Effects of immunotherapy induction on outcome and graft survival of kidney-transplanted patients with different immunological risk of rejection

Abstract

Background: In kidney transplantation, immunotherapy with thymoglobulin (rATG) has been used to down-regulate the patient immune system. rATG is a powerful immunobiologic drug used to deplete lymphocytes to prevent early acute rejection. The aim of this research was to evaluate the effects of immunotherapy by rATG on graft suvival during a 9-year period in kidney-transplanted patients with different immunological profiles.

Methods: A sample of 469 patients were allocated into four groups (G) based on immunological risk of rejection: G1, low risk, not sensitized recipients, solid-phase immunoassay with single antigen beads (SPI-SAB) < 10%; G2, medium risk I, sensitized recipients, SPI-SAB ≥ 10 < 50%; G3, medium risk II sensitized (SPI-SAB ≥50%); and G4, high risk, sensitized recipients, SPI-SAB- donor-specific antibody positive (DSA+). Only patients from G3 and G4 received immunotherapy.

Results: Of 255 patients who received a kidney from a living donor (LD), 42 (16.47%) from all groups (G) had T-cell-mediated rejection (TCMR) and four (G1) lost their grafts, 8 (3.14%) had antibody-mediated rejection (AMR), and two lost their graft in G1 and G4. Of 214 patients who received a kidney from deceased donors (DD), 37 (17.29%) had TCMR with one lost graft in G1. AMR was shown in 13 (6.07%) patients, with three losses observed in G2. Statistical differences between the groups in the 9-year graft survival rate were found only in the comparison of G1 versus G2 (P = 0.005) and G2 versus G4 (P = 0.047) for DD. For LD, no statistical differences were found.

Conclusion: This clinical retrospective study shows that immunotherapy induction was associated with improvement of outcomes, graft function, and survival in patients treated with immunotherapy in comparison with patients who did not received induction therapy. These findings strongly suggest that immunotherapy should be used for all patients transplanted with kidneys from deceased donors.

Keywords: Graft survival; Immunotherapy induction; Kidney transplantation; Outcome; Risk of rejection; Thymoglobulin.

Fig. 1

Analysis of graft survival by Kaplan-Meier method in groups of patients with different immunological risks of antibody-mediated rejection. a: living donor. b: deceased donor. G1: low risk, not sensitized recipients, solid-phase immunoassay with single antigen beads (SPI-SAB) < 10%; G2: medium risk I, sensitized recipients, SPI-SAB ≥ 10 < 50%; G3: medium risk II sensitized (SPI-SAB ≥50%); G4: high-risk, sensitized recipients, SPI-SAB-DSA+. For patients who received DD, statically significant differences were found only in the comparison between G1 versus G2 (P = 0.005) and G2 versus G4 (P = 0.047)