05 Trapianto renale Bergamo

Il trapianto renale a Bergamo
Eliana Gotti
1
23 Dicembre 1954, ore: 8.00
Ospedale Peter Bent Brigham di Boston
1
1.223,624 ORGAN TRANSPLANTS
PERFORMED WORLDWIDE UP TO 2009
Transplants n°
Kidney
Liver
Heart
Lung
Kidney/pancreas
Pancreas/Islet
Heart/lung
Intestine
873,538
194,419
87,823
30,095
24,093
8,243
4,476
937
Cecka et al., Clinical Transplants, 2010
Kidney transplantation
In patients with end stage renal disease
successful renal allotransplantation improves
the quality of life and increases survival as
compared with long-term dialysis treatment
1
Wolfe et al, N Engl J Med 1999
2
THE GAP BETWEEN KIDNEY TRANSPLANT
DEMAND AND SUPPLY
Waiting list*
US
Transplant*
Death
on
waiting list °
(n)
(n)
(n)
84,766
16,829
5,251
6,808
1,651
102
Italy
* By December 31, 2009. °During 2009
UNOS.org, 2010
CNT, 2010
5
CAUSE DI INSUFFICIENZA RENALE CRONICA
• Diabete mellito
24 %
• Glomerulonefriti
11.8 %
• Pielonefriti /reflusso
7.8 %
• Malattia Policistica dell’adulto
7.5 %
• Malattia renovascolare
6.9 %
• Ipertensione
6%
• Altre cause
15.6 %
• Diagnosi incerta
20.7 %
3
Controindicazioni relative a trapianto
• Età > 65
• Malattie cardiovascolari
• Obesità
• Infezione da HIV
• Pregressa neoplasia
• Epatite cronica B/C
Trapianto renale
- Da donatore: - cadavere
- vivente
- Trapianto di rene singolo / doppio
- Trapianto pre-emptive
4
Trapianto renale
1
THE IMMUNOSUPPRESSIVE ARMAMENTARIUM TO CONTROL GRAFT
1954
REJECTION
None
1960
Azathioprine
1965
Steroids
1970
Anti-T cell Abs
1980
Cyclosporine
1990
OKT3 mAb
1995-2005
Mizoribine
Deoxyspergualin
Tacrolimus
Mycophenolate mofetil/myfortic
Basiliximab/Daclizumab
Sirolimus/everolimus
FTY720
5
% 1-Year Graft Survival
100
80
60
Acute rejection (%)
40
CsA
55-60
ST + AZA ‘77
35-40
CsA + ST + AZA ‘83
20
0
75 76 77 78 79 80 81 82 83 84 85 86 87 88 89
90 91
Year of Transplant (1975-1990)
Gjertson et al., 1992
GRAFT SURVIVAL AFTER RENAL TRANSPLANTATION
IN THE PERIOD 1988-2004
30
Cadaver donor
20
13.8
(years)
Projected median half-life
Analysis of UNOS data on patients with functioning kidney 1 year post transplant
11
10
8
0
88
89
90
91
92
93
94
95
2004
years of transplant
Hariharan et al., N Eng J Med, 2000
OPTN website, 2009
1
6
THE MAINTENANCE IMMUNOSUPPRESSION
Maintenance immunosuppression is best achieved using
combination of immunosuppressive agents
Combination therapy aims to minimize the side-effects
of any single drug whilst targeting multiple steps in Tcell activation
Triple-drug regimen
Corticosteroids
Calcineurin
inhibitor
Antiproliferative
agent
CALCINEURIN INHIBITOR NEPHROTOXICITY IS VIRTUALLY
UNIVERSAL BY 10 YEARS AFTER TRANSPLANTATION
120 type 1 diabetic patients with kidney-pancreas transplant
CN-inhibitor nephrotoxicity
(%)
961 kidney transplant biopsy: Tx to 10 years thereafter
Triple-therapy immunosuppression: CsA or tacrolimus, Aza or MMF,
prednisolone
100
80
93.5
96.8
76.4
60
40
20
0
1 yr
5 yrs
Post-Tx
10 yrs
Nankivell et al., N Engl J Med, 2003
7
Corticosteroids and calcineurin inhibitors
are effective in reducing the incidence of
acute rejection, but are a major cause of
morbidity and mortality
As a result, a number of clinical trials
have examined whether steroids or
calcineurin inhibitors can be safely
withdrawn after renal transplantation
THE TARGET:
TRANSPLANTATION TOLERANCE
One of the major questions remaining in
clinical transplantation is whether it will be
possible to induce states of true tolerance with
little or no long-term drug therapy
…ideally one would like to alter the host’s
initial contact with the graft to promote a state
of donor-specific unresponsiveness
Carpenter, N Engl J Med, 1993
8
All treatment protocols were
approved by the Istituto Superiore
di Sanità (ISS, Rome, Italy,
Authorization n° 45253 (06)PRE.21-882)
and
by
the
Institutional Review Board of the
Ospedali
Riuniti
Bergamo
(Delibera n°352 – March 18, 2008)
Istituto Superiore di Sanità
Written informed consents were
obtained from all recipients and
living kidney donors
17
17
ATTIVITÀ DI TRAPIANTO DI RENE:
BERGAMO 1989-2010
1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000
1
14
29
30
31
39
37
36
44
42
36
35
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
43
40
37
37
36
43
44
33
41
28
43
31/12/2011 = 799
9
Attività di Trapianto a Bergamo
- Da donatore vivente: 29
- Doppio trapianto: 68
- Trapianto combinato
- cuore-rene: 5
- fegato-rene: 30
- rene-pancreas: 7
CURVA DI SOPRAVVIVENZA DEL
TRAPIANTO DI RENE (END-POINT: DIALISI)
Sopravvivenza del
graft (censurata per
la morte) %
100
50
37 %
UNOS registry
0
0
10
Anni
20
20
10
Sopravvivenza
dell’organo
trapiantato (%)
Sopravvivenza
dell’organo
trapiantato (%)
100
90
80
70
60
50
40
30
20
10 p=0.83
0
0
6
100
90
80
70
60
50
40
30
20
10 p=0.02
0
0
6
Trapianto singolo o doppio
Biopsia pre-trapianto: SI
Donatore > 60 anni
Trapianto singolo
Biopsia pre-trapianto: NO
Donatore < 60 anni
12
18
24
30
36
Trapianto singolo o doppio
Biopsia pre-trapianto: SI
Donatore > 60 anni
Trapianto singolo
Biopsia pre-trapianto: NO
Donatore > 60 anni
12
18
24
Mesi dal trapianto
30
36
Remuzzi et al., N Engl J Med, 2006
11