RESUMO
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.
La velocidad de progresión (VdP) de la poliquistosis renal autosómica dominante (PQRAD) es variable.Estudiamos la asociación de los polimorfismos AGTM235T (angiotensinógeno), AT1A1166C(ATR1) y ecNOSGlu298Asp (NO sintasa endotelial) con la VdP en 88 pacientes. VdP fue estimada por 1/Crplvs edad. Consideramos edades de Crpl 2 y 6 mg/dl como comienzo de progresión (E2) y arribo a insuficienciarenal crónica terminal (E6), respectivamente. Los polimorfismos se estudiaron por PCR-RFLP. El grupo en sutotalidad presentó VdP (ml/min/año) de 6.9±0.5, E2 y E6 de 48.9±1.3 y 55.0±1.4 años y tensión arterial media(TAM) de 111.2±1.2 mmHg. Según E6 observamos dos grupos (≤ y > a 55 años). En ≤ 55 (fenotipo PKD1,n=42), E2 y E6 del genotipo CC de AT1A1166C fueron 36.0±1.2 y 41.4±0.9 años vs. AA-AC (42.8±1.0 y 47.5±0.8, p < 0.001). E2 y E6 del genotipo ecNOS298Asp/Asp fueron 34.8±1.5 y 41.1±0.6 años vs. Glu/Glu-Glu/Asp (42.4±0.9 y 47.1±0.8, p < 0.02). En el genotipo AGT235TT, la VdP fue 12.4±2.2 ml/min/año vs. MM-MT (7.9±0.7, p < 0.03). Esta diferencia también se observó cuando analizamos todos los pacientes PQRAD (TT: 11.02±1.5 vs. MM-MT: 6.44±0.5 ml/min/año, p < 0.003). Los genotipos AT1 1166CC y ecNOS 298Asp/Asp anticipan E2 y E6 mientras que AGT235TT duplica VdP, sugiriendo la participación del sistema renina angiotensina y NO sintasaendotelial en la progresión de la PQRAD.
Assuntos
Adulto , Animais , Humanos , Camundongos , Pessoa de Meia-Idade , Angiotensinogênio/genética , Falência Renal Crônica/genética , Óxido Nítrico Sintase/genética , Polimorfismo Genético , Rim Policístico Autossômico Dominante/genética , Sistema Renina-Angiotensina/genética , Progressão da Doença , Falência Renal Crônica/patologia , Genótipo , Taxa de Filtração Glomerular , Óxido Nítrico Sintase Tipo II , Óxido Nítrico Sintase Tipo III , Óxido Nítrico/genética , Fenótipo , Análise de Regressão , Rim Policístico Autossômico Dominante/patologiaRESUMO
The effects of acute renal failure on the impeded (IER) and unimpeded (UER) eruption dental rate and attrition rate (AR) were investigated. Adult female Wistar rats were injected with 125 mg/kg b.w of human methemoglobin (M-Hb) in order to induce a first episode of hemodynamically-mediated acute renal failure (H-ARF). Ten days after the injection of M-Hb, other groups of rats received another equal dose of the drug in order to induce a second episode of H-ARF. A group of six animals was pair-fed daily and individually with rats of M-Hb groups. Evaluation of renal function, histopathology studies, IER, UER, food intake (FI), AR and body weight gains was performed at different times after the first and second injections, of M-Hb. Treatment induced transient increases in plasma urea concentration and urine volume, and significant depression in urine osmolality, body weight gains, IER, UER and AR. In every case, the maximal effect of the first injection of M-Hb on the individual parameters was always greater than that of the second injection. Histologic sections showed interstitial cellular infiltration, desquamation of the proximal tubular epithelium and collapse or dilation of the tubular lumen. The functional values of kidney, histologic findings, IER, UER and AR of the pair-fed rats were not significantly different from control values. The results of the present study indicate that dental eruption rate (IER and UER) is relatively low in uremic rats with kidney tubule lesions and that both parameters are related.