Polyomavirus Infections
Conditions
Keywords
kidney transplantation, polyoma virus associated transplant nephropathy, tacrolimus, mycophenolate mofetil, everolimus, cyclosporin A, BK virus PCR, viruria screening, BK polyomavirus, immunosuppression
Brief summary
The aim of this study is to characterize and evaluate risk factors of polyomavirus nephropathy (PVN) including the impact of three immunosuppressive regimens.
Detailed description
Polyomavirus nephropathy (PVN) is an emerging cause of renal transplant loss. Until now the risk factors of PVN are poorly understood. Tacrolimus (Tacr) and mycophenolate mofetil (MMF) are thought to be associated with a higher risk of developing PVN. However, the way in which Tacr or MMF might enhance the susceptibility for PVN remains largely unknown. In this prospective study we will analyze whether differences in immune-reactivity patterns (Th1, Th2, B cell and monocyte responses, sCD30, immunoregulatory antibodies) of renal transplant patients induced by different immunosuppressive regimens (cyclosporine A \[CsA\]/MMF, Tacr/MMF, Tacr/MMF with conversion to Tacr/Everolimus \[ERL\]) or by cytokine promoter gene polymorphisms may account for the different risks of developing PVN. Comparison(s): renal transplant recipients stratified according to their relative immunological risk (group 1: low risk (primary recipients without pre-immunization \[PRA \< 5%\]); group 2: moderate risk (group 2a: primary recipients with low pre-immunization \[PRA 6-20%\]; group 2b: re-transplanted patients); group 3: very high risk (re-transplanted patients with a history of vascular rejection or recipients of a first graft with high pre-immunization \[PRA \> 20%\]) randomized to be treated with one of three immunosuppressive regimens (CsA/MMF, Tacr/MMF, Tacr/MMF with subsequent conversion to Tacr/ERL).
Interventions
DRUGCiclosporin and Mycophenolate-mofetil
according to the Giessen protocol
DRUGTacrolimus and Mycophenolate-mofetil
according to Giessen protocol
DRUGTacrolimus and Mycophenolate-mofetil with change from Mycophenolate-mofetil to Everolimus
according to Giessen protocol
Sponsors
Heidelberg University
Hoffmann-La Roche
Astellas Pharma Inc
Novartis
University of Giessen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Cadaver kidney and living donor kidney transplant recipients * Primary, secondary, and tertiary transplant recipients * Pre-immunized and not pre-immunized transplant recipients * Age \> 18 years
Exclusion criteria
* Contraindications against administration of one of the four study drugs * History of severe gastrointestinal morbidity * Age \< 18 years * Pregnant or breast feeding women * Rejection of effective contraceptive methods with young women * Combined kidney and islet cell transplantation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| urine polyomavirus concentration within the first two years post-transplant | 2 years posttransplant |
| incidence of polyoma viremia | 2 years posttransplant |
| incidence of polyomavirus associated transplant nephropathy (PVN) | 2 years posttransplant |
Secondary
| Measure | Time frame |
|---|---|
| comparison of urine cytology and polymerase chain reaction (PCR) quantitative data regarding diagnosis of PVN | 2 years posttransplant |
| patients' and grafts' survival | 2 years posttransplant |
| side effects of immunosuppressive drugs | 2 years posttransplant |
| predictive value of immune parameters prognostically relevant for acute or chronic rejection | 2 years posttransplant |
| incidence of acute rejections | 2 years posttransplant |
| transplant function 1 and 2 years post-transplant | 2 years posttransplant |
Countries
Germany
Outcome results
None listed