a clinician’s view of vascular rejection
DESCRIPTION
A clinician’s view of Vascular Rejection. D. Glotz, D. Nochy 2005. Vascular Rejections. Seem more and more frequent. •. 10 à 20% historically. •. Close to 30% or more today. Rejections. St S Rej. St S Rej. 1970. 1980. 1990. 2000. A changing picture…. 90%. 80%. 70%. 60%. 50%. - PowerPoint PPT PresentationTRANSCRIPT
Seem more and more frequent....
• 10 à 20% historically
• Close to 30% or more today....
Vascular Rejections
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
1970 1980 1990 2000
A changing picture…
St S Rej
St S Rej
Rejections
A much better understanding..
• New Antibodies detection techniques
• New Cross-match techniques
• C4d
Vascular Rejections
Vascular Rejections
Pronostic Importance
293 Bx (J2-J35) of 382 pts Tx 1985 - 1989
Bates NDT 1999
6 months Survival 5 years Survival
Normal 20%
95% 78%Borderline 34%
ACR 18%
IIa 6%
IIb et III 15% 78% 61%
• 177 Bx of 134 transplants 1994-1996• 31% failures if vascular rejection (58)• 15% failures if interstitial rejection (65)
p<0,05
Mc Donald NDT 1999
Vascular Rejections
Pronostic Importance
Vascular Rejection Treatment
- - +
33% 97%
AHR (DSA,C4d+) ACR (DSA,C4d-) Mild AR
n=18 n=30 n=30
Steroid Sensitivity
Antibody Sensitivity
Graft Surv. 6 mo 77,80% 96,70% 96,70%
232 Tx 1995-1999
Mauiyyedi JASN 2002
OKT3OKT3
RENALTRANSPLANTS BROUSSAIS 1987-1992RENALTRANSPLANTS BROUSSAIS 1989-1993
240 transplantations・Mean age: 42,3 years (18/64)・ 65% men
・Time on dialysis: 3,8 years (0,5/14)
・ Patients with PRA>0: 30% (36%)
・Thymoglobulin, Aza, Sandimmune, steroids
RENALTRANSPLANTS BROUSSAIS 1987-1992RENALTRANSPLANTS BROUSSAIS 1989-1993
1 5 10
Patient 97% 91% 82%
Graft 92% 77% 58%
Patient and Graft survivalPatient and Graft survival
years
RENAL TRANSPLANTS BROUSSAIS 1987-1992RENAL TRANSPLANTS BROUSSAIS 1989-1993
RejectionsRejections
・ < 1% during Thymo administration・ 22% at 6 months・ 29% at 12 months
・ of which 81% were Steroid-sensitive・ 10% of recurrent rejections
Vascular Rejections
17 Vascular rejections
•7,1% of all patients•76% steroid-resistant•4 treated with OKT3 as first-line TT •28% of all rejections
Vascular Rejections
17 Vascular rejections
•47% sensitized patients•82% first episode of rejection•Delay Tx-rejection: 89 days (53% 35 days, 47% >6 months)•Creatinin at rejection: 408 µM/l•Reversal: 75%
All treated with Steroid pulses and OKT3
Repeat biopsies (67% of patients)
Vascular Rejections
•100% reversal•No recurrent rejections•Extensive fibrosis
A much better understanding..
• New Antibodies detection techniques
• New Cross-match techniques
• C4d
Vascular Rejections
Antibody associated Rejections
HistologyAbs + (n=24) Abs - (n=20) p
Glomerulitis 46% 10% 0,01
T0-T1 50% 5% 0,02
T2-T3 50% 95% 0,02
V0-V1 42% 90% 0,01
V2-V3 58% 10% 0,01
Graft loss 12 (50%) 3 (15%) 0,025
44/459 Tx 1987-1994 Trpkov Transpl 1996
76%
59%
41%
37%
63%
Our series
associated to the existence of DSA
• Unselected biopsies• Specificity: 93%• Sensitivity: 31%• P. Positive Value : 87%
Bohmig JASN 2002
C4d
associated to humoral rejection with DSA
• 232 pts Tx 1995 - 1999• 67 pts with rejet<3 months, IF and sérum• 30% C4d + (20/67)• 30% AHR, 45% AHR+ACR• 96% with DSA
Mauiyyedi JASN 2002
C4d
C V
58 35
C4d+ 31% 46%
C4d- 69% 54%
Graft loss C V58 35
38% C4d+ 33% 44%
7% C4d- 5% 11%
p<0,0001 p<0,001 p<0,05
Hertzenberg JASN 2002
C4d positive Rejections
Pronostic Importance
Humoral Rejection
DéfinitionDéfinition• Histological Lesions
• NTA
• CPT, glom, thromboses
• Arteritis• C4d positive• Donor specific Antibodies
Humoral Rejection
The Pompidou experience 1999-2004
•237 transplants•25% immunized/re-transplant patients•Thymoglobulin, Neoral, Cellcept, steroids•14,6% Rejections•9,7% Humoral Rejections
Humoral Rejection
The Pompidou experience 1999-2004
•23 patients, 56 Biopsies of A.H.R.•78% in immunized patients•Delay Tx-A.H.R. 16 days in 87% of cases•Creatinin at rejection 290 µM/l
Humoral Rejection
C4d and D.S.A. at 1st Biopsy
•C4d +, D.S.A. + 52,2% •C4d +, D.S.A. - 30,5%•C4d ?, D.S.A. + 8,7%•C4d -, D.S.A. - 8,7%
Humoral Rejection
Histological findings at 1st biopsy
•Glomerular neutrophils 78,6%•PTC dilatation 83,9%•PTC neutrophils 39,1%•Acute Tubular damage 65,2%•Glomerular TMA 30,4%•G1-3 94,6%•V1-2 56,5%
Who’s at risk of Humoral Rejection?
AHR (DSA,C4d+) ACR (DSA,C4d-) Mild AR
n=18 n=30 n=30
Peak pre-Tx PRA 56,50% 3% 3%
Re-Tx 38,90% 6,70% 6,70%
Crespo, Transpl 2001
Trpkov Transpl 1996
Abs + (n=24) Abs - (n=20)
Peak PRA 36,50% 24,50% NS
Pre-Tx PRA 11,30% 14,70% NS
Re-Tx 50% 10% p<0,01
Who’s at risk of Humoral Rejection?
The Pompidou experience 1999-2004
•30% A.H.R. in immunized vs 3% in non immunized patients
•D.S.A. pre-Tx (ELISA): 65,2%
•Historical positive crossmatch: 43,5%
IVIg Treatment
• 7 patients
• 6 resistant to anti-lymphocyte antibodies
• 7 short term success (<6months)
Jordan, Transpl 1998
Humoral Rejection Treatment
• 17 patients
• 13 rejections StR, 4 AbR
• Patient Survival 18 months: 94%
• Graft Survival 18 months: 71%Luke, Transpl 2001
IVIg Treatment
Humoral Rejection Treatment
IVIg/PP treatment
• 3 patients
• AHR with DSA
• 100% success
Montgomery, Transpl 2000
Humoral Rejection Treatment
• 16 patients
• 100% StR, 50% AbR
• Graft survival 1 year: 81% (84%)
Rocha, Transpl 2003
IVIg/PP treatment
Humoral Rejection Treatment
Humoral Rejection
The Pompidou experience 1999-2004
•Treatment with IVIg high dose and Steroid pulses•75% success, no deaths•Mean Follow-up 36 ± 21 months•Last creatinin 193 µM/l
2 periods in time, 2 definitions of rejection, 2 treatments…
Period 1989-1993 1999-2004
Type of rejection "Vascular" "Humoral"
% immunised patients 30% 25%
% rejection 29% 14,30%
% V/AHR 7,10% 9,70%
% V/AHR in rejections 25% 68%
% Immunized pats/rej 47% 78%
Delay Tx-rejection 35 days 16 days
Creatinin at rejection 406 µM/l 290µM/l
Treatment OKT3 IVIg
Success rate short term 75% 75%
And the same success rate….