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Oppenheimer F, Saval N, Gutierrez A, Cam pistol JM, Cofàn F, Esforzado N, Torregrosa JV, Ricart MJ

Experience with Calcineurin Inhibitor-Free Immunosuppression in Kidney Transplantation with Marginal Donors. Oppenheimer F, Saval N, Gutierrez A, Cam pistol JM, Cofàn F, Esforzado N, Torregrosa JV, Ricart MJ Renal Transplant Unit Hospital Clínic – Universitat de Barcelona Barcelona -Spain.

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Oppenheimer F, Saval N, Gutierrez A, Cam pistol JM, Cofàn F, Esforzado N, Torregrosa JV, Ricart MJ

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  1. Experience with Calcineurin Inhibitor-Free Immunosuppression in Kidney Transplantation with Marginal Donors Oppenheimer F, Saval N, Gutierrez A, Cam pistol JM, Cofàn F, Esforzado N, Torregrosa JV, Ricart MJ Renal Transplant Unit Hospital Clínic – Universitat de Barcelona Barcelona -Spain

  2. Introduction Kidneys from elderly donors, non-heart-beating donors (NHBD), or acute renal failure (ARF) usually show prolonged delayed graft function (DGF). DGF is associated with a higher risk of acute rejection and chronic graft nephropathy. The use of CNI-free immunosuppression in kidney transplant recipients from marginal donors may reduce the risk of DGF, improve renal function recovery and prevent long-term consequences of nephrotoxicity.

  3. Objective To assess the potential benefit of a strong but non-nephrotoxic (CNI-free) immunosuppression regimen for kidney transplant recipients with a high risk of DGF

  4. Patients and Methods All consecutive kidney transplants between November 2002 and June 2005 with one of the following characteristics : - NHBD - Donors with ARF (sCr > 2 mg/dl) - Donor age > 60 yrs and Patient age > 60 yrs old Exclusion: - Living Donors - Immunological high-risk patients Group II Group I

  5. Immunosuppression Protocol MMF 2 gr pre-op. - > 1gr BID Prednisolone 500 mg intra - op - > 0.5 mg/kg - > 20 mg/day (D7) Sirolimus 6 mg/ day (D5, D6, D7) - > 3 mg/ day - > 10 - 15 ng /ml ATG 1,25 mg/kg/ day (7 days ) NHBD , ARF OLD for OLD Basiliximab 20 mg ( D0 and D4)

  6. Results Recovery of Graft Function Incidence of Delayed Graft Function

  7. Results Renal Function Serum Creatinine

  8. Banff n Day B-L 1p 243 1A 4p 11, 62, 66, 82 2A 3p 15, 16, 17 1B 3p 14, 47, 51 2B 1p 11 No Bx 1p 20 Results Acute Rejection Group I Basilix. 44 ATG 11

  9. Banff n Day 1A 1p 15 No Bx 1p 20 Results Acute Rejection Group II Basilix. 3 ATG 29

  10. Basiliximab (n=47) ATG (n=40) Banff n Day B-L 1p 243 1A 4p 11, 62, 66,82 2A 2p 16, 17 1B 2p 47, 51 2B 1p 11 No Bx 1p 20 Banff n Day 1A 1p 15 1B 1p 14 Results Acute Rejection ATG vs Basiliximab

  11. Results Conversion to CNI Therapy Dyslipidemia 10 Chronic edemas 6 Acute Rejection 5 Urinary fistula 3 Renal dysfunction 3 Wound healing 2 Thrombocitopenia 2 Thrombotic microangiopathy 1 Herpetic hepatitis 1

  12. Results Group I Group II p Average length of stay12.79 ± 0.7 25.48 ± 2.5 < 0.0001 Actual sCr 1.98 ± 0.1 1.73 ± 0.1 0.0004 Actual CrCr 57.88 ± 3.6 67.9 ± 5.0 0.465 Actual proteinuria (mg/24hr) 1048 ± 367 659 ± 210 < 0.0001

  13. Results Morbidity UTI 18 Bacterial pneumonia 6 Other respiratory complications 5 CMV infection 5 Urinary fistula 5 Wound infection 3 GI bleeding 3 Wound hematoma 3 Acute pyelonephritis 2 Sepsis 2 Lymphocel 2 Ischemic colitis 1 Rectal adenocarcinoma 1 Stroke 1 Aspergillus pneumonia 1 Milliar tuberculosis 1 HSV hepatitis 1 Encephalopathy (probabily fungal) 1

  14. Group I Group II Causes of Graft Failure n day Pat. death 3 14, 44 Rejection Stop. IS 1 497 Unknown 1 47 Acute rejection 1 1 CGN 1 385 Causes of Graft Failure n day Pat. Death 1 22 Non primary function 2 0, 0 CGN 2 101, 793 Results Graft Survival

  15. Group I Group II Causes of Graft Failure n day Ischemic colitis 1 14 Sudden death at home 1 44 Rectal adenocarcinoma 1 691 Causes of Graft Failure n day Sepsis 1 22 Encephalopathy 1 892 Results Patient Survival

  16. Summary Recovery of graft function was excellent, with a remarkable low rate of DGF in recipients from elderly donors. Despite the high rate of DGF in recipients from NHBD, the incidence of acute rejection was low. Excellent patient and graft survival was achieved, comparable to standard transplant population. Infections and sirolimus side effects are the major limiting factors of this regimen.

  17. Conclusion This pilot study suggests that ATG or Basiliximab in combination with sirolimus and MMF provides effective immunosuppression for recipients of marginal kidney transplants .

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