Resumen

AZURMENDI, Pablo et al. Glomerular filtration rate decline in autosomic dominant polycystic kidney disease. Influence of endothelial NO synthase (ecNOS) and renin angiotensin system gene polymorphisms. Medicina (B. Aires) [online]. 2004, vol.64, n.2, pp. 139-142. ISSN 1669-9106.

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 (£ and > 55 years). In £ 55 (assumed as PKD1 phenotype) (n=42), A₂ and A₆ of the AT11166CC 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.

Palabras llave : GFR decline; ADPKD; AT1A1166C; AGTM235T; ecNOSGlu298Asp.