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Meta-Analysis
. 2022 Mar;22(3):772-785.
doi: 10.1111/ajt.16907. Epub 2021 Dec 10.

Effectiveness of T cell-mediated rejection therapy: A systematic review and meta-analysis

Julie Ho  1 , George N Okoli  2 , Rasheda Rabbani  2   3 , Otto L T Lam  2 , Viraj K Reddy  2 , Nicole Askin  4 , Christie Rampersad  1 , Aaron Trachtenberg  1 , Chris Wiebe  1 , Peter Nickerson  1 , Ahmed M Abou-Setta  2   3
Affiliations
Meta-Analysis

Effectiveness of T cell-mediated rejection therapy: A systematic review and meta-analysis

Julie Ho et al. Am J Transplant. 2022 Mar.

Abstract

The effectiveness of T cell-mediated rejection (TCMR) therapy for achieving histological remission remains undefined in patients on modern immunosuppression. We systematically identified, critically appraised, and summarized the incidence and histological outcomes after TCMR treatment in patients on tacrolimus (Tac) and mycophenolic acid (MPA). English-language publications were searched in MEDLINE (Ovid), Embase (Ovid), Cochrane Central (Ovid), CINAHL (EBSCO), and Clinicaltrials.gov (NLM) up to January 2021. Study quality was assessed with the National Institutes of Health Study Quality Tool. We pooled results using an inverse variance, random-effects model and report the binomial proportions with associated 95% confidence intervals (95% CI). Statistical heterogeneity was explored using the I2 statistic. From 2875 screened citations, we included 12 studies (1255 participants). Fifty-eight percent were good/high quality while the rest were moderate quality. Thirty-nine percent of patients (95% CI 0.26-0.53, I2 77%) had persistent ≥Banff Borderline TCMR 2-9 months after anti-rejection therapy. Pulse steroids and augmented maintenance immunosuppression were mainstays of therapy, but considerable practice heterogeneity was present. A high proportion of biopsy-proven rejection exists after treatment emphasizing the importance of histology to characterize remission. Anti-rejection therapy is foundational to transplant management but well-designed clinical trials in patients on Tac/MPA immunosuppression are lacking to define the optimal therapeutic approach.

Keywords: clinical research/practice; graft survival; immunosuppression/immune modulation; immunosuppressive regimens; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; rejection: T cell mediated (TCMR); rejection: antibody-mediated (ABMR).

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Figures

FIGURE 1
FIGURE 1
Modified PRISMA flow chart
FIGURE 2
FIGURE 2
Forest plot for persistent ≥Banff Borderline rejection following treatment of ≥Banff Borderline rejection
FIGURE 3
FIGURE 3
Forest plot for persistent ≥Banff Borderline rejection following treatment of ≥Banff 1A rejection
FIGURE 4
FIGURE 4
(A) Forest plot for persistent ≥Banff Borderline rejection following treatment of subclinical ≥Banff Borderline rejection. (B) Forest plot for persistent ≥Banff Borderline rejection following treatment of clinical ≥Banff Borderline rejection
FIGURE 5
FIGURE 5
Forest plot for persistent ≥Banff Borderline rejection following untreated ≥Banff Borderline rejection
FIGURE 6
FIGURE 6
Forest plot for ABMR following treatment of ≥Banff Borderline rejection
FIGURE 7
FIGURE 7
Overview
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