title: Renin-angiotensin system polymorphisms and renal scarring.
abstract: The purpose of the study was to determine whether DNA polymorphisms at the renin-angiotensin-aldosterone (RAS) genes were associated with evolution to renal scar formation and, consequently, with reflux nephropathy (RN) in patients with vesicoureteral reflux (VUR). Some authors have suggested that the DD genotype of the angiotensin-converting enzyme (ACE) gene would be an adverse renal prognosis factor. We recruited 246 patients (aged 3 months to 22 years) from four Spanish hospitals. These included 69 patients with VUR, 110 with RN (determined by absence/presence of renal scarring on dimercaptosuccinc acid scan), 27 with chronic renal failure due to RN, and 40 patients (control group) with urinary tract infection and normal findings on renal ultrasonography and voiding cystoureterogram. The ACE I/D, angiotensin II type 1 receptor AT1 A1166C, angiotensin II type 2 receptor A3123C AT2, and angiotensinogen AGT M235T polymorphisms were determined on the basis of polymerase chain reaction amplification. ACE serum levels were determined by spectrophotometric methods. We found no statistical differences in the distribution of RAS polymorphisms between the different groups. The ACE D allele was linked to higher ACE serum levels. We found no association between ACE I/D polymorphism and presence of hypertension, proteinuria, grade of VUR, or unilateral/bilateral VUR. Patients with the DD genotype had a lower incidence of febrile urinary tract infection as a first symptom of VUR/RN (P<0.05). We conclude that genetic polymorphisms of RAS components are not independent prognostic indicators of renal scarring in patients with VUR.
authors.affiliation: Department of Pediatric Nephrology, Hospital Central de Asturias, Oviedo, Asturias, Spain. rpardo@hcas.insalud.es
authors.forename: Rafael
authors.initials: R
authors.lastname: Pardo
authors.forename: Serafín
authors.initials: S
authors.lastname: Málaga
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.forename: Mercedes
authors.initials: M
authors.lastname: Navarro
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Laura
authors.initials: L
authors.lastname: Espinosa
authors.forename: Ruth
authors.initials: R
authors.lastname: Alvarez
authors.forename: Alfredo
authors.initials: A
authors.lastname: Vallo
authors.forename: Cesar
authors.initials: C
authors.lastname: Loris
authors.forename: Socorro
authors.initials: S
authors.lastname: Braga
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D007674:Kidney Diseases / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000235:genetics; D008297:Male; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D012084:Renin-Angiotensin System / Q000235:genetics*; D014552:Urinary Tract Infections / Q000235:genetics; D014718:Vesico-Ureteral Reflux / Q000235:genetics*
chemical_list: D007703:Peptidyl-Dipeptidase A