Abstract
BackgroundA systematic review and meta-analysis were performed to investigate the efficacy and safety of conversion from calcineurin inhibitors (CNIs) to mammalian target of rapamycin inhibitors (mTORi) in kidney transplant recipients (KTRs).MethodsMEDLINE, EMBASE, PubMed, and Cochrane Library were searched to identify randomized controlled trials (RCTs) that compared the continuation of CNI with conversion to mTORi therapy.ResultsTwenty-nine RCTs (5,747 KTRs) were included in our analysis. Meta-analysis of the 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 acute 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 the mTORi group. 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.ConclusionsPosttransplant 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 acute rejection, infection, proteinuria, leukopenia, acne, and mouth ulcer, indicating that conversion therapy may only be a treatment option in selected patients.
Highlights
Most kidney transplant recipients (KTRs) currently receive calcineurin inhibitor (CNI) therapy, which has remarkably reduced acute rejection (AR) episodes and improved early graft survival [1]
Studies were eligible if they met the following criteria: (a) randomized controlled trial (RCT) of conversion from CNIs to Mammalian target of rapamycin inhibitors (mTORi) maintenance immunosuppressive regimen; (b) participants were the recipients of a single organ kidney transplant from a living or deceased donor; (c) initial immunosuppression consisted of a CNI but not an mTORi; and (d) KTRs were randomly assigned to either continue with current CNI therapy or be converted from the CNI to mTORi
Among these 29 trials, 22 trials reported the time of conversion to mTORi within 6 months after transplantation; the rest were more than 6 months
Summary
Most kidney transplant recipients (KTRs) currently receive calcineurin inhibitor (CNI) therapy, which has remarkably reduced acute rejection (AR) episodes and improved early graft survival [1]. The CNI can promote cardiovascular events and malignancies, which are the leading causes of premature death with a functioning graft [4, 5]. This discrepancy has prompted investigations into CNI retention strategies, which maintain adequate immunosuppressive effects without compromising safety [6]. A systematic review and meta-analysis were performed to investigate the efficacy and safety of conversion from calcineurin inhibitors (CNIs) to mammalian target of rapamycin inhibitors (mTORi) in kidney transplant recipients (KTRs)
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