Clinical trial NCT03978065: The Renal Transplant Outcome Prediction and Validation Study
Official title: The Renal Transplant Outcome Prediction and Validation Study (TOPVAS)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Ischemia Reperfusion Injury
Lead sponsor: Medical University Innsbruck
Sponsor class: OTHER
First posted: 2019-06-06
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective, single-center pilot study
Primary purpose: DIAGNOSTIC

Brief summary: The number of patients with end stage renal disease is increasing continuously and kidney transplantation is the preferred treatment modality. Modern immunosuppressive therapy has reduced the number of acute rejection episodes and increased one year allograft survival dramatically. Nonetheless, 4% of allografts are lost beyond the first year annually due to a multifactorial process and the latter number has not changed for decades. One of the most important factors to determine long-term success after kidney transplantation is the quality of the donor organ. For example, transplantation of organs from elderly or extended criteria donors results in reduced allograft and patient survival.

In previous work, the investigators specifically focused on age-associated molecular signatures including telomere length and mRNA expression levels of the cell cycle inhibitors CDKN2A (p16INK4a) and CDKN1A (p21WAF1) and assessed these parameters in pre-implantation biopsies of 54 patients. In a linear regression analysis CDKN2A turned out to be the best single predictor for serum creatinine after 1 year followed by donor age and telomere length. A multiple linear regression analysis revealed that the combination of CDKN2A values and donor age yielded even higher predictive values. In another study the investigators were able to show an interaction between donor age and use of calcineurin inhibitors with regard to outcome after renal transplantation.

During these past activities an extensive set of whole genome transcriptomics profile information from zero hour biopsies and clinical follow-up data has been collected. In the TOPVAS study, existing data derived from 72 of the above mentioned set of biopsies (exclusion of live donor grafts) will be analysed with state of the art bioinformatical/system biology tools to derive a general (not purely age associated) prognostic biomarker panel for functional transplant outcome two years after transplantation. This marker panel will also be used to define organs preferentially suitable for MMF/tacrolimus based immunosuppression. Both panels will then be validated for their prognostic and predictive information on the long-term outcome after transplantation in a new independent patient population treated with tacrolimus and MMF. In addition to biomarker assessment and in pursue of identifying alternative and/or complementary parameters with predictive value , an advanced morphological investigation of tissue biopsy life stains will be performed employing an innovative cell viability staining technology ("BIOPSYCHRONOLOGY").


Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Recipient age \> 18 years
* First or second deceased donor kidney transplantation
* Panel reactive antibody frequency \<50%

Exclusion Criteria:

* Combined kidney transplantation with another organ
* Living donor kidney transplantation
* TOPVAS is a interventional prospective cohort study and participation of patients in other randomized prospective interventional trials does not per se violate the protocol

Primary outcomes:
measure: The number of dialysis in the first 7 days post transplant
timeFrame: 7 days
measure: Kidney parenchyma quality
timeFrame: before transplant
Secondary outcomes:
Other outcomes:
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