevalence of chronic kidney disease was 18% (23.9% for men and 13.9% for women) in 2388 persons: 976 men and 1412 women from 1306 families studied. Chronic kidney disease with neither diabetes nor hypertension nor proteinuria ≥1 g/L (51.9%) predominated. Prevalence of chronic renal failure was 11% (17.1% in men and 6.8% in women). Prevalence of renal damage markers was 12.5% (higher in men): microalbuminuria, 6.9%; proteinuria (0.3 g/L), 1.7%; proteinuria (1g/L), 0.6%; proteinuria (2 g/L), 0.4 %; and hematuria, 1.5%. Prevalence of chronic kidney disease risk factors was: diabetes mellitus, 9%; hypertension, 20.9%; family history of chronic kidney disease, 16.5%; family history of diabetes mellitus, 18.5%; family history of hypertension, 30.6%; obesity, 21%; central obesity, 24.9%; NSAID use, 84.2%; smoking, 9.9%; alcohol use, 15%; agricultural occupation, 31.2%; and contact with agrochemicals, 46.7%. Chronic kidney disease was significantly associated with male sex, older age, hypertension, agricultural occupation, family history of chronic kidney disease and contact with the agrochemical methyl parathion. CONCLUSIONS: The results of this study support suggestions from other research that we are facing a new form of kidney disease that could be called agricultural nephropathy.

INTRODUCTION: Chronic kidney disease of unknown etiology is occurring in various geographic areas worldwide. Cases lack typical risk factors associated with chronic kidney disease, such as diabetes and hypertension. It is epidemic in El Salvador, Central America, where it is diagnosed with increasing frequency in young, otherwise-healthy male farmworkers. Suspected causes include agrochemical use (especially in sugarcane fi elds), physical heat stress, and heavy metal exposure. OBJECTIVE: To evaluate the geographic relationship between unspecifi ed chronic kidney disease (unCKD) and nondiabetic chronic renal failure (ndESRD) hospital admissions in El Salvador with the proximity to cultivated crops and ambient temperatures. METHODS: Data on unCKD and ndESRD were compared with environmental variables, crop area cultivated (indicator of agrochemical use) and high ambient temperatures. Using geographically weighted regression analysis, two model sets were created using reported municipal hospital admission rates per ten thousand population for unCKD 2006- 2010 and rates of ndESRD 2005-2010. These were assessed against local percent of land cultivated by crop (sugarcane, coffee, corn, cotton, sorghum, and beans) and mean maximum ambient temperature, with Moran’s indices determining data clustering. Two-dimensional geographic models illustrated parameter spatial distribution. RESULTS: Bivariate geographically weighted regressions showed statistically signifi cant correlations between percent area of sugarcane, corn, cotton, coffee, and bean cultivation, as well as mean maximum ambient temperature with both unCKD and ndESRD hospital admission rates. Percent area of sugarcane cultivation had greatest statistical weight (p < 0.001; Rp² = 0.77 for unCKD). The most statistically signifi cant multivariate geographically weighted regression model for unCKD included percent area of sugarcane, cotton and corn cultivation (p < 0.001; Rp² = 0.80), while, for ndESRD, it included the percent area of sugarcane, corn, cotton and coffee cultivation (Rp² = 0.52). Univariate unCKD and ndESRD Moran�fs I (0.20 and 0.33, respectively) indicated some degree of clustering. Ambient temperature did not improve multivariate geographically- weighted regression models for unCKD or ndESRD. Local bivariate Moran�fs indices with relatively high positive values and statistical signifi cance (0.3.1.0, p < 0.05) indicated positive clustering between unCKD hospital admission rates and percent area of sugarcane as well as cotton cultivation. The greatest positive response for clustering values did not consistently plot near the highest temperatures; there were some positive clusters in regions of lower temperatures. Clusters of ndESRD were also observed, some in areas of relatively low chronic kidney disease incidence in western El Salvador. CONCLUSIONS: High temperatures do not appear to strongly infl uence occurrence of unCKDu proxies. CKDu in El Salvador may arise from proximity to agriculture to which agrochemicals are applied, especially in sugarcane cultivation. The fi ndings of this preliminary ecological study suggest that more research is needed to assess and quantify presence of specifi c agrochemicals in high-CKDu areas.

This study aimed to identify the use of native tropical timber resources in the Emilio Rabasa community located in the Ocote Forest Biosphere Reserve, in Chiapas state, Mexico. 30 semi-structured surveys were conducted with ejidatarios "land-owners", and several specimens were collected for their identification. A total of 35 native timber species were determined, included in 31 genera and 24 families.The main multipurpose timber species mentioned were bojón (Cordia alliodora (R. & P.) Oken), palo amarillo (Terminalia obovata (R. & P.) Steud), mahogany (Swietenia macrophylla G. King), the jolocín (Heliocarpus donnell-smithii Rose), cedar (Cedrela odorata M. Roem. King) and copalchi (Croton guatemalensis Lotsy). Among the main uses that the community gives these timber species are 38% for extraction of firewood and fence posts, 17% for making tools and 16% for making furniture, construction and houses repair.

El presente estudio tuvo como finalidad conocer el aprovechamiento de los recursos maderables tropicales nativos por parte de la comunidad Emilio Rabasa, ubicada en la Reserva de la Biosfera Selva El Ocote, en el estado de Chiapas, México. Se realizaron encuestas semiestructuradas a 30 ejidatarios y se colectaron ejemplares para la identificación de las especies. Se determinó un total de 35 especies maderables nativas, incluidas en 31 géneros y 24 familias. Las principales especies maderables multipropósito mencionadas fueron el bojón (Corda alliodora (R. & P.) Oken), el palo amarillo (Terminalia obovata (R. & P.) Steud) la caoba (Swietenia macrophylla G. King), el jolocín (Heliocarpus donnell-smithii Rose), el cedro (Cedrela odorata M. Roem. King) y el copalchi (Croton guatemalensis Lotsy). Entre los principales usos que la comunidad le da a las especies maderables está, 38% la extracción de leña y postes para cercado, 17% para la elaboración de herramientas de trabajo y 16% para la elaboración de muebles, construcción y reparación de casas.

INTRODUCTION: In El Salvador, end-stage renal disease is the leading cause of hospital deaths in adults, the second cause of death in men and the fifth leading cause of death in adults of both sexes in the general population. OBJECTIVE: Identify risk factors for chronic kidney disease and urinary markers of renal and vascular damage, measure kidney function and characterize prevalence of chronic kidney disease in persons aged >18 years in the Bajo Lempa region of El Salvador. METHODS: A cross-sectional analytical epidemiological study was carried out using active screening for chronic kidney disease and associated risk factors in individuals aged >18 years in the Bajo Lempa Region, a rural, coastal area in El Salvador. Door-to-door visits and clinical examinations were conducted. Epidemiological and clinical data were collected including: family and personal clinical history of disease; biological, behavioral, social and environmental risk factors; physical measurements; urinalysis for markers of renal and vascular damage; and blood tests (serum creatinine, serum glucose, lipid profile). Glomerular filtration rate was calculated using the Modification of Diet in Renal Disease formula. Chronic kidney disease case confirmation was done three months later. Multiple logistic regression was used for data analysis. RESULTS: A total of 375 families and 775 individuals (343 men, 432 women) were studied-88.3% of the total resident population in the region. Elevated prevalence of risk factors was observed: diabetes mellitus, 10.3%; hypertension,16.9%; family history of chronic kidney disease, 21.6%; dyslipidemias, 63.1%; overweight, 34%; obesity, 22.4%; metabolic syndrome, 28.8%; use of non-steroidal anti-inflammatory drugs, 74.8%; infectious diseases, 86.9%; agricultural occupation, 40.6% (80.6% in men); and contact with agrochemicals, 50.3% (82.5% in men). Prevalence renal damage markers was 15.8% (greater in men): microalbuminuria 6.3%; proteinuria 5.7%; hematuria 3.5%; proteinuria-hematuria 0.3%. Proteinuria of <1 g/L predominated. Prevalence of chronic kidney disease was 17.9% (25.7% in men; 11.8% in women). Distribution by stages: stage 1, 4.6%; stage 2, 3.5%; stage 3, 6.2%; stage 4, 3.0%; stage 5, 0.6%. In patients with chronic kidney disease, most common was non-diabetic chronic kidney disease (86.3%), followed by chronic kidney disease associated with neither diabetes nor hypertension (54.7%). Prevalence of chronic renal failure was 9.8% (17% in men; 4.1% in women). Multiple logistic regression showed significant association with increasing age, male sex, hypertension and family history of chronic kidney disease. CONCLUSIONS: Elevated prevalence of chronic kidney disease, chronic renal failure and risk factors was found, compared to international reports. Most common was chronic kidney disease of unknown cause, associated with neither diabetes nor hypertension. Associations were found with age, male sex, hypertension and family history of chronic kidney disease, with decline in kidney function beginning at early ages. Male farmers have a dual burden of non traditional (occupational, toxic environmental) and traditional (vascular) risk factors that could act in synergy, contributing to kidney damage.