ABSTRACT 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.

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%), β2 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.

INTRODUCTION: Chronic kidney disease is a global pandemic, affecting the majority of countries in the world. Its prevalence is approximately 10% and it is associated mainly with diabetes and high blood pressure. In El Salvador, it is the leading cause of hospital deaths among men. OBJECTIVE: Determine prevalence of chronic kidney disease and its risk factors in two Salvadoran farming communities. METHODS: From March through September 2012, a descriptive cross-sectional study was conducted in two Salvadoran farming communities: Dimas Rodríguez (El Paisnal municipality) and El Jícaro (San Agustín municipality). The research involved both epidemiological and clinical methods. An active search for chronic kidney disease and its risk factors was carried out in the population aged >15 years. House-to-house visits were carried out to take family and individual health histories and gather data on social conditions and risk factors. A physical examination was performed, along with laboratory tests (urinalysis and blood chemistry) to measure renal function and detect markers for renal damage. RESULTS: A total of 223 persons of both sexes were studied. Overall prevalence of chronic kidney disease was 50.2%. Prevalence of chronic renal failure was 16.1%, with slight variations between the sexes. In El Jícaro, 77.3% of participants reported contact with agrochemicals and 76.6% were farmworkers; the respective figures for Dimas Rodríguez were 75.8% and 73.7%. The next most frequently reported risk factor was NSAID use, at 61.7% in El Jícaro and 77.9% in Dimas Rodríguez. CONCLUSIONS: CKD prevalence is alarming in these communities, among both young and old, men and women, independently of occupation. Health services must cope with the increased CKD burden observed, and are challenged to implement preventive strategies.

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.

The role of sympathetic nerve activity in the changes in arterial blood pressure and renal function caused by the chronic administration of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, was examined in sham and bilaterally renal denervated rats. Several studies have demonstrated that sympathetic nerve activity is elevated acutely after L-NAME administration. To evaluate the role of renal nerve activity in L-NAME-induced hypertension, we compared the blood pressure response in four groups (N = 10 each) of male Wistar-Hannover rats weighing 200 to 250 g: 1) sham-operated vehicle-treated, 2) sham-operated L-NAME-treated, 3) denervated vehicle-treated, and 4) denervated L-NAME-treated rats. After renal denervation or sham surgery, one control week was followed by three weeks of oral administration of L-NAME by gavage. Arterial pressure was measured weekly in conscious rats by a tail-cuff method and renal function tests were performed in individual metabolic cages 0, 7, 14 and 21 days after the beginning of L-NAME administration. L-NAME (60 mg kg-1 day-1) progressively increased arterial pressure from 108 ± 6.0 to 149 ± 12 mmHg (P<0.05) in the sham-operated group by the third week of treatment which was accompanied by a fall in creatinine clearance from 336 ± 18 to 222 ± 59 µl min-1 100 g body weight-1 (P<0.05) and a rise in fractional urinary sodium excretion from 0.2 ± 0.04 to 1.62 ± 0.35% (P<0.05) and in sodium post-proximal fractional excretion from 0.54 ± 0.09 to 4.7 ± 0.86% (P<0.05). The development of hypertension was significantly delayed and attenuated in denervated L-NAME-treated rats. This was accompanied by a striking additional increase in fractional renal sodium and potassium excretion from 0.2 ± 0.04 to 4.5 ± 1.6% and from 0.1 ± 0.015 to 1.21 ± 0.37%, respectively, and an enhanced post-proximal sodium excretion compared to the sham-operated group. These differences occurred despite an unchanged creatinine clearance and Na+ filtered load. These results suggest that bilateral renal denervation delayed and attenuated the L-NAME-induced hypertension by promoting an additional decrease in tubule sodium reabsorption in the post-proximal segments of nephrons. Much of the hypertension caused by chronic NO synthesis inhibition is thus dependent on renal nerve activity.