Anti-thymocyte Globulin (ATG) vs. Interleukin-2 Receptor Antagonist (IL-2 RA) in Low Immunologic-Risk Kidney Transplant Recipients

Background: KDIGO recommends IL2-RA as first line induction therapy and a lymphocyte-depleting agent for kidney transplant recipients (KTR) at high immunologic risk. Although, depleting agents reduce acute rejection they also increase the risk of infections and malignancies. However, the evidence is controversial. Methods: Patients were allocated to receive IL2-RA or rATG as induction in a 1:1 ratio. Inclusion criteria: ≥18 years old, LIR – KTR. LIR was defined as PRA <30%,1st kidney transplant from living donor with ABO compatibility. PBL subsets, C3 and IgG determinations were obtained pre-transplant, 7 days and 3 months after. CMV and BK viral loads obtained as per protocol and allograft biopsies performed at 3 and 12 months. All received maintenance with Mycophenolic Acid, Tacrolimus and prednisone. Prophylaxis with Trimethoprim – Sulfamethoxazole was given to all and Valganciclovir to those with moderate-high risk for CMV. Primary outcome: measure the effect of rATG compared to IL2-RA as induction for LIR-KTR in PBL subsets, C3 an IgG levels at 7 days and 3 months after transplant. Secondary outcomes: evaluate the incidence of BPAR and infections. Results: 24 patients were analyzed, 14 received IL2-RA. There was a significant decrease in PBL subsets at 7 days post-transplant in the rATG group. CD4 418 cel/µl (285 – 788 cel/µl) vs 30 cel/µl (2 – 58 cel/µl) p = 0.0002, CD8 58 cel/µl (3 – 108 cel/µl) vs 291 cel/µl (116 – 483 cel/µl) p=0.011; CD4/CD8 ratio 1.8 (1.48 – 2.82) vs 0.76 (0.36 – 0.76) p=0.0002, and NK cells 85 cel/µl (74 – 113.5 cel/µl) vs 34 cel/µl (8 – 65 cel/µl p=0.045). This difference was sustained by month 3 in the CD4 count (935 ± 440 cel/µl vs 228 ± 136 cel /µl, p= 0.002) and CD4/CD8 ratio (0.96 ± 0.65 cel/µl vs 1.79 ± 0.33 cel/µl, p = 0.008); with no difference in CD8, NK cells, C3 and IgG at this point. The IL2-RA group showed significant decrease in CD4 and NK cells by day 7; sustained until month 3 for CD4. During follow up, 1 patient in the IL2-RA group presented an ITU and 1 in the rATG early CMV infection. There was 1 BPAR in IL2-RA vs none in the rATG. Conclusion: rATG is associated with prolonged CD4 suppression but no CD8, what probably lessens the adverse effects, while improving allograft survival.