Abstract

ObjectiveThe aim of this meta-analysis was to evaluate the therapeutic effects of mesenchymal stromal cells (MSCs) versus traditional regimens for induction therapy in kidney transplantation (KT), especially the safety of MSC infusion, practicability of MSCs as induction therapy agents, and posttransplant complications.MethodsPubMed, Embase, EBSCO, Ovid, and the Cochrane Library were searched for prospective clinical trials that compared MSCs with traditional regimens for induction therapy in KT.ResultsFour trials were included, including a total of 197 patients. The pooled results revealed that MSC therapy had a lower 1-year infection rate than did the traditional therapies (RR = 0.65, 95% CI: 0.46–0.9, P = 0.01). There were no significant differences between the two protocols regarding the 1-year acute rejection (AR) rate (RR = 0.77, 95% CI: 0.41–1.45, P = 0.42), 1-year graft survival rate (RR = 0.99, 95% CI: 0.95–1.03, P = 0.74), delayed graft function (DGF) rate (RR = 0.54, 95% CI: 0.21–1.38, P = 0.2) and renal graft function at 1 month (MD = −1.56, 95% CI: − 14.2–11.08, p = 0.81), 3 months (MD = 0.15, 95% CI: − 5.63–5.93, p = 0.96), 6 months (MD = − 1.95, 95% CI: − 9.87–5.97, p = 0.63), and 12 months (MD = − 1.13, 95% CI: − 7.16–4.89, p = 0.71) postsurgery. Subgroup analysis demonstrated that the 1-year AR rate, 1-year graft survival rate, DGF rate, and renal graft function at 12 months postsurgery did not significantly differ between the low-dose calcineurin inhibitor (CNI) group and the standard-dose CNI group, indicating the potential benefits of successful CNI sparing in combination with MSC treatment. Moreover, when MSCs were applied as an alternative therapy rather than an additional therapy or allogeneic MSCs were utilized instead of autologous MSCs, all of the outcomes mentioned above were comparable.ConclusionInduction therapy with MSCs is safe and has similar immune response modulation effects to those of traditional regimens in the short term in KT recipients. However, regarding the long-term effects, as suggested by the 1-year infection rate and the potential of CNI sparing, MSC therapy has significant advantages. However, these advantages should be further verified in more well-designed, multicenter randomized controlled trials (RCTs) with large sample sizes and long follow-up periods.

Highlights

  • Kidney transplantation (KT) is still the best treatment choice for end-stage renal disease (ESRD)

  • We mainly focused on the safety and practicability of mesenchymal stromal cells (MSCs) infusion compared with traditional regimens as induction therapy in KT, especially in terms of the infusion reactions, acute rejection (AR) rate, delayed graft function (DGF) rate, and allograft survival

  • One study was a reanalysis of a former study, two studies reported the outcomes of co-fusion MSCs together with other stem cells, and one study did not intend to inject MSCs for induction therapy

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Summary

Introduction

Kidney transplantation (KT) is still the best treatment choice for end-stage renal disease (ESRD). Due to the development of tissue type-matching and immunosuppressive agents, the risk for acute rejection (AR) has been effectively reduced. Posttransplant complications related to current immunosuppressive drugs are new issues that should be resolved. The long-term consumption of regular immunosuppressive drugs, including corticosteroids, calcineurin inhibitors (CNIs), antimetabolites, and sometimes lymphodepletion, can significantly increase the risk of some important adverse effects, such as nephrotoxicity, infection, tumorigenicity, diabetes, and cardiovascular diseases, which can affect the long-term graft outcomes and can even sometimes be life-threatening [1,2,3,4,5]. Despite great efforts in drug innovations, the drawbacks mentioned above have not yet been resolved, and the hazards affecting long-term graft survival have failed to substantially decrease [7]. Novel immunosuppressive strategies that minimize posttransplant complications while maintaining adequate immunosuppression need to be explored

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