Epidemic of Chronic Kidney Disease of Nontraditional Etiology in El Salvador: Integrated Health Sector Action and South–South Cooperation
October 2019, Vol 21, No 4

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

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Características clínicas de la enfermedad renal crónica de causas no tradicionales en las comunidades agrícolas salvadoreñas
Enfermedad renal crónica azota comunidades agrícolas

INTRODUCCIÓN La enfermedad renal crónica es un serio problema de salud en El Salvador. Desde la década de 1990, allí ha habido un incremento de casos no asociados con factores de riesgo tradicionales. Es la segunda causa de muerte en hombres en edad > 18 años. En el 2009, fue la primera causa de muerte hospitalaria para los hombres y la quinta para las mujeres. La enfermedad no ha sidocompletamente estudiada.

OBJETIVO Caracterizar las manifestaciones clínicas (incluidas las extrarrenales) y la fisiopatología de la enfermedad renal crónica de causas no tradicionales en las comunidades agrícolas salvadoreñas.

MÉTODOS Se desarrolló un estudio clínico descriptivo en 46 participantes (36 hombres, 16 mujeres), identificados a través de un pesquisaje poblacional de enfermedad renal crónica en 5 018 personas. Los criterios de inclusión fueron: edad 18–59 años, enfermedad renal crónica en estadios 2, 3a y 3b, o en estadios 3a y 3b con diabetes o hipertensión y sin proteinuria; examen de fondo de ojo normal; ausencia de anormalidades estructurales en el ultrasonido y VIH-negativo. Los exámenes incluyeron determinantes sociales, evaluación psicológica, examen clínico por aparatos y sistemas, parámetros hematológicos y bioquímicos en sangre y orina, análisis del sedimento urinario, marcadores de daño renal, función glomerular y tubular, y las funciones de hígado, páncreas y pulmones. Se realizaron ultrasonido renal, prostático y ginecológico, Doppler ecocardiográfico y vascular periférico, y ultrasonido Doppler renal.

RESULTADOS La distribución de pacientes por estadios de enfermedad renal crónica: 2 (32.6%), 3a (23.9%), 3b (43.5%). La pobreza fue el principal determinante social observado. Prevalencia de factores de riesgo: exposición a agroquímicos (95.7%), trabajo agrícola (78.3%), sexo masculino (78.3%), sudoración profusa durante el trabajo (78.3%), malaria (43.5%), uso de AINES (41.3%), hipertensión (36.9%), diabetes (4.3%). Síntomas generales: artralgia (54.3%), astenia (52.2%), calambres (45.7%), desmayo (30.4%). Síntomas renales: nicturia (65.2%), disuria (39.1%), orina espumosa (63%). Marcadores de daño renal: macroalbuminuria (80.4%), β2 microglobulina (78.2%), NGAL (26.1%). Función renal: hipermagnesuria (100%), hiperfosfaturia (50%), hipernatriuria (45.7%), hiperpotasuria (23.9%), hipercalciuria (17.4%), poliuria electrolítica (43.5%), alcalosis metabólica (45.7%), hiponatremia (47.8%), hipocalcemia (39.1%), hipopotasemia (30.4%), hipomagnesemia (19.6%). Imágenes: el ultrasonido mostró hígado graso (93.5%) y el Doppler vascular mostró daño de las arterias tibiales (66.7%). Síntomas neurológicos: reflejos osteotendinosos anormales (45.6%), signo de Babinski y mioclonus (6.5%), hipoacusia neurosensorial (56.5%).

CONCLUSIONES Esta enfermedad renal crónica se comporta clínicamente como una nefropatía tubulointersticial crónica, pero con manifestaciones sistémicas no atribuibles a la enfermedad renal. Aunque los hombres agricultores predominaron, las mujeres y los adolescentes también estuvieron afectados. Los hallazgos apoyan una hipótesis de etiología multifactorial en la que juega un papel esencial la nefrotoxicidad por agentes del medioambiente.

PALABRAS CLAVE Enfermedad renal crónica, enfermedad ocupacional, nefropatía túbulointersticial, nefrotoxicidad, isquemia renal, determinantes sociales, El Salvador

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Epidemiología de la enfermedad renal crónica en los adultos de las comunidades agrícolas salvadoreñas
Enfermedad renal crónica azota comunidades agrícolas

INTRODUCCIÓN En El Salvador, la enfermedad renal crónica es un serio y creciente problema de salud pública. La insuficiencia renal crónica fue la primera causa de muerte hospitalaria en los hombres y la quinta en las mujeres en 2011.

OBJETIVO Determinar la prevalencia de los factores de riesgo de la ERC (tradicionales y no tradicionales) y los marcadores de daño renal en la población adulta de áreas rurales específicas en El Salvador; medir la función renal y su distribución en la población e identificar los factores de riesgo asociados en los pacientes detectados con ERC.

MÉTODOS Se realizó un estudio epidemiológico transversal y analítico basado en la pesquisa activa de enfermedad renal crónica y factores de riesgo en personas de edades >18 años durante 2009- 2011. Se recogieron los datos epidemiológicos y clínicos a través de la historia clínica personal, así como los análisis de orina para los marcadores de daño renal y vascular, las determinaciones de creatinina sérica y glucosa, y la estimación de la tasa de filtración glomerular. Se confirmaron los casos de enfermedad renal crónica a los tres meses. Se utilizó la regresión logística múltiple para el análisis estadístico.

RESULTADOS La prevalencia de enfermedad renal crónica fue 18% (23.9% para los hombres y 13.9% para las mujeres) en 2 388 personas: 976 hombres y 1 412 mujeres de 1 306 familias estudiadas. Predominó la enfermedad renal crónica sin diabetes, ni hipertensión arterial, ni proteinuria >1 g/L (51.9%). La prevalencia de insuficiencia renal crónica fue 11% (17.1% en los hombres y 6.8% en las mujeres). La prevalencia de marcadores de daño renal fue 12.5% (mayor en los hombres): microalbuminuria, 6.9%; proteinuria (0.3 g/L), 1.7%; proteinuria (1g/L), 0.6%; proteinuria (2 g/L), 0.4%; y hematuria, 1.5%. La prevalencia de factores de riesgo de la enfermedad renal crónica fue: diabetes mellitus 9%; hipertensión, 20.9%; la historia familiar de enfermedad renal crónica, 16.5%; la historia familiar de diabetes mellitus, 18.5%; la historia familiar de hipertensión, 30.6%; la obesidad, 21%; la obesidad central, 24.9%; el consumo de AINEs, 84.2%; la proporción de fumadores, 9.9%; el consumo de alcohol, 15%; la ocupación en la agricultura, 31.2%; y el contacto con agroquímicos, 46.7%. La enfermedad renal crónica se asoció significativamente con el sexo masculino, las edades más avanzadas, la hipertensión, la ocupación en la agricultura, la historia familiar de enfermedad renal crónica y el contacto con el agroquímico metil paratión.

CONCLUSIONES Los resultados de este estudio apoyan las sugerencias propuestas por otras investigaciones con respecto a que enfrentamos una nueva forma de enfermedad renal que podría denominarse nefropatía agrícola.

PALABRAS CLAVE Insuficiencia renal crónica, enfermedad renal crónica no diabética, nefrotoxicidad, nefropatía tubulointersticial crónica, El Salvador.

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Clinical Characteristics of Chronic Kidney Disease of Nontraditional Causes in Salvadoran Farming Communities
April 2014, Vol 16, No 2

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%), ß2 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.

KEYWORDS Chronic kidney disease, occupational disease, chronic tubulointerstitial nephropathy, nephrotoxicity, renal ischemia, social determinants, El Salvador

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Epidemiology of Chronic Kidney Disease in Adults of Salvadoran Agricultural Communities
April 2014, Vol 16, No 2

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.

KEYWORDS Chronic renal failure, nondiabetic chronic kidney disease, nephrotoxicity, chronic tubulointerstitial nephropathy, El Salvador


Errata:

The following errata have been corrected in all online versions of this article.

Page 25, Table 1, units of measurement for albuminuria are mg albumin per g creatinine.

Page 26, fi rst complete paragraph, the last line should read, “Most CKD patients (51.9%) had no DM, HT or proteinuria.”

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Chronic Kidney Disease and Associated Risk Factors in the Bajo Lempa Region of El Salvador: Nefrolempa Study, 2009
October 2011, Vol 13, No 4
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.
KEYWORDS Chronic kidney disease/epidemiology, risk factors, prevalence, occupational health, environmental health, pesticides, agrochemicals, El Salvador
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