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.

An open-label randomized clinical trial to evaluate the efficacy of everolimus versus tacrolimus in triple maintenance immunosuppressive therapy for kidney transplant patients

“…The rATG concentration was reduced to 1 mg/kg when the cell count was <300 cells/mm 3 , and patients with <5×10 4 platelets/mm 3 received 0.5 mg/kg. The rATG treatment was temporarily suspended or interrupted if severe adverse events, such as anaphylaxis, pulmonary edema, malignancies, or virus infections, were detected clinically or through laboratory testing ( 28 ). Patients with antibody-mediated rejection (AMR), who were diagnosed by biopsy and tested positive for complement fraction (C4d+) and donor-specific antibody (DSA+), were treated using a combination of plasmapheresis, 720 mg MMF twice a day, and immunotherapy with rATG from 5 to 7 days, adjusted according to the minimum leukocyte and platelet levels, as described above.…”

“…Drug concentrations were assessed after transplantation for each patient weekly to obtain a target whole-blood level in the first month, every 15 days in the 2nd and 3rd months, monthly for 4 to 12 months, every two months for the second year, every three months for the third year, and each semester in the following years as described in the methodology, and according to previous studies carried out by our research group as published by Lasmar et al ( 28 ).…”

Optimal Immunosuppression Strategy in the Sensitized Kidney Transplant Recipient

“…Rabbit antithymocyte (rATG) polyclonal antibody or interleukin-2 receptor monoclonal antibodies are the most common agents used for induction in non-sensitized patients. Sensitized patients with preformed HLA antibodies are at greater risk of cellular and humoral rejection, and outcomes can be optimized by using polyclonal induction agents, such as ATG or alemtuzumab, that are associated with a lower risk of rejection and better graft survival [22][23][24][25]. However, the impact of different induction approaches on sensitized patients has not been fully elucidated and the variability in induction therapy can be largely attributed to transplant center choice and clinician preference rather than patient or donor characteristics [23][24][25][26].…”

Pretransplant Malnutrition Risk Score: A Simple and Useful Tool for Predicting Kidney Transplant Outcomes

“…This maintenance immunosuppressive protocol was adjusted for patients who had adverse effects of calcineurin inhibitors proved by biopsy, diarrhea and abdominal pain, weight loss, or skin cancer or when virus reinfection by cytomegalovirus, polyomavirus, or human papilloma virus was detected. 27 The graft function was evaluated based on measured using serum creatinine levels.…”