10 jahre aboi-ld-ntx in deutschland · 10 jahre aboi-ld-ntx in deutschland ergebnisse und...
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10 Jahre ABOi-LD-NTX in Deutschland Ergebnisse und Erfahrungen in Freiburg
A. Kramer-Zucker und S. Zschiedrich Hinterzarten, 29. November 2014
2
Quelle: "TK Aktuell" Ausgabe 3/2004
A1 O
m, 61 Jahre
ADPKD
85 kg
w, 63 Jahre
gesund
60 kg
10 Jahre Follow up:
S-Kreatinin: 2004 1.7 mg/dl
2014 2.2 mg/dl
EW/Krea: 2014 0.17 g/g
anti-A 1:256
1. Freiburger ABO-inkompatible Nierentransplantation
1. April 2004
3
Transplantationszentrum Freiburg
Nierentransplantationen 3464 (seit 1968)
Nierenlebendspende-Transplantationen 626 (seit 1982)
ABO-inkompatible LD-NTx 100 (seit 2004) Stand 28.11.2014
4
Prednisone 30 mg/d
Tacrolimus 12-15 ng/ml 6-12 ng/ml 4-8 ng/ml
Mycophenolate 2 x 1 g/d 2 x 1 g/d
50
0
25
0
10
0
5 mg
Erhaltungs-Th.
-30 -7 -5 0 4 14 90
Rit
uxi
mab
IA IA
Bas
ilixi
mab
variable
IA B
asili
xim
ab
≤1:4 ≤ 1:8 ≤ 1:16
IA PE
20 mg 25
0
Protokoll ABO inkompatible Nierentransplantation
5
Protokoll ABO kompatible Nierentransplantation
Prednisone
Tacrolimus 8-12 ng/ml 6-12 ng/ml 4-8 ng/ml
Mycophenolate 2 x 1 g/d 2 x 1 g/d
25
0
12
5
50 mg 5 mg 20 mg 15 mg
Erhaltungs-Th.
0 4 14 90 B
asili
xim
ab
Bas
ilixi
mab
6
ABOi KTx
(n=100)
ABOc KTx
(n=248)
Flowchart Auswertung LD-NTX 2004-2014
ABOi KTx
(n=97)
ABOc KTx
(n=106)
CSA-
based IS
(n=3)
CSA-
based IS
(n=141)
Lost to
follow up
(n=1)
7
Charakteristika ABOi- vs. ABOc-Kohorte
Patient and donor characteristics ABOi KTx (n=97) ABOc KTx (n=106) p-Value
Recipient age at Tx (years) 47 ± 11 [18-67] 49 ± 12 [18-73] 0.15
Donor age at Tx (years) 51 ± 9 [27-75] 52 ± 9 [29-73] 0.51
Recipient gender female/male (%) 37/60 (38/62) 40/66 (38/62) 1.0
Donor gender female/male (%) 62/35 (64/36) 62/44 (58/42) 0.47
Related donors (%) 31 (32) 30 (28) 0.65
Unrelated donors (%) 66 (68) 76 (72) 0.65
Pre-emptive Tx (%) 21 (22) 27 (27) 0.62
Time on dialysis before Tx (months) 24 ± 29 [0-139] 21 ± 31 [0-145] 0.38
Hypertension at Tx (%) 88 (91) 97 (92) 1.00
Diabetes mellitus at Tx (%) 4 (4) 11 (10) 0.11
Coronary heart disease at Tx (%) 8 (8) 20 (19) 0.04*
Prior malignancy (%) 7 (7) 11 (10) 0.47
8
Patientenüberleben ABOi vs. ABOc
99%
80%
0 1 2 2 4 3 6 4 8 6 0 7 2 8 4 9 6 1 0 8 1 2 0
0
5 0
1 0 0
T im e [m o n th s ]
Pe
rce
nt
su
rviv
al
A B O in c o m p a tib le
A B O c o m p a tib le
p = 0 .0 0 7 1 ( lo g -ra n k te s t)?
9
Patientenüberleben ABOi vs. ABOc
Death cause
ABOi KTx (n=1)
Patient # 6
clostridium difficile sepsis (d 115)
ABOc KTx (n=9)
Patient # 16
Patient # 18
Patient # 20
Patient # 27
Patient # 50
Patient # 62
Patient # 86
Patient # 87
Patient # 97
progressive B-cell lymphoma, leucencephalopathy (d 896)
cardiovascular event suspected (d 1581)
metastasizing oesophageal cancer (d 276)
candida sepsis (d 2001)
aspergillus sepsis (d191)
liver failure in ADPKD/PLD (d1054)
severe pneumocystis jiroveci pneumonia (d 383)
urothelium carcinoma (d 195)
cava thrombosis, right ventricular failure (d 47)
10
Patientenüberleben ABOi vs. ABOc
99%
80%
89%
0 1 2 2 4 3 6 4 8 6 0 7 2 8 4 9 6 1 0 8 1 2 0
0
5 0
1 0 0
m o n th s
Pe
rce
nt
su
rviv
al
A B O in c o m p a tib le
A B O c o m p a tib le
A B O c o m p a tib le (a ll)
p = 0 .0 5 6 5 ( lo g -ra n k te s t)
11
Immunologischer Charakteristika ABOi vs. ABOc
Immunological risk factors and comorbidity ABOi KTx (n=97) ABOc KTx (n=106) p-Value
HLA mismatches (A/B/DR)
3.80 ± 1.37
3.57 ± 1.54
0.25
1st Tx (%)
83 (86)
88 (83)
0.70
2nd or 3rd Tx (%)
14 (14)
18 (17)
0.70
HLA-indentical sibling as donor (%)
1 (1)
3 (3)
0.62
Panel reactive antibodies 0-19 % (%)
20-79 % (%)
> 80 % (%)
94 (97)
2 (2)
1 (1)
99 (93)
6 (6)
1 (1)
0.34
0.28
1.00
12
97 Patienten
A1 O
A2 O
AB O
B O
A1 B
A2 B
AB B
B A
AB A
39
13 13
1
9
4
4
8 6
ABOi-Kohorte
Blutgruppen-Konstellationen
13
Transplantatüberleben ABOi vs. ABOc
94%
88%
death censored
0 1 2 2 4 3 6 4 8 6 0 7 2 8 4 9 6 1 0 8 1 2 0
0
5 0
1 0 0
T im e [m o n th s ]
Pe
rce
nt
su
rviv
al
A B O -in c o m p a tib le
A B O -c o m p a tib le
p = 0 .2 5 ( lo g -ra n k te s t)
14
Transplantatüberleben ABOi vs. ABOc
Graft loss cause
ABOi KTx (n=4)
Patient # 10
Patient # 45
Patient # 49
Patient # 61
chronic antibody-mediated rejection (d 2266)
arterial graft thrombosis (d 4)
recurrent FSGS (d 579)
chronic antibody mediated rejection (d 110)
ABOc KTx (n=7)
Patient # 2
Patient # 3
Patient # 5
Patient # 38
Patient # 40
Patient # 42
Patient # 62
Patient # 81
bleeding (d 1)
hyperacute rejection (d 0)
chronic antibody mediated rejection (d 2325)
acute rejection (external data) (d 870)
arterial graft thrombosis (d 0)
chronic antibody mediated rejection (d 1916)
chronic antibody mediated rejection (d 875)
haemorrhagic shock/retroperitoneal haematoma (d 66)
15
Transplantatüberleben ABOi vs. ABOc
death censored
94%
88% 89.7%
0 1 2 2 4 3 6 4 8 6 0 7 2 8 4 9 6 1 0 8 1 2 0
0
5 0
1 0 0
m o n th s
Pe
rce
nt
su
rviv
al
A B O -in c o m p a tib le
A B O -c o m p a tib le
A B O c o m p a tib le (a ll)
p = 0 .4 9 ( lo g -ra n k te s t)
17
Weitere Ergebnisse ABOi vs. ABOc
ABOi
(n = 97)
ABOc
(n = 106) p
Bei Entlassung
S-Kreatinin
(mg/dl)
1.52 ± 0.47
[0.7 – 3.7]
1.50 ± 0.4
[0.7 – 2.8] 0.75
Last follow-up
Nachbeobachtung
(Median)
58 ± 36
[3-128]
48 ± 29
[2-122] 0.03*
S-Kreatinin
(mg/dl)
1.48 ± 0.50
[0.7 – 3.86]
1.48 ± 0.42
[0.6 – 2.6] 0.9
eGFR (MDRD)
(ml/min/1,73m2)
53 ± 15
[18 - 92]
52 ± 15
[23 - 115] 0.74
Eiweiß/Kreatinin i.U.
(g/g)
0.22 ± 0.52
[0.03-3.87]
0.15 ± 0.13
[0.02-0.88] 0.22
18
Weitere Ergebnisse ABOi vs. ABOc
0 1 2 3 4 5 6 7 8 9 1 0
0
2 0
4 0
6 0
8 0
F o llo w -u p [y e a rs ]
eG
FR
[m
l/m
in/1
.73
m²] A B O i K T x
A B O c K T x
A t r is k :
8 3 7 4 6 6 5 4 4 5 3 7 2 6 2 0 8 2
8 8 7 8 6 2 4 9 3 9 3 0 9 2 1 1
ABOi
ABOc
19
ABOi
(n = 97)
ABOc
(n = 106) p
Nierenbiopsien
(Protokoll+Indikation) 74 (76%) 79 (74%) 0.62
Histologie
humorale Rej.
zelluläre Rej.
CNI-Tox.
PVAN
9 (9%)
13 (14%)
24 (25%)
4 (4%)
11 (10%)
12 (12%)
19 (18%)
4 (4%)
1.00
0.67
0.23
1.00
Infektionen
Hospitalisierung
Sepsis
CMV
PjP
37 (38%)
8 (8%)
5 (5%)
1 (1%)
37 (35%)
8 (8%)
11 (10%)
2 (2%)
0.56
1.00
0.20
1.00
Malignome
Haut
andere
PTLD
6 (6%)
5 (5%)
1 (1%)
0 (0)
5 (5%)
2 (2%)
3 (3%)
1 (1%)
0.76
0.26
0.62
1.00
Komplikationen ABOi vs. ABOc
20
Chirurgische Eingriffe/Komplikationen ABOi vs. ABOc
Simultaneous operative procedures ABOi KTx (n=97) ABOc KTx (n=106)
Total (%) 33 (34.0) 33 (31.1)
Simultaneous nephrectomy (%)
Graft kidney nephrectomy (%)
Polycystic kidney nephrectomy (%)
Native kidney nephrectomy (%)
Appendectomy
30 (31.0)
6 (6.2)
23 (23.7)
1 (1.0)
5 (5.2)
29 (27.4)
4 (3.8)
24 (22.6)
1 (0.9)
4 (3.8)
Surgical complications ABOi KTx (n=97) ABOc KTx (n=106) p-Value
Operative revisions yes/no (%) 37 (38.1) 25 (23.6) 0.032*
Bleeding/Hematoma with required surgery (%)
Lymphocele total (%)
Lymphocele with required surgery (%)
Ureteral complications
20 (20.6)
32 (33.0)
19 (19.6)
11 (11.3)
14 (13.2)
16 (15.1)
8 (7.5)
9 (8.5)
0.19
0.003**
0.013*
0.64
21
Zusammenfassung Teil 1:
10 Jahre ABOi-LD-NTX in Deutschland
= 100 ABOi-LD-NTX in Freiburg
Sehr gute Ergebnisse Patienten- und Transplantatüberleben
Rejektions-, Infektions- und Malignomskomplikationen vergleichbar mit ABOk-LD-NTX-Kohorte im gleichen Zeitraum
Gute Ergebnisse in der Langzeitfunktion vergleichbar mit ABOk-LD-NTX-Kohorte im gleichen Zeitraum
Erhöhte Inzidenz von operativen Lymphozelen-Revisionen
23
Prednison 30mg/d Tacrolimus 12-15ng/ml 6-12ng/ml 4-8ng/ml Mycophenolat 2 x 1g/d 2 x 1g/d
50
0
25
0
10
0
25 5mg
Erhaltung
Rit
uxi
mab
-30 -7 -5 0 4 14
≤1:4
IA IA IA IA
Bas
ilixi
mab
≤1:8 ≤1:16
IA
Bas
ilixi
mab
TMP/SMX 6 Mon., Valganciclovir 3 Mon., Fluconazol 3 Wo.
7
IVIG
Freiburger ABOi-Protokoll
25
0
2 2
6
4 5
9 8
15
19
11
9
5
2
24
Hohe Isohämagglutinin-Titer
97 Patienten
IgG 0 1 2 4 8 16 32 64 128 256 512 1024 2048
27 Patienten
16 Patienten
≥ 1:256 Wilpert J, Geyer M, Teschner S, Schaefer T, Pisarski P, Schulz-Huotari C, Gropp A, Wisniewski U, Goebel H, Gerke P, Walz G, Donauer J. ABO-incompatible kidney transplantation-proposal of an intensified apheresis strategy for patients with high initial isoagglutinine titers. J Clin Apher. 2007;22(6):314-22.
≥ 1:512 Uchida J, Iwai T, Kato M, Machida Y, Naganuma T, Kumada N, Yoshimura R, Kawashima H, Kim T, Nakatani T. A novel approach to successful ABO-incompatible high-titer renal transplantation. Transplant Proc. 2008 Sep;40(7):2285-8.
Chung BH, Lim JU, Kim Y, Kim JI, Moon IS, Choi BS, Park CW, Kim YS, Yang CW. Impact of the baseline anti-A/B antibody titer on the clinical outcome in ABO-incompatible kidney transplantation. Nephron Clin Pract. 2013;124(1-2):79-88.
25
0
5
10
15
20
25
0 2 4 6 8 10 12 14
Anzahl der
Verfahren
IA/PP
IgG-Titer 0 1 2 4 8 16 32 64 128 256 512 1024 2048
Hohe Isohämagglutinin-Titer
29
ABOi
≤ 1:128
(n = 70)
ABOi
≥ 1:256
(n = 27)
p
Empfänger
Alter bei Tx 46 ± 11 [20-67] 47 ± 10 [18-64] 0.81
Empfänger
Geschlecht w/m
28/42
(40/60%)
9/18
(32/68%) 0.63
Spender
Alter bei Tx 53 ± 9 [27-75] 47 ± 8 [29-73] 0.02
Spender
Geschlecht w/m
44/26
(63/37%)
18/9
(68/32%) 0.81
Lebendspende
familiär 23 (33%) 8 (30%) 0.83
HLA mismatches
(A/B/DR) 3.81 ± 1.26 3.84 ± 1.67 0.94
Baseline Charakteristika
Hohe Isohämagglutinin-Titer
30
Hohe Isohämagglutinin-Titer
ABOi
≤ 1:128
(n = 70)
ABOi
≥ 1:256
(n = 27)
0
5
10
15
20
25
1 2 3 4 5
4.8 10.2 13.1 8.3
Vorbereitung
Verfahren prä-OP
(Anzahl IA / PP) Stationäre
Vorbereitungszeit
(Tage)
(p 5.0 E-11)
(p 3.0 E-5)
* *
31
Hohe Isohämagglutinin-Titer
ABOi
≤ 1:128
(n = 70)
ABOi
≥ 1:256
(n = 27)
p
bei Entlassung:
S-Kreatinin
(mg/dl) 1.52 1.51 0.92
eGFR (MDRD)
(ml/min/1,73m2) 50 [23-100] 52 [27-78] 0.57
aktuell (Nachbeobachtungszeit 3-120 Monate):
Transplantatüberleben 94% 100% 0.57
S-Kreatinin
(mg/dl) 1.51 1.41 0.45
eGFR (MDRD)
(ml/min/1,73m2) 52 [11-92] 54 [31-82] 0.50
Eiweiß/Kreatinin i.U.
(g/g) 0.19 0.30 0.77
Tx-Nierenfunktion
32
ABOi
≤ 1:128
(n = 70)
ABOi
≥ 1:256
(n = 27)
p
1. NTx 59 (84%) 24 (89%) 0.87
2. NTx 10 (14%) 3 (11%) 0.71
HLA mismatches
(A/B/DR) 3.81 ± 1.26 3.84 ± 1.67 0.94
präemptive Tx 11 (16%) 9 (33%) 0.13
Dialysezeit
(Monate) 28 ± 30 17 ± 21 0.13
Blutgruppe
A1/0
A2/0
andere
21
8
41
18
5
4
3.0 E-4 (41%)
(59%)
(85%)
(15%)
Unterschiede Baseline Charakteristika
Hohe Isohämagglutinin-Titer
33
ABOi
≤ 1:128
(n = 70)
ABOi
≥ 1:256
(n = 27)
p
1. NTx 59 (84%) 24 (89%) 1.00
2. NTx 10 (14%) 3 (11%) 1.00
HLA mismatches
(A/B/DR) 3.81 ± 1.26 3.84 ± 1.67 0.94
präemptive Tx 11 (16%) 8 (32%) 0.09
Dialysezeit
(Monate) 28 ± 30 17 ± 21 0.13
Blutgruppe
A1/0
A2/0
andere
21
8
41
16
5
4
3.0 E-4 (41%)
(59%)
(84%)
(16%)
ABOi
≥ 1:512
(n = 16)
p
11 ± 13 0.04
12
3
1 (B/0)
3.0 E-4 (94%)
(6%)
Unterschiede Baseline Charakteristika
Isotiter 1/Dialysezeit
Derzeitiges Protokoll:
akzeptable Titerhöhe ≤ 1:1024
keine Drop-outs wegen Titer
Hohe Isohämagglutinin-Titer
Freiburger ABOi-Protokoll
Prednison 30mg/d Tacrolimus 12-15ng/ml 6-12ng/ml 4-8ng/ml Mycophenolat 2 x 1g/d 2 x 1g/d
50
0
25
0
10
0
25 5mg
Erhaltung
TMP/SMX 6 Mon., Valganciclovir 3 Mon., Fluconazol 3 Wo.
25
0
34
Rit
uxi
mab
-30 -7 -5 0 4 14
≤1:4
IA IA IA IA
Bas
ilixi
mab
≤1:8 ≤1:16
IA
Bas
ilixi
mab
7
IVIG
Antigen-spezifisch
nicht-regenerierbar
nicht-Antigen-spezifisch
Protein A
regenerierbar
35
Besonderheiten in der Vorbereitung
Antigen-spezifisch vs. semi-selektiv (nicht Ag-spezif.)
Immunadsorptionsäulen
Wahrmann M, Schiemann M, Marinova L, Körmöczi GF, Derfler K, Fehr T, Stussi G, Böhmig GA. Anti-A/B antibody depletion by semiselective versus ABO blood group-specific immunoadsorption. Nephrol Dial Transplant. 2012 May;27(5):2122-9.
1 1
2 1
1
3 4
1
3
1
2
2
1
1
2
1
1 2 3 4
36
Isohämagglutinin-Titer
27. Patienten
256 512 1024 2048 IgG
IgM
256
128
64
32
16
8
Besonderheiten in der Vorbereitung
37
Vorbereitung R
itu
xim
ab
-30 -7 -5 0 4 14
≤1:4
IA IA PP IA
Bas
ilixi
mab
≤1:8 ≤1:16
IA
Bas
ilixi
mab
7
Antigen-spezifisch
nicht-regenerierbar
nicht-Antigen-spezifisch
regenerierbar
+
Plasmapherese
1.5-2x PV
2.5-3x PV
38
0
1
2
3
4
5
6
7
8
9
10
11
12
13
4.1
.13
4.2
.13
4.3
.13
4.4
.13
4.5
.13
4.6
.13
4.7
.13
4.8
.13
4.9
.13
4.1
0.1
3
4.1
1.1
3
4.1
2.1
3
4.1
3.1
3
4.1
4.1
3
4.1
5.1
3
4.1
6.1
3
4.1
7.1
3
4.1
8.1
3
4.1
9.1
3
4.2
0.1
3
4.2
1.1
3
4.2
2.1
3
4.2
3.1
3
4.2
4.1
3
4.2
5.1
3
4.2
6.1
3
4.2
7.1
3
4.2
8.1
3
4.2
9.1
3
IgG
IgM
0
1:1
1:2
1:4
1:8
1:16
1:32
1:64
1:128
1:256
1:512
1:1024
1:2048
OP -2 -4 -6 -8 -10 -12 -14 2 4 6 8 10 12 Tage
Titer
Pat (#85) w, 44j Donor: Schwester
A1/O ADPKD
präemptiv
E-Krea
0.84
8 Wo:
borderline
Rejektion
18 Mo:
Krea
1.00
Besonderheiten in der Vorbereitung
0
1
2
3
4
5
6
7
8
9
10
11
12
13
24
.01
.201
2
25
.01
.201
2
26
.01
.201
2
27
.01
.201
2
28
.01
.201
2
29
.01
.201
2
30
.01
.201
2
31
.01
.201
2
01
.02
.201
2
02
.02
.201
2
03
.02
.201
2
04
.02
.201
2
05
.02
.201
2
06
.02
.201
2
07
.02
.201
2
08
.02
.201
2
09
.02
.201
2
10
.02
.201
2
11
.02
.201
2
12
.02
.201
2
13
.02
.201
2
14
.02
.201
2
15
.02
.201
2
16
.02
.201
2
17
.02
.201
2
18
.02
.201
2
19
.02
.201
2
20
.02
.201
2
21
.02
.201
2
22
.02
.201
2
23
.02
.201
2
24
.02
.201
2
25
.02
.201
2
26
.02
.201
2
27
.02
.201
2
28
.02
.201
2
29
.02
.201
2
01
.03
.201
2
02
.03
.201
2
39
IgG
IgM
0
1:1
1:2
1:4
1:8
1:16
1:32
1:64
1:128
1:256
1:512
1:1024
1:2048
OP -2 -4 -6 -8 -10 -12 -14 2 4 6 8 10 12 Tage
Titer
Pat (#75) w, 49j Donor: Ehemann
A2/O IgAN
HD 26 Mo
14
IA: Ag-spezif.
-16 -18 -20
18 IA 2PP 8 IA
E-Krea
1.10
30 Mo:
Krea
1.26
Besonderheiten in der Vorbereitung
40
Besonderheiten in der Vorbereitung
ABO – Antigendichten/Häufigkeiten
Quelle: Körmöczi „ABO-inkompatible Nierentransplantation“
41
Besonderheiten in der Vorbereitung
A2 Donor-Organe
Rydberg L. ABO-incompatibility in solid organ transplantation. Transfus Med. 2001 Aug;11(4):325-42.
Rydberg L, Breimer ME, Samuelsson BE, Brynger H. Blood group ABO-incompatible (A2 to O) kidney transplantation in human subjects: a clinical, serologic, and biochemical approach. Transplant Proc. 1987 Dec;19(6):4528-37.
Göteborg 1974 – 1988
- 21 postmortale NTx
- A2 O
- keine Isotiter-Reduktion
Transplantatüberleben
- 9 Transplantate: < 1Monat
- 12 Transplantate: Monate - Jahre
0
1
2
3
4
5
6
7
8
9
10
11
12
13
24
.01
.201
2
25
.01
.201
2
26
.01
.201
2
27
.01
.201
2
28
.01
.201
2
29
.01
.201
2
30
.01
.201
2
31
.01
.201
2
01
.02
.201
2
02
.02
.201
2
03
.02
.201
2
04
.02
.201
2
05
.02
.201
2
06
.02
.201
2
07
.02
.201
2
08
.02
.201
2
09
.02
.201
2
10
.02
.201
2
11
.02
.201
2
12
.02
.201
2
13
.02
.201
2
14
.02
.201
2
15
.02
.201
2
16
.02
.201
2
17
.02
.201
2
18
.02
.201
2
19
.02
.201
2
20
.02
.201
2
21
.02
.201
2
22
.02
.201
2
23
.02
.201
2
24
.02
.201
2
25
.02
.201
2
26
.02
.201
2
27
.02
.201
2
28
.02
.201
2
29
.02
.201
2
01
.03
.201
2
02
.03
.201
2
42
IgG
IgM
0
1:1
1:2
1:4
1:8
1:16
1:32
1:64
1:128
1:256
1:512
1:1024
1:2048
OP -2 -4 -6 -8 -10 -12 -14 2 4 6 8 10 12 Tage
Titer
Pat (#75) w, 49j Donor: Ehemann
A2/O IgAN
HD 26 Mo
14
IA: Ag-spezif.
-16 -18 -20
18 IA 2PP 8 IA
E-Krea
1.10
30 Mo:
Krea
1.26
Besonderheiten in der Vorbereitung
43
Zieltiter
Transplantationszentrum: zentrumseigener Zielbereich
≤ 1:8 Genberg H, Kumlien G, Wennberg L, Tyden G. The efficacy of antigen-specific immunoadsorption and rebound of anti-A/B antibodies in ABO-incompatible kidney transplantation. Nephrol Dial Transplant. 2011 Jul;26(7):2394-400.
Zieltiter-Bereiche anderer Zentren
≤ 1:4 Tydén G, Donauer J, Wadström J, Kumlien G, Wilpert J, Nilsson T, Genberg H, Pisarski P, Tufveson G. Implementation of a Protocol for ABO-incompatible kidney transplantation--a three-center experience with 60 consecutive transplantations. Transplantation. 2007 May 15;83(9):1153-5.
≤ 1:8 Chung BH, Lim JU, Kim Y, Kim JI, Moon IS, Choi BS, Park CW, Kim YS, Yang CW. Impact of the baseline anti-A/B antibody titer on the clinical outcome in ABO-incompatible kidney transplantation. Nephron Clin Pract. 2013;124(1-2):79-88.
≤ 1:16 Montgomery RA, Locke JE, King KE, Segev DL, Warren DS, Kraus ES, Cooper
M, Simpkins CE, Singer AL, Stewart ZA, Melancon JK, Ratner L, Zachary AA,
Haas M. ABO incompatible renal transplantation: a paradigm ready for broad
implementation. Transplantation. 2009 Apr 27;87(8):1246-55.
≤ 1:32 Tanabe K, Ishida H, Shimizu T, Omoto K, Shirakawa H, Tokumoto T. Evaluation of two different preconditioning regimens for ABO-incompatible living kidney donor transplantation. A comparison of splenectomy vs. rituximab-treated non-splenectomy preconditioning regimens. Contrib Nephrol. 2009;162:61-74.
44
Chung BH, Lim JU, Kim Y, Kim JI, Moon IS, Choi BS, Park CW, Kim YS, Yang CW. Impact of the baseline anti-A/B antibody titer on the clinical outcome in ABO-incompatible kidney transplantation. Nephron Clin Pract. 2013;124(1-2):79-88.
Nu
mb
er
of p
atie
nts
with
re
sp
ective
≤ 1:8 n=32 n=8
Zieltiter-Bereiche anderer Zentren
45
Chung BH, Lim JU, Kim Y, Kim JI, Moon IS, Choi BS, Park CW, Kim YS, Yang CW. Impact of the baseline anti-A/B antibody titer on the clinical outcome in ABO-incompatible kidney transplantation. Nephron Clin Pract. 2013;124(1-2):79-88.
Chung BH, Lee JY, Kang SH, Sun IO, Choi SR, Park HS, Kim JI, Moon IS, Choi BS, Park CW, Kim YS, Yang CW. Comparison of clinical outcome between high and low baseline anti-ABO antibody titers in ABO-incompatible kidney transplantation. Ren Fail. 2011;33(2):150-8.
Protokolle anderer Zentren
≤ 1:8
0
1
2
3
4
5
6
7
8
9
10
11
12
13
46
IgG
IgM
0
1:1
1:2
1:4
1:8
1:16
1:32
1:64
1:128
1:256
1:512
1:1024
1:2048
OP
geplant
-2 -4 -6 -8 -10 -12 -6 Mo Tage
Titer
Pat (#94) w, 50j Donor: Lebenspartner
A1/O chron. GN
HD 16 Mo
Abbruch bei
pulmonalem Infekt
RTX (375 mg/m2)
-4 Wo
Besonderheiten in der Vorbereitung
0
1
2
3
4
5
6
7
8
9
10
11
12
13
47
IgG
0
1:1
1:2
1:4
1:8
1:16
1:32
1:64
1:128
1:256
1:512
1:1024
1:2048
OP -2 -4 -6 -8 2 4 6 8 10 12 Tage
Titer
Pat (#94) w, 50j Donor: Lebenspartner
A1/O chron. GN
HD 16 Mo
IgM
6 Wo
Pause
14
E-Krea
1.00
5 Mo:
Krea
1.00
Besonderheiten in der Vorbereitung
48
Prednison 30mg/d Tacrolimus 12-15ng/ml 6-12ng/ml Mycophenolat 2 x 1g
50
0
25
0
10
0
25
Rit
uxi
mab
-30
≤1:8
IA IA IA
Bas
ilixi
mab
Bas
ilixi
mab
-7 -5 0 4 14 7
ABOi-Protokoll
25
0
Habicht A, Bröker V, Blume C, Lorenzen J, Schiffer M, Richter N, Klempnauer J, Haller H, Lehner F, Schwarz A. Increase of infectious complications in ABO-incompatible kidney transplant recipients--a single centre experience. Nephrol Dial Transplant. 2011 Dec;26(12):4124-31.
Prednison 20mg/d Tacrolimus 5-8ng/ml Mycophenolat 2x 0.5g
0
1
2
3
4
5
6
7
8
9
10
11
12
13
24
.01
.201
2
25
.01
.201
2
26
.01
.201
2
27
.01
.201
2
28
.01
.201
2
29
.01
.201
2
30
.01
.201
2
31
.01
.201
2
01
.02
.201
2
02
.02
.201
2
03
.02
.201
2
04
.02
.201
2
05
.02
.201
2
06
.02
.201
2
07
.02
.201
2
08
.02
.201
2
09
.02
.201
2
10
.02
.201
2
11
.02
.201
2
12
.02
.201
2
13
.02
.201
2
14
.02
.201
2
15
.02
.201
2
16
.02
.201
2
17
.02
.201
2
18
.02
.201
2
19
.02
.201
2
20
.02
.201
2
21
.02
.201
2
22
.02
.201
2
23
.02
.201
2
24
.02
.201
2
25
.02
.201
2
26
.02
.201
2
27
.02
.201
2
28
.02
.201
2
29
.02
.201
2
01
.03
.201
2
02
.03
.201
2
49
IgG
IgM
0
1:1
1:2
1:4
1:8
1:16
1:32
1:64
1:128
1:256
1:512
1:1024
1:2048
OP -2 -4 -6 -8 -10 -12 -14 2 4 6 8 10 12 Tage
Titer
Pat (#75) w, 49j Donor: Ehemann
A2/O IgAN
HD 26 Mo
14
IA: Ag-spezif.
-16 -18 -20
18 IA 2PP 8 IA
E-Krea
1.10
Outcome – Freiburger Daten
50
Outcome – Freiburger Daten
ABOi
≤ 1:128
(n = 70)
ABOi
≥ 1:256
(n = 27)
p
Nach Transplantation:
IA / PP post-OP
(Anzahl Patienten) 13 (19%) 14 (52%) 7.0 E-4
IA / PP post-OP
(Anzahl Verfahren)
0.2 ± 0.8
[0-5]
1.6 ± 2.2
[0-8] 6.0 E-5
Stat. Aufenthalt
(Tage) 20.2 ± 9.1 18.8 ± 4.1 0.46
Chir. Revisionen
Blutung
Lymphozele
17 (24%)
13 (19%)
12 (17%)
9 (33%)
7 (26%)
7 (26%)
0.50
0.52
0.43
51
ABOi
≤ 1:128
(n = 70)
ABOi
≥ 1:256
(n = 27)
p
Rejektionen
humoral 5 (7%) 4 (15%) 0.29
zellulär 9 (13%) 4 (15%) 0.82
Borderline 7 (10%) 8 (30%) 0.047
Outcome – Freiburger Daten
52
Chung BH, Lim JU, Kim Y, Kim JI, Moon IS, Choi BS, Park CW, Kim YS, Yang CW. Impact of the baseline anti-A/B antibody titer on the clinical outcome in ABO-incompatible kidney transplantation. Nephron Clin Pract. 2013;124(1-2):79-88.
<0.05
Outcome – Freiburger Daten
53
ABOi
≤ 1:128
(n = 70)
ABOi
≥ 1:256
(n = 27)
p
Infektionen 32 (46%) 5 (19%) 0.08
Sepsis 7 (10%) 1 (4%) 0.35
CMV-Erkrankung 5 (7%) 0 0.17
BKV-Nephropathie 5 (7%) 2 (8%) 0.97
PJ-Pneumonie 1 (1%) 0 0.54
Outcome – Freiburger Daten
54
Chung BH, Lim JU, Kim Y, Kim JI, Moon IS, Choi BS, Park CW, Kim YS, Yang CW. Impact of the baseline anti-A/B antibody titer on the clinical outcome in ABO-incompatible kidney transplantation. Nephron Clin Pract. 2013;124(1-2):79-88.
p 0.06
CMV
VZV
Outcome – Freiburger Daten
55
Zusammenfassung – „Hochtiter“ Gruppe
1. Charakteristika:
- vorzugsweise Blutgruppe A/O (v.a. A1/O)
- kürzere Dialysezeit (d.h. häufiger präemptive Tx)
- Prä-OP-Antikörper-Elimination: mehr Verfahren (10 vs. 5 IA/PP)
2. Tx-Vorbereitung:
- Kombination von IA und PP (IgM, Rebound)
- möglicherweise Akzeptanz höherer prä-OP Titer (z.B. ≤1:8 oder ≤1:16)
- ggf. Gabe von Rituximab im Vorfeld
- ggf. früherer Beginn der oralen Immunsuppression mit Rituximab
3. post-Tx:
- häufiger post-OP Verfahren
- vergleichbare Nierenfunktion zur „Niedrigtiter“ Gruppe
- Rejektionen: mehr borderline Veränderungen
möglicherweise höheres Rejektionsrisiko
- Infektionen: keine Häufung
Mitarbeitern des Transplantzentrums Freiburg
Mitarbeitern der Klinik für Innere Medizin IV
PD Dr. P. Pisarski
Dr. B. Jänigen
Fr. S. Hils (GABOiR)
Fr. cand. med. D. Dimova
Fr. Dr. E. Neumann-Haefelin
Team der Nierentransplantambulanz
Prof. Dr. G. Walz
59
Chung BH, Lim JU, Kim Y, Kim JI, Moon IS, Choi BS, Park CW, Kim YS, Yang CW. Impact of the baseline anti-A/B antibody titer on the clinical outcome in ABO-incompatible kidney transplantation. Nephron Clin Pract. 2013;124(1-2):79-88.
Chung BH, Lee JY, Kang SH, Sun IO, Choi SR, Park HS, Kim JI, Moon IS, Choi BS, Park CW, Kim YS, Yang CW. Comparison of clinical outcome between high and low baseline anti-ABO antibody titers in ABO-incompatible kidney transplantation. Ren Fail. 2011;33(2):150-8.
Protokolle anderer Zentren
61
Yang KS, Jeon H, Park Y, Jo IH, Kim JI, Moon IS, Choi BS, Park CW, Yang CW, Kim YS, Chung BH. Use of bortezomib as anti-humoral therapy in kidney transplantation. J Korean Med Sci. 2014 May;29(5):648-51.
Protokolle anderer Zentren
62
Chung BH, Lim JU, Kim Y, Kim JI, Moon IS, Choi BS, Park CW, Kim YS, Yang CW. Impact of the baseline anti-A/B antibody titer on the clinical outcome in ABO-incompatible kidney transplantation. Nephron Clin Pract. 2013;124(1-2):79-88.
Outcome – Freiburger Daten im Vergleich
Titer
at sugery
Titer
follow-up
low titer
high titer
Wilpert et al, J Clinical Apheresis 2007
2.0 ± 1.4
2.0 ± 1.3
1.5 ± 1.4
8.0 ± 4.0
(523 d)
(570 d)
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