Year: 2016
Type: letter
Abstract: To the Editor: We read with interest the minireview by Hellemans et al, who questioned the continued utility of IL-2 receptor antagonists (IL2RAs) (1Hellemans R Bosmans JL Abramowicz D et al.Induction therapy for kidney transplant recipients: Do we still need anti-IL2 receptor monoclonal antibodies?.Am J Transplant. 2016; (doi:10.1111/ajt/13884[Epub ahead of print])Google Scholar). We thank the authors for addressing an important topic that lacks the rigor of scientific evidence received by maintenance immunosuppressive regimens. 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 (2Ahsan N Holman MJ Jarowenko MV Razzaque MS Yang HC Limited dose monocolonal IL-2R antibody induction protocol after primary kidney transplantation.Am J Transplant. 2002; 2: 568-573Crossref PubMed Scopus (47) Google Scholar). Overall, we feel that the declarative statements made by the authors are not fully supported by the level of evidence that was cited. Furthermore, there appears to be a discrepancy in the authors’ reporting of outcomes based on the type of induction being assessed. In comparing IL2RA and no induction, rejection rates are dismissed, with a focus on the lack of differences in patient or graft survival. In contrast, in comparing IL2RA and rabbit-derived anti–thymocyte globulin (RATG), the lack of long-term differences in patient or graft survival was minimized, and acute rejection was instead the focus (1Hellemans R Bosmans JL Abramowicz D et al.Induction therapy for kidney transplant recipients: Do we still need anti-IL2 receptor monoclonal antibodies?.Am J Transplant. 2016; (doi:10.1111/ajt/13884[Epub ahead of print])Google Scholar). In terms of induction in high-risk kidney transplant recipients, this review failed to include the results of our large prospective randomized trial of induction along with contemporary maintenance immunosuppression and histocompatibility techniques (3Pilch NA Taber DJ Moussa O et al.Prospective randomized controlled trial of rabbit antithymocyte globulin compared with IL-2 receptor antagonist induction therapy in kidney transplantation.Ann Surg. 2014; 259: 888-893Crossref PubMed Scopus (34) Google Scholar). In short, it included a kidney transplant population with diverse immunologic risk factors. Approximately 50% of the participants were black, and >40% had calculated panel reactive antibodies (cPRA) >20%. In total, 200 participants were randomized in a risk-stratified fashion to induction with IL2RA or RATG. The 1-year rates of rejection, death and graft loss were all similar between populations. More biopsy-proven BK virus–associated nephropathy (BKVAN) was present in the RATG cohort, which was predominantly due to the infection rates amongst the white subjects in that cohort. Importantly, a priori subanalyses demonstrated that rejection rates had no correlation with cPRA but were numerically higher in black recipients. This study demonstrated similar efficacy between induction therapies in a pragmatic transplant population and confirmed a risk of more infections, notably BKVAN, with RATG. Although we do not infer that this study should designate a global change in induction therapy, we believe it is worthy of mention in any minireview on the topic. In addition, the lack of short- or long-term adverse effects with IL2RA must be considered when weighing the risks and benefits of induction therapy. Finally, it should be noted that, based on the most recent Scientific Registry of Transplant Recipients report (2014), IL2RA induction therapy is still used in more than one-third of kidney transplant recipients in the United States and thus is thought by transplant clinicians to maintain an important role (4Hart A Smith JM Skeans A et al.OPTN/SRTR 2014 Annual Data Report: Kidney.Am J Transplant. 2016; 16: 11-46Crossref PubMed Scopus (130) Google Scholar). In closing, we appreciate this review but feel that, given the current level of evidence, the authors’ conclusion that there is no place for IL2RA induction therapy is overstated. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.
DOI: 10.1111/ajt.13930
Language: English
Subfield: Transplantation
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,300
OpenAlex ID: W2469097963