PIG KIDNEY TRANSPLANTATION IN BABOONS.  OUR EXPERIENCE IN 20 CASES.

 

Mosquera Reboredo Juan M.1; Vázquez Martul E. 1; Mánez R.2; Alonso Hernández, Angel L.3; Gonzalez Martin M.4

 

Departament of Pathology1, Transplant Coodination Office2, Nefrologia3 and Departament of Urology4 of "Juan Canalejo Hospital". A Corunia. Spain

 

Introduction:

Renal xenotransplantation of pig organs is the best hope to alleviate the shortage of cadaveric organ donors for transplantation. However, the humoral rejection that pig organs undergo in non-human primates have prevented the clinical application of xenotransplantion. Here, we report our experience in the xenotransplantation of pig kidneys transgenic for human DAF (hDAF) in baboons.

 

Methods:

From November 2000 to June 2002 20 baboons underwent a renal transplantation with hDAF pig organs, in a functional model (nephrectomy of native kidneys). Four protocols of immunosuppression were used: Cyclophosphamide (CyP) + Cyclosporine (CyA)+ERL(n=ll); CyP+FTY 720+ CyA (n=2); Baxiliximab+ FTY720+ CyA (n=3); Baxiliximab + FTY 720+ Everolimus (n=4). Xenograft tissue samples were obtained before reperfusion, If2 hour after reperfusion and at xenograft failure, embedded in parafin and stained with H/E, PAS and Masson trichrome. Snap-cooled tissue samples were also obtained for immunohistochemestry (IgG ,IgM, C3, C4 and C5b9) and/or immunofluorescence (IgG, IgM, IgA, C3, and C4) analysis.

 

Results:

Xenograft survival ranged from I to 31 days. Nine hDAF pig kidneys (45%) failed between 8 and 20 days because acute humoral rejection (AHR), showing thrombotic microangiophaty , congestion, interstitial hemorrhage or necrosis and deposits of IgM and complement (C5b9, C4) (by immunohistochemistry and/or immunofluorescence) in both peritubular and glomerular capillaries or only in glomerulali. Seven xenografts (35%) failed within one of transplantation and the pathology showed unspecific histologic changes of acute tubular necrosis (ATN) with or without peritubular congestion and lack of antibodies and complement deposits. The other four xenografts failed because venous thrombosis (day 1), surgical hemorrhage (day 1), ureteral obstruction (day 31) and CMV sepsis (day 28). The four immunosuppression protocols used were associated with a similar frequency of xenografts failing from AHXR or other causes.

 

Conclusions:

AHXR is the main cause of xenograft failure in hDAF pig to baboon renal transplantation. However, a third of the xenografts failed within one week of transplantation from A TN resulting from unknown causes. Along with new strategies to prevent AHXR, improvement of hDAF pig requires a better understanding of the non-immunologic factors leading to ATN early after transplantation.

 

 

PIG KIDNEY TRANSPLANTATION IN BABOONS.  OUR EXPERIENCE IN 20 CASES.

 

Mosquera Reboredo Juan M.1; Vázquez Martul E. 1; Mánez R.2; Alonso Hernández, Angel L.3; Gonzalez Martin M.4

 

Departament of Pathology1, Transplant Coodination Office2, Nefrologia3 and Departament of Urology4 of "Juan Canalejo Hospital". A Corunia. Spain

 

Mosquera Reboredo Juan Manuel

Direccion correo:

Hospital Juan Canalejo. Servicio de Anatomia Patologica

As Xubias, 84

15006 A Coruna

Email:  jmmosquera@cnio.es

           jmosquerareboredo@jahoo.es