XV Corso di Aggiornamento in Nefrologia Medica
Milano 17 Novembre 2001
Il trapianto prima della dialisi
G.P. Segoloni
Cattedra di Nefrologia dell’Università di Torino
U.O.A.D.U. Nefrologia Dialisi e Trapianto (Dir. Prof G.Piccoli)
Azienda Ospedaliera S.Giovanni diTorino
Trapianto
renale
Emodialisi
In fase di uremia
terminale le scelte
possibili per garantire la
sopravvivenza del
paziente dovrebbero
essere 3
Dialisi
peritoneale
Trapianto renale preventivo
Autore
Tx
pre
referenza
D:Fryd 1968-84
1742
8%
Transplant Proc
XIX,1,1557-58; 1987
A.Foss 1984-96 Oslo (N)
141
39%
Transplantation ,6,64952 1998
Donnelly 1982-92 (CTS)
11.913
10%
Transpl Proc 28,6,356670 1996
A.Asderakis 1980- 95
Manchester (UK)
1463
11%
Nephrol Dial Transplant
13,1799-1803
Papalois VE 1984-98
Minnepolis (USA)
1849
21%
Transplantation (4),62531, 2000
R S
I I
D N
T
HDF
5%
CAPD
12%
APD
3%
IPD
1%
NI
0%
TX
1,1%
HF
1%
AHD
1%
First RRT modality in ESRD
incident patients - 1999
BHD
76%
Questa discordanza solleva 2 domande
fondamentali
• Quali sono le ragioni della trascurabile
percentuale di questa scelta nel nostro
Paese?
• Questo atteggiamento di rifiuto-diffidenza è
giustificato oggi ?
Il trapianto renale preventivo
fattori contrari all’utilizzazione del trapianto prima
della dialisi ( trapianto preventivo)
Risultati delle prime esperienze
Risultati attuali
Considerazioni finali
Andamento del trapianto da donatore vivente in
Italia nel periodo 1993-2000
140
120
132
119
118
119
107
100
80
79
82
88
Tx vivente
60
40
20
0
1993 1994 1995 1996 1997 1998 1999 2000
•Suppression of immunoresponsivness in uremia
Wilson
WEC, Kirkpatrick CH, Talmage DW Ann Intern Med 62,1-4, 1965
•Uremia as a state of immunodeficiency Birkelond SA Scand J
Immunol ;5;107-122: 1976
• Is uremia immunosuppressive in renal transplantation?
Hairy p, von Willebrand, Hochersted K et al tranaplantation ;34,268-72;
•Combined report on RDT in Europe 1981
Kramer P, Broyer M,
Brunner EP. Proc Eur Dial Tranplant Ass 1982, 19, 4,
……..indeed
several Authors have suggested
that chronic pretransplant dialysis may be
required to attain successful engraftment.
Il trapianto renale preventivo
fattori contrari all’utilizzazione del trapianto prima
della dialisi ( trapianto preventivo)
Risultati delle prime esperienze
Risultati attuali
Considerazioni finali
Can renal transplantation be done safely without
prior dialysis therapy ?
D Fryd , RJ Migliori Nl Ascher et al Transpl Proc vol
XIX,1, 1557-58,1987
Analizza 1742 trapianti consecutivi
eseguiti a Minneapolis nel periodo
1968 1884
Can renal transplantation be done safely without prior
dialysis therapy ?
D Fryd , RJ Migliori Nl Ascher et al Transpl Proc vol
XIX,1, 1557-58,1987
Survival (%)
Donor
All
Graft
dialysis
Yes (1404)
No (132)
CAD
Yes (624)
No (36)
CAD post Yes (236)
1979
No (22)
CAD Diab Yes (103)
No (19)
Recipient
1 year 3 years
1 year 3 years
76
80
71
66
77
77
84
76
89
88
80
83
86
86
87
95
67
64
58
37
67
46
63
53
78
70
71
42
84
58
75
67
Il trapianto renale preventivo
fattori contrari all’utilizzazione del trapianto prima
della dialisi ( trapianto preventivo)
Risultati delle prime esperienze
Risultati attuali
Considerazioni finali
Pre-emptive transplantation:- analysis of benefits and
hazards in 85 cases
S. Katz et al Transplantation 2, 52,351-55 1991
• 85 trapianti preventivi (1981-88)
paragonati con casi controllo “matched”
per demografica, clinica e terapia
• Analizzati per sopravvivenza paziente e
rene, incidenza del rigetto acuto, stato
nutrizionale e riabilitazione
Pre-emptive transplantation:- analysis of benefits and
hazards in 85 cases
S. Katz et al Transplantation 2, 52,351-55 1991
Pre.dialisi
postdialisi
Diabete
32/85
15/84
<0.01
LD/HLA id
15
7
ns
LD/aplo
32
32
ns
CAD/MM
4,2
4
ns
Trasfusi (%)
33
65
< 0.001
Pre-emptive transplantation:- analysis of benefits and
hazards in 85 cases
S. Katz et al Transplantation 2, 52,351-55 1991
Pre-dialisi
Sopravvivenza %
Post-dialisi
anno
1
3
3
4
5
Ricevente
83
81
76
73
73
90
81
80
77
76
77
77
75
71
67
92
82
82
82
79
Rene (CAD) 82
76
68
66
66
88
79
77
72
72
Rene (LD)
ns
ns
ns
Pre-emptive transplantation:- analysis of benefits and hazards
in 85 cases
S. Katz et al Transplantation 2, 52,351-55 1991
Pre –dialisi Post-dialisi
Hyperacute
0
0
NS
Accelerated
2
2
NS
Acute
28
26
NS
12 (43%)
7 (26%)
NS
Chronic
11
10
NS
NonCompliance
7
0
<0.001
irreversible
Pre-emptive transplantation:- analysis of benefits and
hazards in 85 cases
S. Katz et al Transplantation 2, 52,351-55 1991
• Incidenza di perdita rene per
noncompliance 9% ( 7/85)
3/3 (100%) perdita
ritrapianto per non
compliance
Pre-emptive transplantation:- analysis of benefits and
hazards in 85 cases
S. Katz et al Transplantation 2, 52,351-55 1991
Factors
Normal social act.
PRE
Full time vocational
Part-time vocational
Disabled
Normal social act.
Full time vocational
POST
Part-time vocational
Delayed rehabilit.
Disabled
Pre-emptive(69) Control (68)
49
36
15
9
44
38
6
1
10
38
22
13
21
42
20
9
7
18
p
ns
<0.05
ns
<0.05
ns
<0.01
ns
<0.05
<0.05
Thiel G. - LIVING KIDNEY DONOR TRANSPLANTATIONNEW DIMENSIONS-Transpl Int (1998) 11 (suppl 1): 50-56
…..and the job was lost in the
“dialysis trap”
Thiel G. - LIVING KIDNEY DONOR TRANSPLANTATION- NEW DIMENSIONSTranspl Int (1998) 11 (suppl 1): 50-56
Renal replacement therapy: the old way
loss of job (partial/ total)
invalidity pension (partial/total)
Thiel G. - LIVING KIDNEY DONOR TRANSPLANTATION- NEW DIMENSIONSTranspl Int (1998) 11 (suppl 1): 50-56
..no much longer than
a summer holiday time
Renal replacement
therapy: the new way of
pre-emp- tive
transplantation, planned
ahead for 2 years before
end- stage renal failure
maintained job / life quality
Pre-emptive transplantation for patients with renal
failure.
An argument against waiting until dialysis
V.E.Papalois et al Transplantation 70,625-631, 2000
1984-89
385 pre-empt.
1984 –98
1849 Tx
1990-98
9% CAD
27 % LD
9,3% CAD
30 % LD
1464 Non pre-empt.
Minneapolis
Pre-emptive transplantation for patients with renal failure An
argument against waiting until dialysis
V.E.Papalois et al Transplantation 70,625-631, 2000
Survival % 5 th year ND
D
p
CAD- recipient
LD- recipient
CAD graft
77
89,5
79
0.001
0.02
ns
RA 35
CR 19
39
22
ns
ns
92
85
0.006
RA 30
32
ns
CR 30
32
ns
93
93
83
LD graft
% noncompliance
0,97
2,1
Pre-emptive transplantation for patients with renal failure
An argument against waiting until dialysis
V.E.Papalois et al Transplantation 70,625-631, 2000
Cause of death ND(%) D(%)
Sepsis
0
Cardiac
0
5
p
0.05
8,3 0.03 …This finding can be
Pulmonary
Cerebrovasc.
0
1,4
2
2,7
ns
s
Malignancy
3
3,4
ns
Sudden death
4
4,6
ns
attributed partly to better
general health
pretransplantation, the
fact that the renal failure
was not advanced and
the beneficial effect of
pre-emptive transplant
Living donor kidney transplantation in predialysis
patients: experience of marginal donors in Europe and the
United States
P.Donnelly, P. Oman, R Henderson and G. Opelz
Transpl Proc vol 28,6,3566-3570, 1996
Analizza 11.913 trapianti da donatore vivente
1214 eseguiti in fase predialisi
9.275 trattati con emodialisi
1424 trattati con CAPD
Donnelly P et al Transplant proc 28,6;3566-70 1996
Pre-emptive
P< 0.01
Grat survival for off-spring donor
kidneys transplanted to parents with or
without prior dialysis
Donnelly P et al Transplant proc 28,6;3566-70 1996
Pre-emptive kidney transplantation: the attractive alternative
A Asderakis, and R Johnson
Renal Transplant Unit, - Manchester UK;
Materials and methods: 1463 consecutive first kidney
transplants performed in a single centre were analysed.
The 161 patients (11%) transplanted without prior dialysis
were compared with the 1302 patients who had been dialysed
prior to being transplanted. The pre-emptive group did not
differ from the dialysis group in respect of donor age, donor
and recipient gender, HLA mismatch, or cold ischaemic time,
although there were more live donor transplants within the preemptive group.
Nephrol Dial Transplant (1998) 13.1799-1803
Pre-emptive kidney transplantation: the attractive alternative
A Asderakis, and R Johnson
67% a 10 aa.
P = 0.05
56% a 10 aa.
Nephrol Dial Transplant (1998) 13.1799-1803
Pre-emptive kidney transplantation: the attractive alternative
A Asderakis, and R Johnson
Nephrol Dial Transplant (1998) 13.1799-1803
63%
54,5%
Pre-emptive kidney transplantation: the attractive alternative
A Asderakis, and R Johnson
Nephrol Dial Transplant (1998) 13.1799-1803
Pre-emptive kidney transplantation: the attractive alternative
A Asderakis, and R Johnson
Nephrol Dial Transplant (1998) 13.1799-1803
Rischio % assoluto di rigetto::
Effect of the use or non use of long term dialysis on the subsequent
survival of renal transplantas from living donor
Mange, Kevin C: Joffe, Marshall M.; Feldman, Harold I NEJM
344(10) 8 march 2001 726-731
• Sorgente: U.S renal data System  8481
trapianti da donatore vivente
• 6662 dopo inizio dialisi
• 1819 pre-emptive
• Analisi (unadjusted) ad 1 anno, da 1 a 2 anni, da 2
anni a fine dello studio
• Analisi multivariata ( adjusted) per i tre periodi
senza tener conto del rigetto acuto e per il
1°anno tenendo conto (adjusted) del rigetto acuto
Effect of the use or non use of long term dialysis on the subsequent
survival of renal transplants from living donor
Mange, Kevin C: Joffe, Marshall M.; Feldman, Harold I
NEJM 344(10) 8 march 2001 726-731
Reduction in the rate of allograft failure for pre-emptive
transplantation
1st year
2nd year
>3rd year
unadjusted
34% (0.01)
adjusted
52 % ( 0.002) 82% (0 .001) 86%( 0.001)
After adjustement for
1st AR in the 1st year
0.1
44% ( 0.07)
62 % (0.002)
Effect of the use or non use of long term dialysis on the subsequent
survival of renal transplants from living donor
Mange, Kevin C: Joffe, Marshall M.; Feldman, Harold I
NEJM 344(10) 8 march 2001 726-731
Results of logistic regression analysis of predictors of biopsy
confirmed acute rejection within six months after pre-emptive or
non pre-emptive transplantation
Duration of dialysis before Tx
vs pre-emptive transplantation
1st quartile ( 1-174 days)
Adjusted odd
ratio
1,6 (1,2 – 2.2)
2nd quartile (175-329 days)
2,3 ( 1,7- 3.0)
3rd quartile ( 330 – 623 days)
3.0 ( (2,3-3,9)
4th quartile (> 623 days)
4.2(3.3- 5.3
p
0.001
Considerazioni generali
Pre-emptive kidney transplantation
Vanrenterghem Y. & Verberckmoes R.
Nephrol Dial Transplant (1998) 13: 2466- 2468
….at present concerns about pre-emptive
transplantation are therefore much more
ethical than purely medical…..
1)At which point to
consider pre-emptive
transplantation?
Pre-emptive kidney transplantation Vanrenterghem Y. & Verberckmoes R.
Nephrol Dial Transplant (1998) 13: 2466- 2468
The unpredictability of the organ supply and the difficulty in
predicting for an individual patient the progress to renal
failure, may result in the transplantation of patients many
months before renal replacement therapy is indeed really
needed.
Too early transplantation will of course increase the overall costs
of renal replacement therapy as the same organ could be used in
the meantime to transplant a patient who is already on an
expensive form of renal replacement therapy.
Pre-emptive kidney transplantation Vanrenterghem Y. & Verberckmoes R.
Nephrol Dial Transplant (1998) 13: 2466- 2468
Considering pre-emptive transplantation is therefore
only acceptable if the evolution of the underlying
renal disease is well documented and a prognosis of
the progression of the renal disease can be made
with a high degree of accuracy…..
….As most of the patients with a creatinine
clearance << 15 ml/min will become dialysis
dependent within 1 year, it seems reasonable to put
patients on the waiting list only when creatinine
clearance has reached < 15 ml/min. This policy
however is also only possible if the overall mean
waiting time for finding a suitable kidney is no
longer than 1 year. ..
Pre-emptive kidney transplantation
Vanrenterghem Y. & Verberckmoes R.
Nephrol Dial Transplant (1998) 13: 2466- 2468
Conclusions
• In conclusion, pre-emptive transplantation is for medical as well as
for socio-economical reasons the preferred mode of renal
replacement therapy.
•In the context of the present organ shortage and the long waiting
time for those patients already on dialysis, pre- emptive
transplantation from CAD cannot be realised.
•However in countries with a high donation rate, where the number
of available cadaveric donor kidneys equals the yearly demand, preemptive transplantation is justifiable when either medical or
socioeconomical compelling reasons are present.
Pre-emptive kidney transplantation
Vanrenterghem Y. & Verberckmoes R.
Nephrol Dial Transplant (1998) 13: 2466- 2468
Conclusions
In case of living donor , preemptive transplantation may be
the treatment of choice
Per quanto riguarda la nostra
realtà…..
Il trapianto renale da cadavere prima dell’inizio
del trattamento dialitico rappresenta una
soluzione limitata a candidati con situazioni
cliniche particolari
• diabetici uremici di tipo I nel programma
combinato di pancreas e rene
• pazienti con ossaluria primitiva in
programma per trapianto combinato di
fegato-rene
A.Humar et al Annals of Surgery vol 231,n°2, 269-275 , 2000
Fattori di rischio per trombosi e infezioni
Trombosi:Fattori di rischio
Età don ( aa)
< 20 1,8%
20/40 3,7%
Anticoag. Si/No.
Dialisi No/Si
4%
11,4%
11 %
3%
> 40 16 %
.06
0.1
Nel caso si programmi un
trapianto renale da donatore
vivente
• Non esistono limitazioni di nessun tipo al trapianto
“preventivo”
• Nelle Linee Guida per il trapianto da donatore
vivente (Centro Nazionale Trapianti 10 gennaio 2001) è stato
rimossa (per intervento del nefrologo) la primitiva
indicazione di condizionare il trapianto da vivente
ad una precedente iscrizione in lista di attesa da
cadavere, proprio per permettere questo tipo di
soluzione
Anno Accademico 2000-2001
XXVI corso di Aggiornamento in Nefrologia Dialisi e
Trapianto – riunione del 01
• Su 22 nefrologi in rappresentanza dei 22
centri piemontesi
– 19 erano perplessi-contrari al trapianto renale
preventivo
– 3 favorevoli
• Centro Pediatrico
• Centro proponente
• Centro dialisi adulti
Attività di trapianto preventivo in
centri con diversa esperienza nel
trapianto da donatore vivente
periodo
N° Tx
Funzionanti
Policlinico –
Croff ( Prof
Ponticelli)
09/08/198709/10/01
17
15
Torino- Centro
A.Vercellone
24/07/00 04/03/01
4
4
Centro Trapianti Renali “A.Vercellone”
U.O.A.D.U. Nefrologia Dialisi Trapianto
Az. Osped S. Giovanni di Torino
Tipologia
Numero
%
Trapianti renali
1386
Da cadavere
1357
98 %
Da vivente
31
2
Da vivente (1999)
15
48 %
Sviluppo del programma trapianto da donatore
vivente presso il Centro “A. Vercellone”di Torino
25
20
Tx-LD
in attesa
15
10
5
0
1981-90
91-98
99-00
2001
Dalla discussione del
XXIV Simposio Nefrologico Veneziano
22 marzo 1997
Trapianto di rene da donatore vivente: stato dell’arte e
degli aspetti etici della donazione
• (Ponticelli) :…visto che ho la parola , ma solo per
30 secondi …. io credo che noi nefrologi siamo i
maggiori responsabili dell’assoluta mancanza di
sviluppo del trapianto da vivente in Italia . La
grande maggioranza dei nostri pazienti o non
viene informata o viene scoraggiata fin dall’inizio
per avere un trapianto da vivente ……
In conclusione
• Il trapianto renale preventivo merita oggi una
riconsiderazione da parte di tutti i nefrologi in
quando i dati disponibili ne documentano
esaurientemente la superiorità in termini di
sopravvivenza ( paziente e rene) riabilitazione
migliore.
• Ogni paziente orientato verso il trapianto da
vivente deve essere messo al corrente della
possibilità di essere trapiantato
preventivamente