Limited Dose Monoclonal IL‐2R Antibody Induction Protocol after Primary Kidney Transplantation

Abstract

This study prospectively compared immunoprophylaxis with a single intraoperative dose (2 mg/kg) of monoclonal interleukin-2 receptor (IL-2R) antibody vs. noninduction in kidney transplant recipients treated with tacrolimus (FK 506), mycophenolate mofetil (MMF) and a prednisone-based immunosuppression regimen. One hundred recipients of first-kidney transplant were enrolled into the study to receive either anti-IL-2R monoclonal antibody, daclizumab (2 mg/kg intraoperatively, limited anti-IL-2R) or no induction (control). Each patient also received oral tacrolimus (dosed to target trough level 10-15 ng/mL), MMF (500 mg bid) and prednisone. The primary efficacy end-point was the incidence of biopsy proven acute rejection during the first 6 months post-transplant. The patients were also followed for 12-month graft function, and graft and patient survival rates. Other than the donor's age being significantly lower in the control group, both groups were comparable with respect to age, weight, gender, race, human leukocyte antigen (HLA)-DR mismatch, panel reactive antibody (%PRA), cold ischemic time, cytomegalovirus (CMV) status, causes of renal failure, and duration and modes of renal replacement therapy (RRT). During the first 6 months, episodes of first biopsy confirmed acute rejection was 3/50 (6%) in the limited anti-IL-2R group and 8/50 (16%) in the controls (p ∞ 0.05). Twelve-month patient 100/98 (%) and graft survival 100/96 (%) were not statistically different. The group receiving limited anti-IL-2R did not have any adverse reactions. Our study demonstrates that a limited (single) 2 mg/kg immunoprophylaxis dose with monoclonal IL-2R antibody (daclizumab) when combined with tacrolimus/ MMF/steroid allows significant reduction in early renal allograft rejection to the single digit level. The therapy with anti-IL-2R antibody is simple and is well tolerated.

Yes, We Still Need IL-2 Receptor Antagonists

“…We agree that the authors based their opinion on well-performed studies with historical maintenance immunosuppression and on large registry studies, which have many inherent weaknesses that prevent definitive conclusions. We also agree with the paucity of evidence regarding benefit for recipients with low immunologic risk over no induction; however, we would like to point out that Ahsan et al demonstrated fewer rejection episodes with IL2RA induction versus none in a randomized trial of low-risk kidney transplant recipients who received contemporary maintenance immunosuppression (2). Overall, we feel that the declarative statements made by the authors are not fully supported by the level of evidence that was cited.…”

Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and Mycophenolate

“…Moreover, a subgroup analysis did not show difference in outcomes when cyclosporin and TAC maintenance regimens were compared. However, other prospective studies reported much lower rates of biopsy-proven rejection at 1 year (8%-15%) among kidney transplant recipients receiving IL2-RA induction and TAC/MPA/steroid maintenance (8,19,20). A recently published RCT with a 5-year follow-up (n=227) compared r-ATG with IL2-RA induction in high-risk DDRT recipients (mostly 75%-85% in each arm; maintained on TAC/MPA/steroid) (21).…”

“…In the era of TAC/MPA maintenance regimens with or without steroids, controversy exists with respect to the added benefit of IL2-RA induction therapy on outcomes of renal transplantation. In fact, there are recent data that support that no induction therapy could achieve acceptable acute rejection rates (#20% at 1 year after transplantation), with similar allograft and patient survival compared with IL2-RA induction in the setting of the TAC/MPA maintenance regimen (8)(9)(10)(11)(12).…”

Induction Therapies in Live Donor Kidney Transplantation on Tacrolimus and Mycophenolate With or Without Steroid Maintenance

“…Prospective randomized multicenter studies and retrospective registry analysis demonstrate that no-induction therapy can achieve acceptable acute rejection rates (10%-20% at 1 year after transplant), with allograft and patient survival similar to other induction modalities in living donor renal transplantation (LRT) (7)(8)(9)(10). However, the current Kidney Disease Improving Global Outcomes (KDIGO) Transplant Work Group guidelines recommend IL2-RA as a first-line induction agent in all types of donor-recipient profiles to reduce risk of acute rejection and allograft loss.…”