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 Old for OldARFNHBD N391732 Patient age (yrs)67.1 ± 4,0 (56 - 74)47.7 ± 12.4 (26 - 59)51.3 ± 11.8 (28 - 70) Patient Gender (M / F)23 / 165 / 1213 / 19 Retransplants2 (5.1%)4 (23.5%)1 (3.1%) HLA-PRA > 10%4 (10.2%)3 (19.7%)1 (3.1%) Diabetes Mellitus8 (20.5%)1 (5.9%)3 (9.4%) Donor Age (yrs)68.3 ± 5.9 (49 - 79)46.9 ± 12.0 (30 - 66) 43.7  13,8 (22 - 61) Donor Gender (M / F)21 / 1811 / 627 / 5 Cold Ischemia (hrs) 16,2  5,4 (7 – 28)18,4  4,9 (8 – 30)13,7  3,5 (8 – 22) Pulsatile Machine Perf.6 (15%)010 (31%) 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 I Group II

5. ATG1,25 mg/kg/day(7days) MMF2 gr pre-op.-> 1gr BID Prednisolone500 mg intra - op-> 0.5 mg/kg-> 20 mg/day(D7) Sirolimus6 mg/day(D5, D6, D7)-> 3 mg/day -> 10-15ng/ml Basiliximab20 mg (D0 and D4) NHBD OLD for OLD, ARF Immunosuppression Protocol

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

7. 1m3m6m12m24mNadirDays s Cr1.92.01.71.81.61.586 1m3m6m12m24mNadirDays s Cr4,21.9 1.71,71.654 Serum Creatinine Results Renal Function

8. Group I Results Acute Rejection BanffnDay B-L1p243 1A4p11, 62, 66, 82 2A3p15, 16, 17 1B3p14, 47, 51 2B1p11 No Bx1p20 Basilix. 44 ATG11

9. Group II Results Acute Rejection BanffnDay 1A1p15 No Bx1p20 Basilix. 3 ATG29

10. ATG vs Basiliximab Results Acute Rejection BanffnDay 1A1p15 1B1p14 ATG (n=40) BanffnDay B-L1p243 1A4p11, 62, 66,82 2A2p16, 17 1B2p47, 51 2B1p11 No Bx1p20 Basiliximab (n=47)

11. ResultsConversion to CNI Therapy Dyslipidemia10 Chronic edemas6 Acute Rejection5 Urinary fistula3 Renal dysfunction3 Wound healing2 Thrombocitopenia2 Thrombotic microangiopathy 1 Herpetic hepatitis1

12. Group IGroup IIp Average length of stay 12.79 ± 0.725.48 ± 2.5< 0.0001 Actual sCr1.98 ± 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 ± 367659 ± 210< 0.0001 Results

13. ResultsMorbidity UTI18 Bacterial pneumonia6 Other respiratory complications5 CMV infection5 Urinary fistula5 Wound infection3 GI bleeding3 Wound hematoma3 Acute pyelonephritis2 Sepsis2 Lymphocel2 Ischemic colitis1 Rectal adenocarcinoma1 Stroke1 Aspergillus pneumonia1 Milliar tuberculosis1 HSV hepatitis1 Encephalopathy (probabily fungal) 1

14. ResultsGraft Survival Causes of Graft Failure nday Pat. death 314, 44 Rejection Stop. IS 1497 Unknown 147 Acute rejection 11 CGN 1385 Group I Causes of Graft Failure nday Pat. Death 122 Non primary function 20, 0 CGN 2 101, 793 Group II

15. ResultsPatient Survival Causes of Graft Failure nday Ischemic colitis 114 Sudden death at home 144 Rectal adenocarcinoma 1691 Group I Causes of Graft Failure nday Sepsis 122 Encephalopathy 1 892 Group II

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.