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Induction therapy with antilymphocyte biological agents is widely used after kidney transplantation, most commonly T lymphocyte‐depleting rabbit‐derived antithymocyte globulin (rATG) or an IL‐2 receptor antagonist (IL2RA). Early randomized trials showed that rATGor IL2RAinduction reduces early acute rejection, prompting recommendations by Kidney Disease Improving Global Outcomes that IL2RAinduction be used routinely in first‐line therapy after kidney transplantation, with lymphocyte‐depleting induction reserved for high‐risk cases. These studies, however, mainly used outdated maintenance regimens. No large randomized trial has examined the effect of IL2RAor rATGinduction versus no induction in patients receiving tacrolimus, mycophenolic acid and steroids. With this triple maintenance therapy, the addition of induction may achieve an absolute risk reduction for acute rejection of only 1–4% in standard‐risk patients without improving graft or patient survival. In contrast, rATGinduction lowers the relative risk of acute rejection by almost 50% versus IL2RAin patients with high immunological risk. These recent data raise questions about the need for IL2RAin kidney transplantation, as it may no longer be beneficial in standard‐risk transplantation and may be inferior to rATGin high‐risk situations. Updated evidence‐based guidelines are necessary to support clinicians deciding whether and what induction therapy is required for their transplant patients today. The authors discuss the role of induction therapy in contemporary kidney transplantation and question the need for interleukin‐2 receptor monoclonal antibodies.

Induction therapy with antilymphocyte biological agents is widely used after kidney transplantation, most commonly T lymphocyte-depleting rabbit-derived antithymocyte globulin (rATG) or an IL-2 receptor antagonist (IL2RA). Early randomized trials showed that rATG or IL2RA induction reduces early acute rejection, prompting recommendations by Kidney Disease Improving Global Outcomes that IL2RA induction be used routinely in first-line therapy after kidney transplantation, with lymphocyte-depleting induction reserved for high-risk cases. These studies, however, mainly used outdated maintenance regimens. No large randomized trial has examined the effect of IL2RA or rATG induction versus no induction in patients receiving tacrolimus, mycophenolic acid and steroids. With this triple maintenance therapy, the addition of induction may achieve an absolute risk reduction for acute rejection of only 1–4% in standard-risk patients without improving graft or patient survival. In contrast, rATG induction lowers the relative risk of acute rejection by almost 50% versus IL2RA in patients with high immunological risk. These recent data raise questions about the need for IL2RA in kidney transplantation, as it may no longer be beneficial in standard-risk transplantation and may be inferior to rATG in high-risk situations. Updated evidence-based guidelines are necessary to support clinicians deciding whether and what induction therapy is required for their transplant patients today.

We previously reported a randomized controlled trial in which 227 de novodeceased‐donor kidney transplant recipients were randomized to rabbit antithymocyte (rATG, Thymoglobulin) or daclizumab if they were considered to be at high immunological risk, defined as high panel reactive antibodies (PRA), loss of a first kidney graft through rejection within 2 years of transplantation, or third or fourth transplantation. Patients treated with rATG had lower incidences of biopsy‐proven acute rejection (BPAR) and steroid‐resistant rejection at 1 year. Patients were followed to 5 years posttransplant in an observational study; findings are described here. Treatment with rATG was associated with a lower rate of BPAR at 5 years (14.2% vs. 26.0% with daclizumab; p = 0.035). Only one rATG‐treated patient (0.9%) and one daclizumab‐treated patient (1.0%) developed BPAR after 1 year. Five‐year graft and patient survival rates, and renal function, were similar between the two groups. Overall graft survival at 5 years was significantly higher in patients without BPAR (81.0% vs. 54.8%; p < 0.001). In conclusion, rATG is superior to daclizumab for the prevention of BPAR among high‐immunological‐risk renal transplant recipients. Overall graft survival at 5 years was approximately 70% with either induction therapy, which compares favorably to low‐risk cohorts. In a follow‐up study from a randomized trial in which 227 de novodeceased‐donor kidney transplant recipients at high immunological risk received rabbit antithymocyte globulin or daclizumab, results at 5 years posttransplant show a lower rate of biopsy‐proven acute rejection for antithymocyte globulin with similar renal function and graft and patient survival rates.

We previously reported a randomized controlled trial in which 227 de novodeceased-donor kidney transplant recipients were randomized to rabbit antithymocyte (rATG, Thymoglobulin) or daclizumab if they were considered to be at high immunological risk, defined as high panel reactive antibodies (PRA), loss of a first kidney graft through rejection within 2 years of transplantation, or third or fourth transplantation. Patients treated with rATG had lower incidences of biopsy-proven acute rejection (BPAR) and steroid-resistant rejection at 1 year. Patients were followed to 5 years posttransplant in an observational study; findings are described here. Treatment with rATG was associated with a lower rate of BPAR at 5 years (14.2% vs. 26.0% with daclizumab; p = 0.035). Only one rATG-treated patient (0.9%) and one daclizumab-treated patient (1.0%) developed BPAR after 1 year. Five-year graft and patient survival rates, and renal function, were similar between the two groups. Overall graft survival at 5 years was significantly higher in patients without BPAR (81.0% vs. 54.8%; p < 0.001). In conclusion, rATG is superior to daclizumab for the prevention of BPAR among high-immunological-risk renal transplant recipients. Overall graft survival at 5 years was approximately 70% with either induction therapy, which compares favorably to low-risk cohorts.