Implication of interleukin-2 receptor antibody induction therapy in standard risk renal transplant in the tacrolimus era: a meta-analysis.
Topic: Immunotherapy

Interleukin-2 (IL-2) antagonist has been used as an induction therapy in many centres in calcineurin inhibitor-sparing regimens. Tacrolimus has overwhelmingly replaced cyclosporine in the maintenance immunosuppressive protocols in many transplant centres. The aim of our study and meta-analysis is to explore the effect of IL-2 induction therapy on the rate of rejection and patient and graft survival in standard-risk renal transplant patients with tacrolimus-based maintenance immunotherapy. Secondary aims included assessment of the effect of IL-2 induction therapy on creatinine change and the risk of cytomegalovirus (CMV) infection.

PICO
Population: Standard-risk renal transplant patients with tacrolimus-based maintenance immunotherapy
Intervention: Interleukin-2 receptor antibody induction therapy
Comparison: No IL-2 induction therapy or alternative induction therapy
Outcomes: Rate of rejection, patient and graft survival, creatinine change, risk of cytomegalovirus (CMV) infection

Included studies:
title: Reduced exposure to calcineurin inhibitors in renal transplantation.
abstract: Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens.
title: Usefulness of Tacrolimus without Basiliximab in Well-Matched Living-Donor Renal Transplant Recipients in Korea.
abstract: Basiliximab is used alongside tacrolimus-based immunosuppression for routine induction therapy, even for well-matched living-donor renal transplant recipients. Because tacrolimus is a different drug from cyclosporine, this study examined the utility of tacrolimus-based immunosuppression without basiliximab for well-matched living-donor renal transplant recipients.
title: Sequential protocols using basiliximab versus antithymocyte globulins in renal-transplant patients receiving mycophenolate mofetil and steroids.
abstract: Sequential anti-thymocyte globulins (ATG)/cyclosporine immunosuppression has two main advantages: delayed introduction of the nephrotoxic drug cyclosporine and prevention of acute rejection. Basiliximab, a recently developed chimeric monoclonal antibody that selectively depletes the minor subpopulation of activated T lymphocytes, has been shown to reduce the incidence of acute rejection when used with cyclosporine introduced on day 1.
title: Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group.
abstract: Monoclonal antibodies that block the high-affinity interleukin-2 receptor expressed on alloantigen-reactive T lymphocytes may cause selective immunosuppression. Daclizumab is a genetically engineered human IgG1 monoclonal antibody that binds specifically to the alpha chain of the interleukin-2 receptor and may thus reduce the risk of rejection after renal transplantation.
title: Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group.
abstract: Currently available immunosuppressive regimens for cadaver-kidney recipients are far from ideal because acute-rejection episodes occur in about 30% to 50% of these patients. In the phase III study described here we assessed the ability of basiliximab, a chimeric interleukin (IL)-2 receptor monoclonal antibody, to prevent acute-rejection episodes in renal allograft recipients.
title: Anti-CD25 monoclonal antibody sequential immunosuppressive induction therapy in renal transplants with high risk of delayed graft function.
abstract: There is little experience on the use of monoclonal antibodies that block the high-affinity interleukin-2 receptor (basiliximab and daclizumab) in sequential therapy in renal transplants with risk of delayed graft function. This study sougth to test the efficacy and safety of the substitution of anticalcineurins with two doses of basiliximab or daclizumab in the immediate posttransplant period for recipients at risk of delayed renal graft function. Immunosuppression consisted of steroids, mycophenolate mofetil, and two doses of basiliximab (20 mg/day) on days 0 and 4 posttransplant or daclizumab (1 mg/kg per day) on days 0 and 15 posttransplant. Anticalcineurins were not administered until the beginning of graft function. Among 49 recipients (mean age 63.5 +/- 10.5 years), 40 received a kidney from a donor over 60 years of age, three from a non-heart-beating donor, and six from donors with an acute elevation of serum creatinine to 2.4 +/- 0.86 (1.7-3.7). At a mean follow-up of 14.2 +/- 8.4 months, five patients experienced acute rejection episodes. Only 15 patients needed posttransplant dialysis (2.7 +/- 1.6). In 11 patients, cyclosporine (CsA) was introduced at 6 +/- 2.9 days posttransplant and in 37, tacrolimus on 8.6 +/- 3.6 days posttransplant. The incidence of kidney graft loss was 16.3%. Patient survival was 96%. Thirty-nine recipients are alive with functioning grafts, with mean serum creatinine of 1.4 mg/dL. In conclusion, substitution for anticalcineurins with interleukin-2-receptor blockade in the immediate posttransplant period for patients at risk of delayed graft function minimizes nephrotoxicity and reduces tubular necrosis, without increasing the risk of an acute rejection episode.
title: Early outcomes of thymoglobulin and basiliximab induction in kidney transplantation: application of statistical approaches to reduce bias in observational comparisons.
abstract: Retrospective comparison of treatment-related kidney transplant outcomes may be facilitated by multivariable statistical adjustments and case-matching.
title: Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and Mycophenolate.
abstract: IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent for induction therapy in renal transplantation. However, this remains controversial in deceased donor renal transplantation (DDRT) maintained on tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids.
title: Tacrolimus, Mycophenolate Mofetil, and Low-Dose Steroids With or Without Interleukin-2 Receptor Antibody Induction Therapy: A Retrospective Cohort Analysis.
abstract: Selective interleukin-2 receptor (IL2R) blockade is one option to decrease acute rejection rates in kidney transplant recipients. However, there are little data on the impact of basiliximab in a triple immunosuppressive regimen (tacrolimus, mycophenolate mofetil, and low-dose steroids). Thus, this analysis aims at investigating the impact of basiliximab induction on rejection rates and immediate graft function following kidney transplantation.
title: The impact of IL2ra induction therapy in kidney transplantation using tacrolimus- and mycophenolate-based immunosuppression.
abstract: IL2 receptor antagonist (IL2ra) induction therapy has gained favor due to an excellent safety profile and improved outcomes in randomized trials using cyclosporine-based immunosuppression. However, there have been no large randomized trials or retrospective analyses examining the effect of IL2ra versus no induction using tacrolimus and mycophenolate (TAC/MPA)-based therapy.
title: Induction Therapies in Live Donor Kidney Transplantation on Tacrolimus and Mycophenolate With or Without Steroid Maintenance.
abstract: Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first line agent in living donor renal transplantation (LRT). However, use of IL2-RA remains controversial in LRT with tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids.
title: A long-term comparison of tacrolimus (FK506) and cyclosporine in kidney transplantation: evidence for improved allograft survival at five years.
abstract: The 1-year results of the Phase III U.S. Multicenter Trial comparing tacrolimus (FK506)- and cyclosporine (CsA)-based immunosuppressive therapy in kidney transplantation revealed a significant reduction in the incidence and severity of acute rejection episodes among patients maintained on tacrolimus. The present report at 5 years of follow-up focuses on the long-term impact of tacrolimus treatment on kidney allograft outcome.