At first, COVID-19 was thought to be primarily a respiratory disease, progressing in some patients to serious respiratory symptoms, pneumonia, severe respiratory distress syndrome and even death. Later analysis revealed entire systems were compromised, affecting other vital organs, including the kidneys, and a correlation was observed between chronic kidney disease (CKD) and COVID-19 severity.[1,2] This […]

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

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.

KEYWORDS Kidney, renal insufficiency, chronic, risk factors, epidemics, El Salvador

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.

KEYWORDS Chronic kidney disease, chronic renal failure, chronic tubulointerstitial nephropathy, interstitial nephritis, glomerular hyperfiltration, child health, adolescent health, environmental health, El Salvador

The following error has been corrected in all online versions of this article.
Page 19, Table 4. The first two rows of data were misaligned by column. The corrected table is:

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

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

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.

En los últimos años, América Central, Egipto, India y Sri Lanka han reportado una alta prevalencia de enfermedad renal crónica de causa desconocida en comunidades agrícolas, predominantemente entre hombres agricultores. Este artículo examina las definiciones de caso de la enfermedad, la epidemiología (carga de enfermedad, características demográficas, factores de riesgo asociados) y las hipótesis causales, a través de la revisión de hallazgos publicados en El Salvador, Nicaragua, Costa Rica, Sri Lanka, Egipto e India. El rango de la prevalencia de enfermedad renal crónica confirmada fue del 17.9%–21.1%. La prevalencia de la filtración glomerular disminuida (<60 mL/min/1.73 m2 de superficie corporal) basada en la medición de una muestra única de creatinina sérica fue en los hombres de 0%–67% y en las mujeres de 0%–57%. La prevalencia fue generalmente mayor en hombres agricultores en las edades entre 20 y 50 años y varió por la actividad económica de la comunidad y la altitud. La causa fue desconocida en 57.4%–66.7% de los pacientes. El diagnóstico histopatológico dominante fue la nefritis tubulointersticial crónica. Se reportaron asociaciones con trabajo agrícola, exposición a agroquímicos, deshidratación, hipertensión, consumo de alcohol de producción doméstica e historia familiar de enfermedad renal crónica. No hay una evidencia fuerte para una causa única, y probablemente están involucrados múltiples factores ambientales, ocupacionales y sociales. Se requiere desarrollar nuevas investigaciones etiológicas, y más intervenciones para reducir los factores de riesgo prevenibles.

PALABRAS CLAVE Enfermedad renal crónica, prevalencia, factores de riesgo

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

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

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.”

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.

KEYWORDS: Chronic kidney disease, prevalence, risk factors

INTRODUCTION The disease complex comprised of atherosclerosis, chronic kidney disease (CKD) and other associated chronic vascular diseases is the leading cause of mortality worldwide. Microalbuminuria is a marker for vascular damage in the heart, kidney and brain. This paper presents selected findings of the clinical-epidemiological Isle of Youth Study (ISYS) of markers for kidney and vascular damage from chronic vascular diseases and their common risk factors in total population, focusing on Phase 2 reassessment (in 2010) of Phase 1 (2004 to 2006) results.

OBJECTIVES (1) Update the prevalence of risk factors in the study population aged ≥20 years (adult population). (2) Confirm presence of microalbuminuria in at-risk adults diagnosed as presumptive positives in Phase I. (3) Evaluate association between microalbuminuria and selected risk factors.

METHODS Of 3779 adults positive for microalbuminuria in ISYS Phase 1, 73.1% were reevaluated. The risk-factor questionnaire was re-administered and blood pressure, weight and height were measured. Blood was tested for creatinine, glycemia, cholesterol and triglycerides. Glomerular filtration rate was calculated using the Modification of Diet in Renal Disease (MDRD) formula. Albuminuria was measured in urine using Micral-Test (Germany) and albumin/creatinine ratio (ACR) by nephelometry. This paper uses ACR as the reference for analyzing risk factor associations. Double-entry tables were developed to analyze association among microalbuminuria, risk factors and co-morbidities.

RESULTS Most prevalent risks were hypertension, consumption of nonsteroidal anti-inflammatory drugs (NSAIDs), excess weight and hypertriglyceridemia. Microalbuminuria was confirmed in 18% of cases, using the same test. Elevated prevalence of microalbuminuria was positively associated with advancing age, male sex, underweight, smoking, NSAID use, dyslipidemia, hypertension, diabetes, heart disease and stroke.

CONCLUSIONS The at-risk cohort studied presented low levels of confirmation for positive microalbuminuria. Positive microalbuminuria stratified individuals at greatest risk, except for obesity.

KEYWORDS Chronic kidney disease, cardiovascular disease, risk factors, damage markers, albuminuria, microalbuminuria, Cuba

Introduction Obesity is a social disease constituting a global pandemic. It is present in 90% of diabetic and 65% of hypertensive patients. It is associated with cardiometabolic syndrome and with damaging physiopathological mechanisms, particularly for the vascular system and the kidneys. On Cuba’s Isle of Youth, a community-based epidemiological study of chronic kidney disease (CKD), hypertension (HTN), diabetes mellitus (DM) and cardio-cerebral vascular disease was carried out in total population, including an examination of common risk factors.

Objective Based on the Isle of Youth Study (ISYS) data, determine prevalence of obesity and overweight, and their association with CKD, HTN, DM, and shared risk factors for all these conditions in total population of the Isle of Youth, Cuba.

Methods Phase 1: Population diagnosis (November 2004-April 2006): 96.6% of the Isle of Youth’s total population (80,117) was studied, including all ages and both sexes. Information was offered to the public, and written informed consent obtained. Screening was conducted by participant questionnaire including risk factors, physical measurements (weight, height, blood pressure and body mass index), and a single first-morning urine sample to determine the presence of vascular-renal damage markers – proteinuria and hematuria (Combur 10 Test, Roche), and microalbuminuria (Micral Test, Roche). When results were positive, serum creatinine was determined and glomerular filtration rate (GFR) estimated with Modification of Diet in Renal Disease (MDRD) formula for adults and Schwartz formula for children <15 years. Data obtained were analyzed to determine association of participants’ nutritional status with prevalence of chronic kidney disease, hypertension and diabetes mellitus, as well as a set of common risk factors.

Results Population <20 years: Obesity prevalence 3.2%; positive urine markers in 56.9% of obese and 8.9% of non-obese participants; positive albuminuria in 38% of obese and 3% of non-obese. Obese participants were found to be hyperfiltrating. DM prevalence was 9.5% in obese and 1.1% in non-obese participants. Population ≥20 years: Overweight, 31.3%; obese, 13.4%. Positive markers in normal-weight, overweight and obese individuals were 18.3%, 21.2% and 32.7%, respectively; microalbuminuria values increased with weight. Obese individuals were found to be hyperfiltrating. HTN prevalence in normal-weight, overweight and obese individuals was 18.3%, 31.5%, and 51.0% respectively; DM rates were 2.8%, 5.2% y 11.3%, respectively.

Conclusion In Cuba, obesity poses significant risk for vascular and renal damage and should be the focus of increased prevention efforts.

Keywords Vascular diseases, chronic kidney disease, CKD, chronic kidney insufficiency, hypertension, diabetes mellitus, risk factors, obesity, overweight, body mass index, glomerular filtration rate

The methodology is described in detail for the population-based Isle of Youth Study (ISYS) for epidemiological evaluation of CKD associated with cardio-cerebral vascular disease, arterial hypertension, diabetes mellitus, and other risk factors.

Background: Chronic kidney disease emerges as an important and growing global health problem associated with an increase in the incidence and prevalence of the above mentioned diseases.

ISYS Objectives: Ascertain CKD morbidity and its relation to chronic vascular diseases and other risk factors in whole population of Cuba’s Isle of Youth special municipality.

Method: 96.6% of the Isle of Youth’s total population (80,117 inhabitants) was studied, all ages and both sexes, November 15, 2004-April 30, 2006. The public was offered general information on the objectives and benefits of the study, and participants provided informed consent. Active screening was performed via personal interview questionnaire and urine sample to determine markers of kidney damage: proteinuria and hematuria (Combur-10-Test) and microalbuminuria (Micral-Test), according to a diagnostic algorithm. For those testing positive for any marker, serum creatinine was studied and glomerular filtration rate (GFR) calculated – in adults by Cockcroft-Gault and Modification of Diet in Renal Disease (MDRD) formulas and in children aged <15 years, by Schwartz – to stratify CKD by stages. Blood pressure, height, weight, and body mass index (BMI) were determined.

Expected Results: Prevalence of kidney damage markers in general population and risk groups; relationship in population between CKD and cardio-cerebral vascular disease, diabetes mellitus, hypertension, and other risk factors; comparison of Cockcroft-Gault and Modification of Diet in Renal Disease (MDRD) formulas for measuring the GFR and their application to studies involving mass population screenings; and stratification of CKD in population.

Conclusions: ISYS Phase I, active screening of markers for renal damage was concluded using the methodology described above; results are pending publication. (Abstract)