IFIBIO HOUSSAY   25014
INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Characterization of chronic nephropathy in rats surviving Hemolytic Uremic Syndrome
Autor/es:
MELENDI, S; CHIQUILITO, F; SEYAHIAN, E. A; ARAOZ, A; LAGO, N; OCHOA, F; ZOTTA, E
Lugar:
Boston
Reunión:
Congreso; 9th Triennial International Symposium on Shiga Toxin Producing Escherichia coli Infections; 2015
Resumen:
Introduction: Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy associated with Shiga Toxin (Stx) producing Escherichia coli (STEC). Its clinical features are non-immune mechanical hemolytic anemia, thrombocytopenia and organ dysfunction with particular renal tropism. HUS is a frequent cause of renal insufficiency in children, Four years after an episode,3% of children develop end-stage renal disease and 25% suffer from reduced renal function1. Our aim is to characterize the physiopathology factors related with evolution of renal injury to chronicity in a HUS model in rats.Methods: Adult male Sprague-Dawley rats (200g) were randomly divided into two groups and injected intraperitoneally with culture supernatant of recombinant E. coli expressing Stx2 (Experimental group) or not (Control group), A random half of experimental group received enalapril in water while other half received no medications. Dose of Stx2 administered was previously assessed using Kaplan-Meier curve to allow survival after HUS. Rats were sacrificed at 1 week and 12 weeks and functional, histological, immunohistochemical and molecular studies were performed in all groups. Results and Discussion: The functional studies performed show a decreased GFR and increased EFNa at 1 week with no significant variation at 12 weeks while proteinuria and microalbuminuria are increased at 12 weeks. Our histological findings display a significant cortex and medulla fibrosis at both time points with a remarkable alteration of arteriolar walls, this histological findings correlate with immunohistochemical stain for AgII and TGF-β, both augmented which different patrons at 1 and 12 weeks. The enalapril treated ratsdemonstrated significant changes in proteinuria, fibrosis and arteriolar modifications. Implications: Our results show that profibrotic mediators such as AgII and TGF-β have a central role in physiopathology of chronic nephropathy in rats that survive HUS.