Acute Rejection of Renal Transplant, Bone Disease, Cardiovascular Risk Factors, Death, Graft Failure, HLA Antibody Production, Infections, Non-HLA Antibody Production, Post Transplant Diabetes Mellitus, Quality of Life
Conditions
Keywords
elderly kidney transplant recipient, registry, tacrolimus once daily
Brief summary
SENIOR transplant Registry European transplant registry of senior renal transplant recipients (above the age of 65 years) receiving initial immunosuppression with tacrolimus once daily, mycophenolate and steroids to investigate long term outcomes on an observational basis.
Detailed description
The purpose of the registry is to establish data on the long-term outcome of elderly renal transplant recipients receiving an initial standard immunosuppression with tacrolimus once daily, mycophenolate and steroids The objectives of this registry are to investigate the long-term course of renal transplantation in the elderly European population (≥65 years) under immunosuppression with tacrolimus once daily, mycophenolate and steroids in order to better define risk factors for patient death and graft loss and predictors for favourable outcomes in this growing population. For this purpose, the SENIOR transplant registry will be implemented to collect data on graft loss, death, renal function, quality of life and biopsy proven acute rejections (BPAR), analyze common complications such as severe infections, opportunistic infections (CMV and/or BKV viremia), malignancies, cardiovascular events, and hospitalisations in a large population of European senior renal allograft recipients. In addition, type and severity of rejections (Banff-grade, steroid resistant rejections, antibody-mediated rejections, antibody-treated rejections, recurrent rejections), development of circulating donor specific antibodies (DSA), cardiovascular risk factors (such as diabetes, development of posttransplant diabetes (PTDM), hypertension), renal function (as estimated by CKD-EPI), and proteinuria will be longitudinally assessed in parallel to immunosuppressive doses and drug levels. The registry will focus on common side effects of immunosuppressive therapy (such as leucopenia, anemia), treatment patterns and reasons for treatment changes. Finally, a prospective analysis of quality of life including the burden of medication in elderly transplant recipients is planned. All recipients (≥65 years) of a kidney transplant who are willing to participate in the European SENIOR-Registry may enter the registry prior to transplantation if they are fulfilling all in- and none of the exclusion criteria and receive the intended initial immunosuppression consisting of tacrolimus once daily (Advagraf, initially adjusted to trough blood levels of ≥5ng/ml), mycophenolate (either ≥1.0g/day Mycophenolate Mofetil (MMF) or ≥720mg/d enteric-coated Mycophenolate Sodium (EC-MPS)) and Steroids. There will be 12 study visits during the 10 year period. Except for quality of life questionnaires there are no study specific procedures planned. Only data will be recorded which anyway will be recorded in clinical routine. The study population will consist of a representative group of approximately 1000 senior (≥65 years) kidney transplant patients, who receive a renal allograft and an initial standard triple immunosuppression (tacrolimus once daily (Advagraf), mycophenolate (either ≥1.0g/day Mycophenolate Mofetil (MMF) or ≥720mg/d enteric-coated Mycophenolate Sodium (EC-MPS)) and steroids. The patients will be recruited from approximately 42 transplant centers in Europe.
Interventions
DRUGTacrolimus once daily (Advagraf)
Antibody induction by antithymocyte Globulin (ATG) or Basiliximab possible but not mandatory
Sponsors
Dr. med. univ. L. J. Lehner
Charite University, Berlin, Germany
ERA-EDTA
DESCARTES Working Group On Transplantation
European Kidney Transplant Association (EKITA)
Klemens Budde
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males or females, aged ≥65 years * Patients who received a renal allograft * Patients who are willing and able to participate in the study and from whom written informed consent has been obtained * Patients on an intended standard triple therapy with tacrolimus once daily (Advagraf with trough level ≥5ng/ml) in combination with mycophenolate (either ≥1.0g/day MMF or ≥720mg/d EC-MPS) and Steroids (≥5mg prednisolone or equivalent) * Patient must have received primary or secondary renal allograft from a blood group compatible donor (either deceased or living) * Patients with low to standard immunological risk, who had a PRA 20% (PRA testing according to center's practice) or no known donor specific antibodies at transplantation
Exclusion criteria
* Multi-organ recipients (solid organ or bone marrow) * More than secondary renal allograft recipients * Blood group A,B,O-incompatible allografts * Documented presence of donor specific antibodies (DSA) * Panel reactive antibody (PRA) \>20% prior to transplantation (PRA testing according to center's practice) * Patients having received any other induction therapy than Basiliximab or depleting polyclonal antithymocyte antibodies (ATG) (e.g. OKT3, Campath) * Patients receiving Sirolimus, Everolimus, Azathioprine, Belatacept or Cyclophosphamide within 3 months prior to or at enrolment * History of alcohol or drug abuse with less than 6 months of sobriety * Patient with any condition that may affect absorption of immunosuppressives, (e.g. severe diarrhoea, gastrectomy, active peptic ulcer disease or clinically significant diabetic gastroenteropathy) or tacrolimus metabolism (e.g. liver cirrhosis) * Patient with mental dysfunction or inability to cooperate within the study * Patients who have been institutionalized by official or court order
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient survival | From date of transplantation until the date of death from any cause, assessed up to 10 years | — |
| Renal graft survival | From date of transplantation until the date of documented graft failure (need for permanent dialysis, explantation of the graft, retransplantation) or date of death from any cause, whichever came first, assessed up to 10 years | — |
| Biopsy proven acute rejection (BPAR) | Time of transplantation to date of first BPAR and consecutive BPARs, assessed up to 10 years | Type of rejection according to BANFF 2013 classification |
| Development of anti-HLA antibodies | Time of transplantation to date of first detection of any HLA antibodies, assesments are month 3 and year 1,3,5,7 and 10 in the central laboratory and all in all up to 10 years locally | type of antibodies (by HLA class and specificity), outcome after antibody production |
| Renal graft function by estimated glomerular Filtration rate (eGFR) by CKD-EPI) calculation | Assesment of renal graft function over time up to 10 years or graft failure or death, whichever comes first | Change of creatinine from baseline to the discrete observational visits, Calculation of eGFR (CKD-EPI) and eGFR slope |
| Development of non-HLA antibodies | Time of transplantation to date of first detection of any HLA antibodies, assesments are month 3 and year 1,3,5,7 and 10 in the central laboratory and all in all up to 10 years locally | type of antibodies, outcome after antibody production |
| Development of donor specific antibodies (DSA) | Time of transplantation to date of first detection of any HLA antibodies, assesments are month 3 and year 1,3,5,7 and 10 in the central laboratory and all in all up to 10 years locally | type of antibodies (by HLA class and specificity), outcome after antibody production |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| non-fatal myocardial infarction | from time of transplantation to the date of the event for up to 10 years, whichever comes first | number and type of events |
| Hospitalisations | from time of transplantation up to 10 years | Incidence of hospitalisations, reasons and length of hospitalisations |
| Infections in general | from time of transplantation up to 10 years | Incidence of infections and type of infections |
| Cytomegalovirus (CMV) disease | from time of transplantation up to 10 years | Incidence, defined by symptomatic CMV infection (including pulmonary and intestinal infections) |
| CMV infection | from time of transplantation up to 10 years | Incidence, Defined by nucleic acid testing (NAT) in blood |
| BKV (BK-Virus) infection | from time of transplantation up to 10 years | Incidence; Def: NAT testing in urine and blood or by biopsy staining |
| Incidence of kidney biopsies and suspected rejections | from time of transplantation for up to 10 years | Incidence (number) of kidney biopsies and suspected rejections |
| Malignancies | from time of transplantation up to 10 years | Incidence, types of malignancies |
| Post transplant diabetes mellitus | from time of transplantation up to 10 years | Incidence and time to development of posttransplant diabetes mellitus (PTDM) |
| Immunosuppressants | from time of transplantation up to 10 years | Type of IS, Changes of IS |
| Bone disease | from time of transplantation up to 10 years | number of fractures, measured height (meters) |
| Quality of life measures | from time of transplantation up to 10 years | Quality of life by questionnaire (SF36, MTSODS) |
| Pneumocystis jiroveci pneumonia infection | from time of transplantation up to 10 years | Incidence |
| Stroke | from time of transplantation up to 10 years | number and type of events |
| Coronary revascularization procedure | from time of transplantation up to 10 years | number and type of events |
| Carotid surgery | from time of transplantation up to 10 years | number and type of events |
| Revascularisation procedures for symptomatic peripheral artery disease | from time of transplantation up to 10 years | number and type of events |
| Symptomatic peripheral artery disease | from time of transplantation up to 10 years | number and type of Events, classification by Fontaine |
| cardiac death | from time of transplantation to the date of the event for up to 10 years, whichever comes first | number and type of events |
Contacts
Primary ContactLukas J Lehner, MD
Backup ContactKlemens Budde, MD
Outcome results
None listed