AUTHOR=Zeng Jun , Zhong Qiang , Feng Xiaobing , Li Linde , Feng Shijian , Fan Yu , Song Turun , Huang Zhongli , Wang Xianding , Lin Tao 

TITLE=Conversion From Calcineurin Inhibitors to Mammalian Target of Rapamycin Inhibitors in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.663602

DOI=10.3389/fimmu.2021.663602

ISSN=1664-3224

ABSTRACT=Background
A systematic review and meta-analysis were performed to investigate the efficacy and safety of conversion from CNI to the mammalian-target-of-rapamycin inhibitor (mTORi) in kidney transplant recipients (KTRs).
Methods
MEDLINE, EMBASE, PubMed, and Cochrane Library were searched to identify randomized controlled trials (RCTs) that compared continuation of CNI with conversion to mTORi therapy. 
Results
Twenty-nine RCTs (5,747 KTRs) were included in our analysis. Meta-analysis of glomerular filtration rate (SMD 0.20; 95%CI 0.10-0.31; P<0.01), and malignancy (RR 0.74; 95%CI 0.55-0.99; P=0.04) demonstrated a significant advantage of mTORi conversion over CNI continuation. However, the risk of rejection (RR 1.58; 95%CI 1.22-2.04; P<0.01), infection (RR 1.55; 95%CI 1.01-1.31; P=0.04), proteinuria (RR 1.87; 95%CI 1.34-2.59; P<0.01), leukopenia (RR 1.56; 95%CI 1.27-1.91; P<0.01), acne (RR 6.43; 95%CI 3.43-12.04; P<0.01), and mouth ulcer (RR 11.70; 95%CI 6.18-22.17; P<0.01) were higher in mTORi trials. More patients in the conversion group had to discontinue study medication (RR 2.52; 95%CI 1.75-3.63; P<0.01). There was no significant difference between the two groups with regard to death, graft loss, diabetes, chronic allograft nephropathy, and interstitial fibrosis / tubular atrophy.
Conculsions
Posttransplant patients have a better graft function and lower incidence of malignancy after conversion from CNI to mTORi therapy. However, this conversion strategy may be prevented by the higher drug discontinuation rate due to mTORi-associated adverse events, such as more rejection, infection, proteinuria, leukopenia, acne and mouth ulcer, indicating that conversion therapy may only be a treatment option in selected patients.