title: [Progression of autosomic dominant polycystic kidney disease. Influence of endothelial NO synthase (ecNOS) and renin angiotensin system gene polymorphisms].
abstract: Glomerular filtration rate decline (GFRd) is variable in autosomic dominant polycystic kidney disease (ADPKD). In 88 ADPKD patients, GFRd was assessed by 1/S(Cr) and compared with the association to AT1A1166C (AT1R), AGTM235T (angiotensinogen) and ecNOSGlu298Asp (NO endothelial synthase) polymorphisms. Age at S(Cr) values of 2 and 6 mg/dl were assumed as beginning of progressive phase (A2) and end-stage-renal disease (A6), respectively. Polymorphisms were studied by PCR-RFLP. The group as a whole showed GFRd (ml/min/year) of 6.9+/-0.5; A2 and A6 of 48.9+/-1.3 and 55.0+/-1.4 years and mean arterial pressure of 111.2+/-1.2 mmHg. When A6 was considered, two populations were defined (< or = and > 55 years). In < or = 55 (assumed as PKD1 phenotype) (n=42), A2 and A6 of the AT1 1166CC genotype were 36.0+/-1.2 and 41.4+/-0.9 years vs AA-AC (42.8+/-1.0 and 47.5+/-0.8, p<0.001). A2 and A6 of the ecNOS298Asp/Asp genotype were 34.8+/-1.5 and 41.1+/-0.6 years vs. Glu/Glu-Glu/Asp (42.4+/-0.9 and 47.1+/-0.8, p<0.02). In AGT235TT genotype, GFRd was 12.4+/-2.2 ml/min/year vs MM-MT (7.9+/-0.7, p<0.03). This difference was also observed when all ADPKD patients were considered (TT: 11.02+/-1.5 vs. MM-MT: 6.44+/-0.5 ml/ min/year, p<0.003). AT1 1166CC and ecNOS 298Asp/Asp are associated with earlier A2 and A6 whereas AGT 235TT induce twofold increase in GFRd, suggesting that RAS and ecNOS are involved in ADPKD progression.
authors.affiliation: Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
authors.forename: Pablo
authors.initials: P
authors.lastname: Azurmendi
authors.forename: Adriana
authors.initials: A
authors.lastname: Fraga
authors.forename: Carolina
authors.initials: C
authors.lastname: Muchnik
authors.forename: Maria
authors.initials: M
authors.lastname: Dos Ramos Farias
authors.forename: Felicita
authors.initials: F
authors.lastname: Galan
authors.forename: Danisa
authors.initials: D
authors.lastname: Guerra
authors.forename: Martin
authors.initials: M
authors.lastname: O'Flaherty
authors.forename: Elvira
authors.initials: E
authors.lastname: Arrizurieta
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Martin
mesh_terms: D000328:Adult; D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D018450:Disease Progression; D005838:Genotype; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008875:Middle Aged; D009569:Nitric Oxide / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012084:Renin-Angiotensin System / Q000235:genetics*
chemical_list: D000808:Angiotensinogen; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse