The influence of the antithymocyte globulin dose on clinical outcomes of patients undergoing kidney retransplantation

Abstract

Optimizing antithymocyte globulin (rATG) dosage is critical for high immunological risk patients undergoing a repeat kidney transplant. This natural retrospective cohort study compared clinical outcomes of two successive cohorts of consecutive recipients of retransplants receiving 5 x 1 mg/kg (rATG-5, n = 100) or a single 3 mg/kg (rATG-3, n = 110) dose of rATG induction therapy. All patients had negative complement-dependent cytotoxicity crossmatch and no anti-HLA A, B, DR donor-specific antibodies (DSA). The primary endpoint was efficacy failure (first biopsy-proven acute rejection, graft loss, or death) at 12 months. There was no difference in the cumulative incidence of efficacy failure (18.0% vs. 21.8%, HR = 1.22, 95% CI 0.66–2.25), respectively. There were no differences in 3-years freedom from biopsy proven acute rejection, and patient, graft, and death-censored graft survivals. There were no differences in the incidence of surgical complications (25.0% vs. 18.2%; p 0.151), early hospital readmission (27.8% vs. 29.5%; p = 0.877) and CMV infections (49% vs. 40%; p = 0.190). There were also no differences in the incidence (59.6% vs. 58.7%, p = 0.897) and duration of delayed graft function but a stable difference in estimate glomerular filtration rate was observed from month 1 (54.7±28.8 vs. 44.1±25.3 ml/min/1.73 m2, p = 0.005) to month 36 (51.1±27.7 vs. 42.5±24.5, p = 0.019). Mean urinary protein concentration (month 36: 0.38±0.81 vs. 0.70±2.40 g/ml, p = 0.008) and mean chronic glomerular Banff score in for cause biopsies (months 4–36: 0.0±0.0 vs. 0.04±0.26, p = 0.044) were higher in the rATG-3 group. This cohort analysis did not detect differences in the incidence of efficacy failure and in safety outcomes at 12 months among recipients of kidney retransplants without A, B, and DR DSA, receiving induction therapy with a single 3 mg/kg rATG dose or the traditional 5 mg/kg rATG.

Evaluating anti-thymocyte globulin induction doses for better allograft and patient survival in Asian kidney transplant recipients

“…A recent study by Mehta et al showed that patients in the regular dose ATG (≥ 5 mg/kg) group had more favorable outcomes in terms of early (within six months posttransplant) rejection compared with the low-dose (< 5 mg/kg) group 26 . On the other hand, another study by Linhares et al reported that the 3 mg/kg and 5 mg/kg ATG induction groups did not show significant differences in the incidence of efficacy failure (first BPAR, graft failure, or mortality) and in safety outcomes at twelve months posttransplant 27 ; however, the study by Linhares et al was limited due to its single-center, retrospective design, small number of patients, short follow-up duration, and the fact that only those who underwent repeat kidney transplantation were included.…”

Rabbit antithymocyte globulin dose and early subclinical and clinical rejections in kidney transplantation

“…In fact, in the initial randomized study by Brennan et al., 9 only 69% of the recipients ended up getting the intended dose. In a more recent study that looked at ATG dosing in retransplant patients, only 64% of the patients received the full 5 mg/kg course of ATG 10 . We therefore wanted to see if there was a difference in the proportion of patients having rejections (clinical or subclinical), if they received less than our planned lower threshold dose of 5 mg/kg.…”

“…In a more recent study that looked at ATG dosing in retransplant patients, only 64% of the patients received the full 5 mg/kg course of ATG. 10 We therefore wanted to see if there was a difference in the proportion of patients having rejections (clinical or subclinical), if they received less than our planned lower threshold dose of 5 mg/kg. Prior studies have utilized a wide range of ATG dosing, between 3 and 10.5 mg/kg.…”