Tubular epithelial cell and podocyte apoptosis with de novo sirolimus based immunosuppression in renal allograft recipients with DGF

R Munivenkatappa, A Haririan… - Histology and …, 2010 - digitum.um.es
R Munivenkatappa, A Haririan, JC Papadimitriou, CB Drachenberg, M Dinits-Pensy…
Histology and histopathology, 2010digitum.um.es
Sirolimus is associated with prolongeddelayed graft function (DGF) following
renaltransplantation and exacerbation of proteinuria. Weassessed renal allograft biopsies
from DGF patientstreated with de novosirolimus (n= 10) for renal tubularcell and podocyte
apoptosis and expression of activatedcaspase-3, Bcl-2, and mTOR and compared them
tobiopsies from DGF patients not receiving sirolimus (n= 15). Both groups received
mycophenolate mofetil, prednisone and antibody induction. Apoptosis wasassessed using …
Sirolimus is associated with prolongeddelayed graft function (DGF) following renaltransplantation and exacerbation of proteinuria. Weassessed renal allograft biopsies from DGF patientstreated with de novosirolimus (n = 10) for renal tubularcell and podocyte apoptosis and expression of activatedcaspase-3, Bcl-2, and mTOR and compared them tobiopsies from DGF patients not receiving sirolimus (n =15). Both groups received mycophenolate mofetil,prednisone and antibody induction. Apoptosis wasassessed using terminal deoxynucleodidyl transferasemediated dUTP nick end labeling (TUNEL) staining.Caspase-3, Bcl-2, and mTOR expression were assessedby immunohistochemistry. Sirolimus treated patients had334±69 TUNEL positive cells per 5 high power fieldscompared to 5.5±2.9 TUNEL positive cells in controlpatients (p<0.001). The number of TUNEL positive cellscorrelated with tubular architectural disruption.Expression of activated caspase-3, Bcl-2, or activatedmTOR did not differ between groups. 60% of biopsiesfrom sirolimus treated patients compared to 7% ofbiopsies from controls showed diffuse podocyteapoptosis (p = 0.007). There was no podocyte expressionof activated mTOR, activated caspase-3, or Bcl-2 ineither group. These data suggest that DGF patientstreated with sirolimus have increased renal tubular cellapoptosis and podocyte apoptosis.
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