30
Trapianto Renale in Incompatibilita’ AB0 U.O.C. Trapianti Rene e Pancreas Direttore: Prof. Paolo Rigotti Azienda Ospedale Università di Padova Lucrezia Furian
Trapianto Renalein Incompatibilita’ AB0
U.O.C. Trapianti Rene e PancreasDirettore: Prof. Paolo Rigotti
Azienda Ospedale Università di Padova
Lucrezia Furian
Graft survivalDeceased vs Living Donor
Meier-Kriesche HU, Kaplan B. Transplantation 2002, 74 (10):1377-1381
Deceased donors Living donors
1448 1470 1487
17461671 1667
15851533
1650
1512 15421589
15011587 1580
134 126 142 145 116 108 112 137 152191 214 192 227 251
301
0
200
400
600
800
1000
1200
1400
1600
1800
2000
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Trapianti di rene da donatore vivente in Italia 2001-2015
Fonte SIT: Sistema informativo trapianti
Trapianti di rene da donatore deceduto r
Trapianti di rene da donatore vivente r
Trapianto di rene AB0 incompatibileMILESTONES
1989
MMF replaced
Azathioprine
Basiliximab
First AB0i tx in
Japan:
-Splenectomy
-Plasmapheresis
- Azathioprine
- Cyclosporine
- Steroids
2001 20042002
RITUXIMAB
replaced
splenectomy
1982-1987
AB0i tx in Belgium:
- Platelets donor transfusion
- - Plasmapheresis
- Splenectomy
- Cyclosporine
- Azathioprine
- Policlonal Ab
1987
Immunoadsorption
2005
Il trapianto di rene AB0 incompatibile: l’esperienza internazionale
Takahashia K et al., AJT:2004; 4: 1089–1096
Christopher J. Sonnenday C.J. et al., AJT: 2004; 4: 1315–1322
Tyden G et al., AJT: 2005; 5: 145–148
Aikawa A. et al.; Exp Clin Transplant 2015 Suppl 1: 18-22
Graft Survival 1989-2000 compared with 2001-2012 Graft Survival according to IgG titer (2001-2012)
AB0 Incompatibile Kidney Transplant:LONG TERMS RESULTS
738 AB0i KTfrom 280 Transplant Centres
Graft survival:
94.1% 1 year
89.6% 3 years
82.6% 5 years
72.9% 10 years
AB0 Incompatibile Kidney Transplant:LONG TERMS RESULTS
Transplantation 2007;83:1153
AB0 Incompatibile Kidney Transplant:LONG TERMS RESULTS
Trapianto di rene AB0 incompatibileMILESTONES
1989
MMF replaced
Azathioprine
First AB0i tx in Italy
Basiliximab
First AB0i tx in
Japan:
- Splenectomy
- Azathioprine
- Cyclosporine
- Steroids
2001 2004 2008 20102002
RITUXIMAB
replaced
splenectomy
First AB0i tx in
Padova
1982-1987
AB0i tx in Belgium:
- Platelets donor transfusion
- - Plasmapheresis
- Splenectomy
- Cyclosporine
- Azathioprine
- Policlonal Ab
1987
Immunoadsorption
2005
AB0 incompatible Kidney transplant: The italian experience
PARMA: Rituximab+Immunoadsorption+IVIG
PADOVA: Rituximab+Plasmapheresis+CMV-IgG
PISA: Rituximab+Plasmapheresis+IVIG
Kidney and Pancreas Transplantation Unit
University of Padua
July 2010 – November 2016
50 AB0i Living Donor
Transplants
0
10
20
30
40
50
60
4.7%
14%
16%32%
TOTALE TX ABOi= 50 26.1%
47.3%
AB0 COMPATIBILI AB0 INCOMPATIBILI
U.O.C. TRAPIANTI RENE E PANCREASTRAPIANTO DI RENE ABO INCOMPATIBILE: LA NOSTRA ESPERIENZA
Differences between these protocolsinclude: timing and dosage of rituximab induction therapies and continuous
immunosuppression isohaemagglutinin reduction techniques surveillance kidney graft biopsy
Transpl Int: 2015 Apr;28(4):387-97
Montgomery RA et al. Transplantation • Volume 87, Number 8, April 27, 2009
14 PTS 15 PTS 28 PTS
Guy’s Hospital minimal desensitization strategy
Transpl Int 2014 Feb;27(2):187-96
Transpl Int 2014 Feb;27(2):187-96
Kaplan–Meier survival curve of death-censored allograft survival at 3 years post-transplant.
Kaplan–Meier survival curve of rejection-free survival 1 year post-transplant.
Transpl Int 2014 Feb;27(2):187-96
Renal function of ABOi and ABOc transplant recipients
the minimum ‘safe’ antibody titer has not been defined
there is a wide range of assay techniques available for measuring antibodytiters
there is no international standardization of laboratories measuring anti-A oranti-B antibodies with wide
there is debate on which immunoglobulin subclass is the potential culpritleading to hyperacute rejection
the A1 and B antigens show more intense expression in kidney than A2, withimplications for a potentially higher risk of acute rejection in certain donor–recipient constellations
the clinical relevance of rebounding titers in the first weeks or even months oryears after transplantation is unknown
Il trapianto di rene AB0 incompatibile: ………. main issues
Böger CA et al.; Transpl Int. 2015 Mar;28(3):281-3
No significant differences in graft function at 3 months, 6 months, 1 year, 3 years,5 years or 10 years between the two groups
No significant statistical differences in patient and graft survival rates between the two groups
No significant difference in any type of graft rejectionTranspl Int 2015 Mar;28(3):286-96
Il trapianto di rene AB0 incompatibile: le biopsie di protocollo
Haas et al. AJT 2006; 6: 1829–1840
In biopsies of ABO-incompatible renalallografts C4d deposition in the absence ofhistologic evidence of rejection is a commonfinding, is not associated with an increasedrisk of graft scarring
The significance of such C4d staining remainsa topic of debate, and this finding may havedifferent implications in ABO-incompatibleversus conventional renal allografts.
Hass M.; Curr Opin Organ Transplant. 2010 Feb;15(1):21-7
Protocollo di
desensibilizzazione
-30 -6 -4 -2 +2 +4 +6
Rituximab 375 mg/m2
1^PP+CMVIgG3^PP+CMVIgG
2^PP+CMVIgG
1^PP+CMVIgG
2^PP+CMVIgG
3^PP+CMVIgG
Basiliximab
ATG
Monitoraggio isoemoagglutinine
pre e post plasmaferesi
0
TAC+MMF
TX
Protocollo di desensibilizzazione
U.O.C. TRAPIANTI RENE E PANCREASTRAPIANTO DI RENE ABO INCOMPATIBILE: LA NOSTRA ESPERIENZA
ABOi renal transplant recipients – initial (predesensitization) anti-A/B antibody titres
KIDNEY AND PANCREAS TRASPLANTATION UNIT-PADUAAB0 INCOMPATIBLE KIDNEY TRANSPLANT: OUR EXPERIENCE
0
2
4
6
8
10
12
1 2 4 8 16 32 64 128 256
Determination and monitoring of anti-AB0 antibody titers
Microcolumn agglutination technique(GEL CARD DIA-MED)
7 patients with DSA MFI:1000-5400
ABOi renal transplant recipients anti-A/B antibody titres at tranpslant
Nu
mb
er
KIDNEY AND PANCREAS TRASPLANTATION UNIT-PADUAAB0 INCOMPATIBLE KIDNEY TRANSPLANT: OUR EXPERIENCE
0
2
4
6
8
10
12
Initial antibodytitres
<16
PP pre+CMV IgG
No PP post-TX
≥16
Rituximab
Transplant: Basiliximab/Thymoglobuline and steroidsMaintenance immunosuppressive therapy: Tacrolimus e MMF
MONITORING OF ANTI-ABO ANTIBODY TITERS BEFORE AND AFTER TRANSPLANTION
KIDNEY AND PANCREAS TRASPLANTATION UNIT-PADUAAB0 INCOMPATIBLE KIDNEY TRANSPLANT: OUR EXPERIENCE
Desensitization Protocol
KIDNEY AND PANCREAS TRASPLANTATION UNIT-PADUAAB0 INCOMPATIBLE KIDNEY TRANSPLANT: OUR EXPERIENCE
Pazienti
Rituximab, PP before and after transplant + CMVIgG/IgVena 24
No Rituximab, PP before and after transplant + CMV IgG 1
Rituximab alone 3
Rituximab, PP+CMV IgG before transplant, PP post-trasplant on demand 17
Rituximab, Therasorb+CMV IgG before and after Tx 3
Rituximab, Glycosorb+CMV IgG before Tx 2
MONITORING OF ANTI-ABO ANTIBODY TITERS BEFORE AND AFTER TRANSPLANTION
NO MORE PROTOCOL BIOPSIES
Results
KIDNEY AND PANCREAS TRASPLANTATION UNIT-PADUAAB0 INCOMPATIBLE KIDNEY TRANSPLANT: OUR EXPERIENCE
ABO incompatible AB0 compatible
Patients 50 145
Follow-up (median) (DS) 12 (10.4±13) 26 (28±18.4)
Death
Graft loss
1
1
0
1
DGF
Duration of DGF (days)
0
0
1
6
PNF 0 0
Patients treated for acute rejection (%) 7 (10%) 13 (8.9%)
Trasfusions
N° patients (%) 10 (20%) 17 (14.9%)
Lenght of hospital stay (days) 15 (13-16) 12 (11-14)
0
20
40
60
80
100
120
140
DIMISSIONE 1 MESE 3 MESI 6 MESI
Cre
atin
ine
mia
µm
ol/
L
50
55
60
65
70
1 MESE 3 MESI 6 MESI
Cle
aran
ced
ella
cr
eat
inin
a m
l/m
in
AB0 INCOMPATIBILI AB0 COMPATIBILI
Renal Function
KIDNEY AND PANCREAS TRASPLANTATION UNIT-PADUAAB0 INCOMPATIBLE KIDNEY TRANSPLANT: OUR EXPERIENCE
Complications
KIDNEY AND PANCREAS TRASPLANTATION UNIT-PADUAAB0 INCOMPATIBLE KIDNEY TRANSPLANT: OUR EXPERIENCE
AB0 incompatible AB0 compatible p-value
Patients 50 145
SURGICALSBleedingHematomaLymphoceleWound dehiscenceBowel obstruction
1 (2%)01 (2%)00
1 (0.68%)1 (0.68%)1 (0.68%)1 (0.68%)1 (0.68%)
-----
INFECTIONSCMVBKPyelonephritisPneumoniaCellulite
3 (6%)1 (2%)
00
1 (2%)
6 (4.13%)3 (2.06%)2 (1.37%)1 (0.68%)1 (0.68%)
0.620.54
--
0.30
MEDICAL
PTDM
LeukopeniaPTLD
02 (4%)
0
6 (4.13 %)3 (2.06%)1 (0.68%)
0.580.20
-
CONCLUSIONI
I RISULTATI OTTENUTI DAI TRAPIANTI DI RENE DA DONATOREVIVENTE AB0 INCOMPATIBILE SONO OTTIMI E PARAGONABILI AQUELLI OTTENUTI NEI TRAPIANTI DI RENE DA DONATORE VIVENTEAB0 COMPATIBILE
IL PROTOCOLLO DI DESENSIBILIZZAZIONE BASATO SU RITUXIMAB,PLASMAFERESI E CMV-IgG SPECIFICHE SI È DIMOSTRATO EFFICACEE SICURO
LA TENDENZA GENERALE SEMBRA UNA RIDUZIONE DEIPROTOCOLLI DI DESENSIBILIZZAZIONE
IL PROGRAMMA DI TRAPIANTO AB0 INCOMPATIBILE HAPERMESSO DI AUMENTARE IL NUMERO DI TRAPIANTI DADONATORE VIVENTE
U.O.C. TRAPIANTI RENE E PANCREAS - Azienda Ospedale Università di Padova
Paolo Rigotti, Cristina Silvestre, Flavia Neri
U.O.C IMMUNOTRASFUSIONALE - Azienda Ospedale Università di Padova
Giustina De Silvestro, Piero Marson, Tiziana Tison, Anna Colpo
IMMUNOLOGIA DEI TRAPIANTI- Azienda Ospedaliera di Padova
Emanuele Cozzi, Michela Seveso, Elena Ruffoni
ISTITUTO DI ANATOMIA PATOLOGICA-CLOPD - Azienda Ospedale Università di Padova
Marialuisa Valente
U.O. NEFROLOGIA I e NEFROLOGIA II - Azienda Ospedale Università di Padova
Luciana Bonfante, Barbara Rossi, Francesco Marchini
U.O. NEFROLOGIA E DIALISI - Spedali Civili di Brescia
Silvio Sandrini, Francesca Valerio
RINGRAZIAMENTI
