Rol de la angiogénesis en la progresión a Nefropatía Crónica del Injerto: Fibrosis Intersticial/Atrofica Tubular
Palavras-chave:
angiogénesis, disfunción crónica del injerto, orina, marcador no invasivo, predicciónResumo
Fundamento: La Disfunción Crónica del Aloinjerto (CAD) es la causa más prevalente de pérdida tardía de injertos renales. Los cambios estructurales asociados con CAD (fibrosis intersticial/atrofia tubular, IF/TA) contribuyen a la mantención de un estado hipóxico, fundamental para la iniciación de la angiogénesis. Resultó de interés investigar el estado quiescente o angiogénico presente en CAD. El perfil de ARNm celular urinario puede contribuir a detectar y predecir el daño temprano post-trasplante. Pacientes: Se estudiaron 140 pacientes trasplantados renales (PTR) de quienes se obtuvieron biopsias que fueron clasificadas según los criterios Banff en Necrosis Tubular Aguda (NTA), n=48; Rechazo Celular Agudo (RCA), n=27; IF/TA, n=32. Aloinjertos normales (AN, n=33) fueron el grupo control. Se recolectaron orinas (n=34) a t=1, 3, 6, 9, 12 y 24 meses post-trasplante. Se agruparon los PTR según índice de filtrado glomerular estimado (eGFR) a t=12 meses en: No Progresores (NP, n=14, eGFR > 45 ml/min) y Progresores (P, n = 20, eGFR < 45 ml/min). Once muestras apareadas (biopsia/orina) se utilizaron para evaluar su correlación. Los niveles de expresión génica de ANG1, ANG2, PDGF, VEGF, END, TSP-1, VCAM-1, SEL-E, EGFR, TGF-?, FGF y HGF se cuantificaron utilizando PCR en Tiempo Real. Los análisis se realizaron utilizando Test T-Student, ANOVA, correlación de Pearson y regresión lineal y logística. Resultados: Se obtuvieron niveles significativamente aumentados para FGF (p=0,0003), PDGF (p=0,0005) y TGF-? (0,0002), mientras que VEGF (p<0,0001), SEL-E (p<0,0001), ANG1 (p<0,0001), ANG2 (p<0,0001) se hallaron disminuidos en IF/TA, comparado con AN. No se encontraron diferencias con los otros grupos histológicos. La correlación de muestras apareadas mostró para VEGF, R² Aj = 0,77 (p=0,003) y TSP-1, R² Aj = 0,88 (p<0,001). En las orinas a t=3meses se encontraron TGF-? y PDGF incrementados en P (p < 0,0001 en ambos casos) y VEGF disminuido (p=0,0235). El modelo de regresión logística múltiple mostró que las variables PDGF y TGF-? a t=3 meses tienen la capacidad de predecir pronóstico (sensibilidad 100%, especificidad 93%). Conclusiones: La angiogénesis es un mecanismo crítico en la progresión a CAD. La expresión temprana de determinados genes predice el curso del riñón trasplantado.Downloads
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