Subclinical rejection and allograft survival in kidney transplantation: protocol for a systematic review and meta-analysis

Abstract

Introduction Subclinical rejection (SCR) refers to the presence of acute rejection without accompanying kidney allograft dysfunction. The impact of SCR on long-term graft survival remains a subject of ongoing debate.Methods and analysis We will perform a systematic search of databases including MEDLINE, Embase and Cochrane Central, from January 1995 to November 2023. We will include English-language studies involving adult kidney transplant patients who investigated SCR. We will exclude studies focused on ‘for-cause’ biopsies. Both title, abstract screening and full-text screening will be performed by two or more reviewers. The primary outcome of this study will be death-censored allograft loss. The secondary outcome will include development of subsequent rejection. For time-dependent outcomes, we will prioritise HRs and the 95% CIs. In cases where HRs are unavailable, we will calculate risk ratios based on the recorded events. The risk of bias will be assessed using the Cochrane Collaboration’s revised tool for assessing the risk of bias in randomised trials and the Newcastle-Ottawa scale for cohort studies. We will employ a random effects model. We will evaluate heterogeneity using the I2 variable. We will assess publication bias by funnel plots, Begg and Mazumdar test, and Egger’s test.Ethics and dissemination Ethics approval does not apply as no original data will be collected. The results will be disseminated through peer-reviewed publications and conference presentations.PROSPERO registration number CRD42023463536.