Safety of Immunosuppressive Drugs Used as Maintenance Therapy in Kidney Transplantation: A Systematic Review and Meta-Analysis

Abstract

To evaluate the safety of regimens containing calcineurin inhibitors (CNI), proliferation signal inhibitors (TOR-I) and antimetabolites, we conducted a meta-analysis of randomized clinical trials (RCTs) and observational studies. A total of 4,960 citations were identified in our electronic search and 14 additional articles were identified through hand searching. Forty-eight articles (11,432 participants) from 42 studies (38 RCTs and four cohorts) met the inclusion criteria. Meta-analysis results revealed the following: (i) tacrolimus was associated with an increased risk for diabetes and lower risk of dyslipidemia, compared to cyclosporine; (ii) mycophenolate mofetil (MMF) was associated with increased risk for total infections, abdominal pain, diarrhea and vomiting, compared with azathioprine; (iii) sirolimus was associated with higher risk of anemia, diabetes, dyslipidemia, lymphoceles and withdrawal compared to tacrolimus or cyclosporine, and cyclosporine was associated with an increased risk of CMV infection; (iv) the combination of CNI with antimetabolites was associated with more adverse events than CNI alone; (v) TOR-I was related to more adverse events than MMF. The data observed in this meta-analysis are similar to those describe by others authors; thus, the choice of treatment must be made by the clinical staff based on specific patient characteristics.

Efficacy and Safety of Everolimus for Maintenance Immunosuppression of Kidney Transplantation: A Meta-Analysis of Randomized Controlled Trials

“…Mammalian target of rapamycin inhibitors are associated with a number of well-described side effects [4, 13, 18] that may limit the ability of patients to tolerate them. Our analysis confirmed this, indicating that the risk of study discontinuation due to AEs after EVR conversion was 2.63 times that of the patients maintained on CNIs.…”

“…Meanwhile, tacrolimus has been recommended as a first-line agent for kidney transplantation recipients in kidney disease improving global outcomes (KDIGO) in 2009 [3]. However, CNIs are associated with a number of potentially serious side effects, including nephrotoxicity, diabetes, hypertension, and neurotoxicity that contribute to morbidity and mortality after transplantation [4–8]. Upon the fifth year, 90% of grafts revealed evidence of CNI-related lesions, and whereas early acute nephrotoxicity is typically reversible with CNI minimization; chronic lesions cannot be altered once initiated [5].…”

Symptom Experience Associated With Immunosuppressive Medications in Chinese Kidney Transplant Recipients

“…In our findings, high blood sugar caused high distress in the 4‐ to 16‐year cohort, in which the ratio of the cyclosporine‐based regimen utilization was higher. High blood sugar is a common symptom related to calcineurin inhibitors (Almeida et al., ). However, the occurrence of high blood sugar was low in these study participants.…”

“…Multiple classes of medications have been simultaneously used. Usually, the immunosuppressive regimens include calcineurin inhibitors such as cyclosporine or tacrolimus; steroids; and antimetabolites such as azathioprine or mycophenolate mofetil or proliferation signal inhibitors such as sirolimus and everolimus worldwide (Almeida et al., ), as well as in China. Moreover, an increasing range of adverse events must be considered when deciding on the optimal immunosuppressive strategy for an individual patient; thus, the balance of advantages and disadvantages is used to determine the regimen of choice.…”

An appraisal of meta‐analysis guidelines: how do they relate to safety outcomes?

“…While serious infections are reported for cyclosporine use in published studies on kidney transplant patients, serious infections are not reported in published studies for psoriasis. Possible reasons for this omission could be changes in data collection over time or different doses used for different indications (i.e., 2.48 ± 0.65 and 4.10 ± 1.58 mg/kg/day for psoriasis versus stable renal transplant) (Almeida et al, 2013;Ito et al, 2014;FDA Safety Information Neoral;FDA Prescribing Information, Neoral).…”