ABSTRACT Introduction: An epidemic of chronic kidney disease (CKD) of devastating consequences has been taking place in El Salvador over the last few decades. In a significant portion of affected subjects, no other common cause of chronic kidney disease is present, such as diabetes and hypertension. This illness is usually called Chronic Kidney Disease from Non-Traditional Causes (CKDnT). Previous studies have shown a high prevalence of exposure to agrochemicals in affected populations, particularly in rural areas. In addition to sustained exposure to agrochemicals, the other leading hypothesis to explain this epidemic is prolonged exposure to high temperatures and dehydration in a context of exhausting agricultural work. Objectives: To assess the possible causal effect of exposure to agrochemicals in the emergence of the CKD epidemic in the adult population of El Salvador. Methods: We conducted a case-control analysis based on the 2015 survey of Chronic Diseases in Adults in El Salvador, a national probabilistic sample that covered 4,817 adults ≥20 years old. Those suffering from CKD were considered cases; the rest were managed as controls. Self-reported agrochemical exposures, other risk factors and health conditions were recorded. For binary exposures, the odds ratio (OR) of CKD and CKDnT was estimated. For variables measuring length of exposure, the average values for cases and for controls were compared. In all cases, the corresponding 95% confidence intervals were calculated. Multivariate logistic regression was used to examine the association between exposure to agrochemicals and CKD while controlling for potential confounding variables. Results: Regardless of how past exposure to agrochemicals was characterized (e.g., contact with paraquat or aerial fumigation) the OR of both CKD and CKDnT was always greater than 1.0 (range, 1.36 to 3.75). Similarly, the average number of years of exposure was consistently higher for cases than for controls for all continuous variables examined (greater than 2 years in most cases). Conclusions: The results of this study are consistent with previous epidemiologic and toxicological evidence and support the hypothesis that exposure to agrochemicals may be causally implicated in the ongoing CKD epidemics in El Salvador.

RESUMEN Introducción: Durante las últimas décadas, una epidemia de enfermedad renal crónica (ERC) de consecuencias devastadoras ha tenido lugar en El Salvador. Una parte importante de los sujetos afectados, no padece de una causa frecuente para padecer enfermedad renal crónica, tal como como diabetes e hipertensión. En tal caso, suele distinguirse la dolencia mediante el nombre de Enfermedad Renal Crónica de Causas no Tradicionales (ERCnT). Estudios previos muestran una alta prevalencia de exposición a agroquímicos en las poblaciones afectadas, particularmente en las zonas rurales. Además de la exposición sostenida a agroquímicos, la otra hipótesis principal para explicar esta epidemia es la exposición prolongada a altas temperaturas y deshidratación, en un contexto de trabajo agrícola agotador. Objetivos: Evaluar el posible efecto causal de la exposición a agroquímicos en la irrupción de la epidemia de ERC en la población adulta de El Salvador. Métodos: Se realizó un estudio de casos y controles, a partir de la Encuesta de Enfermedades Crónicas no Transmisibles en Adultos en El Salvador, basada en una muestra probabilística nacional que abarcó 4,817 adultos de 20 o más años de edad, concluida en 2015. Fueron considerados “casos” todos aquellos que padecían ERC; el resto dos restantes participantes se manejaron como controles. Se registraron las exposiciones a agroquímicos, así como a otros factores de riesgo y condiciones de salud según testimonio de los participantes. Para las exposiciones binarias, se estimó la razón de odds (OR) con respecto a padecer ERC y ERCnT. Para las variables que medían la duración de la exposición, se compararon los valores medios para casos y controles. En todos los casos, se calcularon los respectivos intervalos de confianza al 95%. Se utilizó la regresión logística multivariada para examinar la asociación entre la exposición a agroquímicos y la ERC, controlando las posibles variables confusoras. Resultados: Independientemente de cómo fuera caracterizada la exposición pasada a agroquímicos (por ejemplo, contacto con paraquat o fumigación aérea), el OR de ERC y ERCnT siempre fue mayor que 1.0 (rango, 1.36 a 3.75). Del mismo modo, la media de años de exposición fue consistentemente más alta para los casos que para los controles, para todas las variables continuas examinadas (más de 2 años en la mayoría de los casos). Conclusiones: Los resultados de este estudio son consistentes con la evidencia epidemiológica y toxicológica previa y respaldan la hipótesis de que la exposición a agroquímicos puede estar causalmente implicada en la epidemia de ERC que se registra en El Salvador.

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.