Efficacy and Safety of a Quadruple Regimen in Patients with Gastrointestinal Complications after Renal Transplantation

Abstract

Objectives: The aim of this study was to evaluate the efficacy and safety of a quadruple regimen including standard-dose tacrolimus, low-dose enteric-coated mycophenolate sodium (EC-MPS), low-dose mizoribine (MZR), and corticosteroids compared with regimens containing standard-dose tacrolimus, corticosteroids plus either low-dose EC-MPS or standard-dose MZR in patients with mycophenolic acid (MPA)-related GI complications after kidney transplantation. Methods: Between August 2016 and October 2018 in Qilu Hospital of Shandong University, 115 living donor kidney transplantations with MPA-related GI complications were enrolled in a single-center, prospective study. Thirty-six recipients were assigned to the low-dose EC-MPS plus low-dose MZR group. Thirty-seven recipients were assigned to the low-dose EC-MPS group, and thirty-nine recipients were assigned to the standard-dose MZR group. The three groups were compared with the Gastrointestinal Symptom Rating Scale (GSRS), graft rejection, human leukocyte antigen (HLA) antibody, serum creatinine levels, estimated glomerular filtration rate (eGFR), and incidence of adverse effects. Results: A significant improvement in GI symptoms was observed in all three groups compared with baseline. Renal function was better in the low-dose EC-MPS plus low-dose MZR group. The incidence of graft rejection and cytomegalovirus (CMV) and polyomavirus BK (BKV) infection with the incidence of hyperuricemia were all significantly lower in the low-dose EC-MPS plus low-dose MZR group. Conclusions: The quadruple regimen may be not only equivalent to regimens containing standard-dose tacrolimus, corticosteroids plus either low-dose EC-MPS or standard-dose MZR in improving GI symptoms after kidney transplantation but also advantageous for renal function, graft rejection rates, and the incidence of adverse effects. Funding: This study was funded by the Provincial Key Technologies R & D Program of Shandong Province (Grant No. 26010104011025), National Natural Science Foundation of China (Grant No. 81600092), Key Research and Development Plan of Shandong Province (Grant No. 2017GSF218003). Declaration of Interest: The authors declare no competing interests. Ethical Approval: Patients gave their informed consent to be in the study, and the study protocol was approved by the ethics committee of Qilu Hospital of Shandong University, China (2016Qilu Hospital of Shandong University IRB Approval No. 2016041).