1 / 44

Understanding Vascular Rejection in Organ Transplants: Insights and Perspectives

Explore the frequency, impact, histological definitions, prognosis, treatment options, and histological findings of vascular rejection in organ transplant recipients. Learn about new detection techniques and the significance of antibodies and cross-matching.

roden
Télécharger la présentation

Understanding Vascular Rejection in Organ Transplants: Insights and Perspectives

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. A clinician’s view of Vascular Rejection D. Glotz, D. Nochy 2005

  2. Vascular Rejections Seem more and more frequent.... • 10 à 20% historically • Close to 30% or more today....

  3. Rejections St S Rej St S Rej 1970 1980 1990 2000 A changing picture… 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%

  4. Vascular Rejections A much better understanding.. • New Antibodies detection techniques • New Cross-match techniques • C4d

  5. Vascular Rejections Histological Définition • Banff: score V (IIb, III) • CCTT: individualisation

  6. Vascular Rejections Types Types • Arteriolar, glomerular, capillaries • Arteries

  7. 6 months Survival 5 years Survival Normal 20% 95% 78% Borderline 34% ACR 18% IIa 6% IIb et III 15% 78% 61% Vascular Rejections Pronostic Importance 293 Bx (J2-J35) of 382 pts Tx 1985 - 1989 Bates NDT 1999

  8. Vascular Rejections Pronostic Importance • 177 Bx of 134 transplants 1994-1996 • 31% failures if vascular rejection (58) p<0,05 • 15% failures if interstitial rejection (65) Mc Donald NDT 1999

  9. Vascular Rejections Pronostic Importance 245 Tx 1995-2002 Loucaidou Transpl 2003

  10. AHR (DSA,C4d+) ACR (DSA,C4d-) Mild AR n=18 n=30 n=30 - - + Steroid Sensitivity Antibody Sensitivity 33% 97% Graft Surv. 6 mo 77,80% 96,70% 96,70% Vascular Rejection Treatment OKT3 OKT3 232 Tx 1995-1999 Mauiyyedi JASN 2002

  11. ･ 65% men ･ Time on dialysis: 3,8 years (0,5/14) ･ Patients with PRA>0: 30% (36%) ･ Thymoglobulin, Aza, Sandimmune, steroids RENALTRANSPLANTS RENALTRANSPLANTS BROUSSAIS 1989-1993 BROUSSAIS 1987-1992 240 transplantations ･ Mean age: 42,3 years (18/64)

  12. RENALTRANSPLANTS RENALTRANSPLANTS BROUSSAIS 1989-1993 BROUSSAIS 1987-1992 Patient and Graft survival Patient and Graft survival 1 5 10 years Patient 97% 91% 82% Graft 92% 77% 58%

  13. RENAL TRANSPLANTS RENAL TRANSPLANTS BROUSSAIS 1989-1993 BROUSSAIS 1987-1992 Rejections Rejections ･ < 1% during Thymo administration ･ 22% at 6 months ･ 29% at 12 months ･ of which 81% were Steroid-sensitive ･ 10% of recurrent rejections

  14. 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

  15. Vascular Rejections Histology • 38% G3, only 24% G0 • 71% I1 • 59% T1 or T0 • 38% V3, 63% V2-V3

  16. 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

  17. Vascular Rejections 100% 90% 80% 70% 60% PATIENT 50% GRAFT 40% 30% 20% 10% 0% 0 1 2 3 4

  18. Vascular Rejections Repeat biopsies (67% of patients) • 100% reversal • No recurrent rejections • Extensive fibrosis

  19. Vascular Rejections 100% 90% 80% 70% 60% PATIENT 50% GRAFT 40% 30% 20% 10% 0% 0 10 20 30 40

  20. Vascular Rejections A much better understanding.. • New Antibodies detection techniques • New Cross-match techniques • C4d

  21. Our series 76% Glomerulitis 46% 10% 0,01 59% T0-T1 50% 5% 0,02 41% T2-T3 50% 95% 0,02 37% V0-V1 42% 90% 0,01 63% V2-V3 58% 10% 0,01 Graft loss 12 (50%) 3 (15%) 0,025 Antibody associated Rejections Histology Abs + (n=24) Abs - (n=20) p 44/459 Tx 1987-1994 Trpkov Transpl 1996

  22. C4d associated to the existence of DSA • Unselected biopsies • Specificity: 93% • Sensitivity: 31% • P. Positive Value : 87% Bohmig JASN 2002

  23. 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

  24. C V 58 35 C4d+ 31% 46% C4d- 69% 54% C V Graft loss 58 35 C4d+ 38% 33% 44% C4d- 7% 5% 11% p<0,0001 p<0,001 p<0,05 C4d positive Rejections Pronostic Importance Hertzenberg JASN 2002

  25. Humoral Rejection Définition Définition • Histological Lesions • NTA • CPT, glom, thromboses • Arteritis • C4d positive • Donor specific Antibodies

  26. 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

  27. 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

  28. 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%

  29. 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%

  30. Abs + (n=24) Abs - (n=20) Trpkov Transpl 1996 Peak PRA 36,50% 24,50% NS Pre-Tx PRA 11,30% 14,70% NS Re-Tx 50% 10% p<0,01 AHR (DSA,C4d+) ACR (DSA,C4d-) Mild AR Crespo, Transpl 2001 n=18 n=30 n=30 Peak pre-Tx PRA 56,50% 3% 3% Re-Tx 38,90% 6,70% 6,70% Who’s at risk of Humoral Rejection?

  31. 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%

  32. Humoral Rejection Treatment • IVIg • IVIg/Plasmapheresis

  33. Humoral Rejection Treatment IVIg Treatment • 7 patients • 6 resistant to anti-lymphocyte antibodies • 7 short term success (<6months) Jordan, Transpl 1998

  34. Humoral Rejection Treatment IVIg Treatment • 17 patients • 13 rejections StR, 4 AbR • Patient Survival 18 months: 94% • Graft Survival 18 months: 71% Luke, Transpl 2001

  35. Humoral Rejection Treatment IVIg/PP treatment • 3 patients • AHR with DSA • 100% success Montgomery, Transpl 2000

  36. Humoral Rejection Treatment IVIg/PP treatment • 16 patients • 100% StR, 50% AbR • Graft survival 1 year: 81% (84%) Rocha, Transpl 2003

  37. 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

  38. 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…. 2 periods in time, 2 definitions of rejection, 2 treatments…

  39. Humoral Rejection D.S.A. IVIg/PP Vascular Rejection « Cellular » Ab Anti-Lymphocytes Vascular Rejections Rejets Vasculaires

More Related