Impact of Rituximab (RTx) Induction and Living Donation on Immunoregulation and Virus Control in Renal Transplantation

This project comprises immunological and virological analyses within a prospective clinical study of Rituximab (Rtx)-treated blood group incompatible living donor (LD) renal transplant recipients compared to blood group compatible LD recipients without Rtx induction, and of living donor compared to deceased donor renal transplant recipients treated with tacrolimus (Tacr)/mycophenolate sodium (MPS). Aim of this project is to assess short- and long-term effects of immunosuppressive therapy (Rtx induction) and of living donation on immunological and histological parameters of graft outcome and on viral replication (BK virus (BKV), JC virus (JCV), cytomegalovirus (CMV), Epstein Barr virus (EBV)) with the potential to improve long-term graft outcome and to enable risk estimation of virus disease.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* De-novo kidney transplantation
* Deceased donors (blood group compatible) and living donors (blood group incompatible / blood group compatible)
* First, second and third renal transplants
* Immunized and non-immunized graft recipients
* Age of recipients 18 years or older
* Negative pregnancy test before transplantation

Exclusion Criteria:

* Contra-indications to use Tacr and MPS, respectively
* Contra-indications to use Rtx in the group of ABOi LD transplants
* Chronic hepatitis B, C or HIV infection
* Recurrent infectious disease
* Previous hepatitis B, if no prophylactic antiviral therapy is used
* Previous tuberculosis
* Hemoglobin\<8,5g/dl, thrombocytes\<80.000/ul or leucocytes\<3000/ul
* Previous vaccination with a living vaccine \<4 weeks pretransplant
* Significant enterogastric disease such as diverticulitis (contra-indicates MPS treatment)
* Children and adolescents (age less than 18 years)
* Pregnancy and breast-feeding women
* Refusal of an effective contraception in women capable of bearing children
* Combined transplantations such as simultaneous islet/kidney transplants

• BACKGROUNDHackstein H, Renner FC, Bohnert A, Nockher A, Frommer T, Bein G, Weimer R. Dendritic cell deficiency in the blood of kidney transplant patients on long-term immunosuppression: results of a prospective matched-cohort study. Am J Transplant. 2005 Dec;5(12):2945-53. doi: 10.1111/j.1600-6143.2005.01101.x. PMID 16303009
• BACKGROUNDSadeghi M, Daniel V, Weimer R, Wiesel M, Hergesell O, Opelz G. Differential early posttransplant cytokine responses in living and cadaver donor renal allografts. Transplantation. 2003 Apr 27;75(8):1351-5. doi: 10.1097/01.TP.0000063706.52369.ED. PMID 12717229
• BACKGROUNDStaak A, Renner F, Suesal C, Dietrich H, Rainer L, Kamali-Ernst S, Ernst W, Padberg W, Opelz G, Weimer R. Immunoglobulin induction therapy in renal transplant recipients: Effects on immunoglobulin and regulatory antibody levels. Transplant Proc. 2006 Dec;38(10):3483-5. doi: 10.1016/j.transproceed.2006.10.041. PMID 17175311
• BACKGROUNDWeimer R, Melk A, Daniel V, Friemann S, Padberg W, Opelz G. Switch from cyclosporine A to tacrolimus in renal transplant recipients: impact on Th1, Th2, and monokine responses. Hum Immunol. 2000 Sep;61(9):884-97. doi: 10.1016/s0198-8859(00)00152-x. PMID 11053632
• BACKGROUNDWeimer R, Mytilineos J, Feustel A, Preiss A, Daniel V, Grimm H, Wiesel M, Opelz G. Mycophenolate mofetil-based immunosuppression and cytokine genotypes: effects on monokine secretion and antigen presentation in long-term renal transplant recipients. Transplantation. 2003 Jun 27;75(12):2090-9. doi: 10.1097/01.TP.0000058808.37349.23. PMID 12829918
• BACKGROUNDWeimer R, Staak A, Susal C, Streller S, Yildiz S, Pelzl S, Renner F, Dietrich H, Daniel V, Rainer L, Kamali-Ernst S, Ernst W, Padberg W, Opelz G. ATG induction therapy: long-term effects on Th1 but not on Th2 responses. Transpl Int. 2005 Feb;18(2):226-36. doi: 10.1111/j.1432-2277.2004.00047.x. PMID 15691277