Lingfei Zhao1,2, Chenxia Hu3, Fei Han1, Dajin Chen1, Jun Cheng1, Jianyong Wu1, Wenhan Peng1, Jianghua Chen4. 1. Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China. 2. Institute of Nephrology, Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China. 3. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China. 4. Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China. zjukidney@zju.edu.cn.
Abstract
OBJECTIVE: The 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. METHODS: PubMed, Embase, EBSCO, Ovid, and the Cochrane Library were searched for prospective clinical trials that compared MSCs with traditional regimens for induction therapy in KT. RESULTS: Four 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. CONCLUSION: Induction 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.
OBJECTIVE: The 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. METHODS: PubMed, Embase, EBSCO, Ovid, and the Cochrane Library were searched for prospective clinical trials that compared MSCs with traditional regimens for induction therapy in KT. RESULTS: Four 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. CONCLUSION: Induction 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.
Authors: Samuel Chan; Carmel M Hawley; Katrina L Campbell; Mark Morrison; Scott B Campbell; Nicole M Isbel; Ross S Francis; Elliot G Playford; David W Johnson Journal: Nephrology (Carlton) Date: 2019-10-15 Impact factor: 2.506