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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Chronic Kidney Disease in Children and Adolescents in Salvadoran Farming Communities: NefroSalva Pediatric Study (2009–2011)
January–April 2016, Vol 18, No 1–2

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:

Variable (n)

CKD status

No CKD

Stage 1

Stage 2

Stages 3–5
n (stage)

Total
with CKD

Total (1623)
n
1560
56
5
1(3a) + 1(5)
63
%
96.1
3.5
0.3
0.1
3.9
95% CI
95.2–97.1
2.6–4.3
0.0–0.6
0.0–0.3
2.9–4.8
Age 2–5 years
(312)
n
296
14
2
0
16
%
94.9
4.5
0.6
 
5.1
95% CI
92.4–97.3
2.2–6.8
0.0–1.5
2.7–7.6
6–12 years
(756)
n
728
26
1
1(5)
28
%
96.3
3.4
0.1
0.1
3.7
95% CI
94.9–97.6
2.1–4.7
0.0–0.4
0.0–0.4
2.4–5.1
13–17 years
(555)
n
536
16
2
1(3a)
19
%
96.6
2.9
0.4
0.2
3.4
95% CI
95.1–98.1
1.5–4.3
0.0–0.9
0.0–0.5
1.9–4.9
Sex Male
(800)
n
771
23
5
1(3a)
29
%
96.4
2.9
0.6
0.1
3.6
95% CI
95.1–97.7
1.7–4.0
0.1–1.2
0.0–0.4
2.3–4.9
Female
(823)
n
789
33
0
1(5)
34
%
95.9
4.0
 
0.1
4.1
95% CI
94.5–97.2
2.7–5.4
0.0–0.4
2.8–5.5
Region Bajo Lempa
(866)
n
831
31
4
0
35
%
96.0
3.6
0.5
 
4.0
95% CI
94.6–97.3
2.3–4.8
0.0–0.9
2.7–5.4
Guayapa Abajo
(412)
n
399
10
1
1(3a) + 1(5)
13
%
96.8
2.4
0.2
0.5
3.2
95% CI
95.2–98.5
0.9–3.9
0.0–0.7
0.0–1.2
1.5–4.8
Las Brisas
(345)
n
330
15
0
0
15
%
95.7
4.3
 
 
4.3
95% CI
93.5–97.8
2.2–6.5
2.2–6.5
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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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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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