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. KEYWORDS Chronic kidney disease, chronic renal failure, tubulointerstitial nephritis, epidemiology, histopathology, international cooperation, agrochemicals, environmental pollutants, noxae, and pesticides, occupational health, PAHO; El Salvador, Cuba

INTRODUCCIÓN Hace más de una década se ha reportado una enfermedad renal crónica de causa desconocida en las comunidades agrícolas salvadoreñas la cual no está asociada a diabetes mellitus, hipertensión arterial ni a ninguna de las enfermedades tradicionales que con más frecuencia la causan.

OBJETIVO Caracterizar histopatológicamente la enfermedad renal crónica de causa desconocida en pacientes de comunidades agrícolas salvadoreñas, describir la asociación del daño renal con cada estadio de la enfermedad y evaluar la asociación entre las alteraciones histopatológicas y las variables sociodemográficas.

MÈTODOS Se estudiaron 46 pacientes de ambos sexos con una edad >18 años. Después de haber sido evaluados desde el punto de vista clínico, analítico e imagenológico, se les realizó biopsia renal, las que se clasificaron teniendo en cuenta la fibrosis intersticial, la atrofia tubular, el infiltrado inflamatorio intersticial, la esclerosis, el aumento de tamaño glomerular, y las lesiones vasculares extraglomerulares, según la clasificación de Banff 97, que se emplea para el rechazo del injerto renal. Para ello se realizaron las coloraciones especiales: ácido peryódico de Schiff, tricrómica de Masson, plata metenamina y se hicieron técnicas de inmunofluorescencia para evaluar el depósito de IgA, IgG, IgM, C3, C1q, fibrina, cadenas ligeras kappa y lambda

RESULTADOS El hallazgo fundamental fue la fibrosis intersticial y la atrofia tubular con o sin infiltrado inflamatorio de células mononucleares. Se observó además esclerosis global, aumento de tamaño glomerular, colapso del ovillo en algunos glomérulos, lesiones de los vasos sanguíneos extraglomerulares como la proliferación de la capa íntima y el engrosamiento y la vacuolización de la capa media. La fibrosis intersticial y la glomeruloesclerosis se asociaron con el sexo masculino. Los trabajadores de la caña de azúcar mostraron más fibrosis intersticial y atrofia tubular y menos glomerulomegalia que el resto de los grupos.

CONCLUSIÓN El patrón morfológico evidente encontrado en todas las biopsias fue el de una nefropatía tubulointersticial crónica con daño glomerular y vascular secundario, en diferentes estadios de evolución de la enfermedad renal crónica, independientemente de la edad, el sexo, el lugar de residencia y la ocupación.

PALABRAS CLAVE Enfermedad renal crónica, nefropatía tubulointersticial crónica, nefritis tubulointersticial, glomeruloesclerosis, histopatología, El Salvador

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.

KEYWORDS Chronic kidney disease, chronic tubulointerstitial nephropathy, tubulointerstitial nephritis, glomerulosclerosis, histopathology, El Salvador