Dataset Information

Impact of intrapatient variability (IPV) in tacrolimus trough levels on long-term renal transplant function: multicentre collaborative retrospective cohort study protocol.

ABSTRACT:

Introduction

High intrapatient variability (IPV) in tacrolimus trough levels has been shown to be associated with higher rates of renal transplant failure. There is no consensus on what level of IPV constitutes a risk of graft loss. The establishment of such a threshold could help to guide clinicians in identifying at-risk patients to receive targeted interventions to improve IPV and thus outcomes.

Methods and analysis

A multicentre Transplant Audit Collaborative has been established to conduct a retrospective study examining tacrolimus IPV and renal transplant outcomes. Patients in receipt of a renal transplant at participating centres between 2009 and 2014 and fulfilling the inclusion criteria will be included in the study. The aim is to recruit a minimum of 1600 patients with follow-up spanning at least 2 years in order to determine a threshold IPV above which a renal transplant recipient would be considered at increased risk of graft loss. The study also aims to determine any national or regional trends in IPV and any demographic associations.

Ethics and dissemination

Consent will not be sought from patients whose data are used in this study as no additional procedures or information will be required from participants beyond that which would normally take place as part of clinical care. The study will be registered locally in each participating centre in line with local research and development protocols. It is anticipated that the results of this audit will be disseminated locally, in participating NHS Trusts, through national and international meetings and publications in peer-reviewed journals.

SUBMITTER: Goldsmith PM

PROVIDER: S-EPMC5642769 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Publications

Impact of intrapatient variability (IPV) in tacrolimus trough levels on long-term renal transplant function: multicentre collaborative retrospective cohort study protocol.

Goldsmith Petra M PM Bottomley Matthew J MJ Okechukwu Okidi O Ross Victoria C VC Ghita Ryan R Wandless David D Falconer Stuart J SJ Papachristos Stavros S Nash Philip P Androshchuk Vitaliy V Clancy Marc M

BMJ open 20170728 7

<h4>Introduction</h4>High intrapatient variability (IPV) in tacrolimus trough levels has been shown to be associated with higher rates of renal transplant failure. There is no consensus on what level of IPV constitutes a risk of graft loss. The establishment of such a threshold could help to guide clinicians in identifying at-risk patients to receive targeted interventions to improve IPV and thus outcomes.<h4>Methods and analysis</h4>A multicentre Transplant Audit Collaborative has been establis ...[more]

PMID: 28756385

Similar Datasets

Project description:BackgroundKidney transplant recipients with high intrapatient variability (IPV) in tacrolimus (Tac) exposure experience more rejection and reduced graft survival. To understand the underlying pathophysiology of this association, the authors investigated whether patients with high tacrolimus IPV have a more activated immune system than patients with low IPV. In addition, exposure to tacrolimus and mycophenolic acid (MPA) was studied in relation to rejection and graft survival.MethodsAt the time of patient inclusion (5-7 years post-transplantation), the frequency of donor-reactive cells was determined by enzyme-linked immunosorbent assay, and the development of donor-specific anti-Human Leukocyte Antigen antibodies (DSA) was measured by Luminex Single Antigen assay. Tacrolimus IPV was retrospectively calculated between 6 and 12 months and the exposure to tacrolimus and MPA was determined between 1 and 5 years post-transplantation.ResultsA total of 371 kidney transplant recipients were included in this study, of whom 56 developed a rejection episode after 12 months and 60 experienced graft failure after 5-7 years. No correlations were found between tacrolimus IPV or immunosuppression exposure and the number of donor-reactive cells after 5 years of transplantation. DSA were detected more often in patients with low exposure to both tacrolimus and MMF [4/21 (19%) versus 17/350 (4.9%), P = 0.04]. In this cohort, neither tacrolimus IPV nor low overall immunosuppression exposure was associated with a higher incidence of rejection. However, regression analysis showed that a higher tacrolimus IPV was associated with an increased incidence of graft failure (odds ratio = 1.03, P = 0.02).ConclusionsThis study verifies the relationship between high tacrolimus IPV and impaired kidney allograft survival in long-term follow-up. DSA was also found to be more prevalent in patients with subtherapeutic concentrations of tacrolimus and MPA. An increased prevalence of donor-specific alloreactivity is yet to be demonstrated in patients with high IPV.

Dataset Information

Impact of intrapatient variability (IPV) in tacrolimus trough levels on long-term renal transplant function: multicentre collaborative retrospective cohort study protocol.

Introduction

Methods and analysis

Ethics and dissemination

Publications

Impact of intrapatient variability (IPV) in tacrolimus trough levels on long-term renal transplant function: multicentre collaborative retrospective cohort study protocol.

Similar Datasets

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