Th1, Th2 and Monokine Responses as Risk Factors of Renal Transplant Rejection - Full Text View

Purpose

Chronic transplant rejection remains the main cause of late kidney graft loss. We showed previously that patients with pretransplant CD4 helper defects and low in-vitro IL-10 responses demonstrated an extremely low risk of acute rejection and a significantly better 1- and 3-year graft function whereas pretransplant Th1 responses were not predictive (Weimer R et al. 1996 and 1998). In liver transplant recipients, we found CD4 helper function and in-vitro IL-10 responses significantly decreased compared to CsA-treated patients (Zipperle et al. 1997). If the same effect will be demonstrated in renal transplant recipients, Tacrolimus (Tacr) treatment might result in enhanced graft survival compared to CsA, when CD4 helper function and in-vitro IL-10 responses of the individual patient are elevated. Other studies of our group suggest a beneficial role of enhanced T-suppressor activity and of an IL-6 independent B cell/monocyte defect in the maintenance of long-term stable graft function, whereas enhanced monokine secretion (TNF-a, GM-CSF, IL-6) was found in chronic rejection (Weimer et al. 1990, 1992, 1994, 1998).

In the current randomized prospective study we will analyze the impact of CsA versus Tacr and of MMF versus azathioprine on Th1, Th2 and monokine responses and their predictive value regarding occurrence of acute and chronic rejection. With a proposed follow-up of 5 years this study might enable a patient-tailored immunosuppressive therapy resulting in prolonged graft survival.

Condition	Intervention
Renal Failure, Chronic	Procedure: Kidney transplantation Drug: cyclosporine A Drug: tacrolimus Drug: azathioprine Drug: mycophenolate mofetil

Study Type:	Observational
Study Design:	Observational Model: Defined Population Primary Purpose: Screening Time Perspective: Longitudinal Time Perspective: Prospective
Official Title:	Role of Th1, Th2 and Monokine Responses as Risk Factors of Acute and Chronic Renal Transplant Rejection – Impact of Different Immunosuppressive Protocols

Resource links provided by NLM:

MedlinePlus related topics: Kidney Transplantation

Drug Information available for: Azathioprine Mycophenolic acid Mycophenolate sodium Azathioprine Sodium Cyclosporine Tacrolimus Mycophenolate mofetil hydrochloride Mycophenolate mofetil

U.S. FDA Resources

Further study details as provided by University of Giessen:

Enrollment:	84
Study Start Date:	January 1998
Study Completion Date:	January 2006

Show Detailed Description

Eligibility

Ages Eligible for Study:	14 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Renal transplant recipients in the Giessen renal transplant unit

Exclusion Criteria:

Contraindications against blood-taking (anemia with hemoglobin<9.5 g/l, hypotension etc.)
No informed consent by the patient

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00150891

Locations

Germany
Department of Internal Medicine, University of Giessen
Giessen, Germany, D-35392

Sponsors and Collaborators

University of Giessen

University of Heidelberg

Astellas Pharma Inc

Novartis

Fresenius AG

Hoffmann-La Roche

Biotest

Investigators

Principal Investigator:

Rolf Weimer, Prof. Dr.

Department of Internal Medicine, University of Giessen, Germany

More Information

Publications:

Weimer R, Streller S, Staak A, Heilke M, Li D, Dietrich H, Daniel V, Feustel A, Rainer L, Zinn S, Friemann S, Ernst W, Grimm H, Padberg W, Zimmermann T, Opelz G. Effects of three immunosuppressive regimens on CD4 helper function, B cell monocyte and cytokine responses in renal transplant recipients: 4-month follow-up of a prospective randomized study. Transplant Proc. 2002 Sep;34(6):2377-8. No abstract available.

Weimer 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.

Weimer R, Susal C, Yildiz S, Streller S, Pelzl S, Staak A, Renner F, Dietrich H, Daniel V, Feuring E, Kamali-Ernst S, Ernst W, Padberg W, Opelz G. sCD30 and neopterin as risk factors of chronic renal transplant rejection: impact of cyclosporine A, tacrolimus, and mycophenolate mofetil. Transplant Proc. 2005 May;37(4):1776-8.

Weimer R, Susal C, Yildiz S, Staak A, Pelzl S, Renner F, Dietrich H, Daniel V, Kamali-Ernst S, Ernst W, Padberg W, Opelz G. Post-transplant sCD30 and neopterin as predictors of chronic allograft nephropathy: impact of different immunosuppressive regimens. Am J Transplant. 2006 Aug;6(8):1865-74. Epub 2006 Jun 9.

Weimer 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.

Weimer 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.

Weimer R, Zipperle S, Daniel V, Carl S, Staehler G, Opelz G. Superior 3-year kidney graft function in patients with impaired pretransplant Th2 responses. Transpl Int. 1998;11 Suppl 1:S350-6.

Zipperle S, Weimer R, Golling M, Daniel V, Otto G, Opelz G. Impaired T-cell IL-10 secretion and CD4 helper function in liver transplant patients treated with tacrolimus. Transplant Proc. 1997 Feb-Mar;29(1-2):1079-80. No abstract available.

Weimer R, Zipperle S, Daniel V, Carl S, Staehler G, Opelz G. Pretransplant CD4 helper function and interleukin 10 response predict risk of acute kidney graft rejection. Transplantation. 1996 Dec 15;62(11):1606-14.

Weimer R, Zipperle S, Daniel V, Pomer S, Staehler G, Opelz G. IL-6 independent monocyte/B cell defect in renal transplant recipients with long-term stable graft function. Transplantation. 1994 Jan;57(1):54-9.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Weimer R, Deisz S, Dietrich H, Renner F, Bödeker RH, Daniel V, Kamali-Ernst S, Ernst W, Padberg W, Opelz G. Impact of maintenance immunosuppressive regimens--balance between graft protective suppression of immune functions and a near physiological immune response. Transpl Int. 2011 Jun;24(6):596-609. Epub 2011 Mar 14.

ClinicalTrials.gov Identifier:	NCT00150891 History of Changes
Other Study ID Numbers:	NTx-prosp-001
Study First Received:	September 6, 2005
Last Updated:	May 8, 2007
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Giessen:

Th1
Th2
B cell
monokines

kidney transplantation
acute rejection
chronic rejection

Additional relevant MeSH terms:

Kidney Failure, Chronic
Renal Insufficiency
Renal Insufficiency, Chronic
Kidney Diseases
Urologic Diseases
Azathioprine
Cyclosporins
Cyclosporine
Mycophenolate mofetil
Tacrolimus
Mycophenolic Acid
Antimetabolites
Molecular Mechanisms of Pharmacological Action

Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on May 16, 2013