A prospective, randomized, non-blinded, non-inferiority pilot study to assess the effect of low-dose anti-thymocyte globulin with low-dose tacrolimus and early steroid withdrawal on clinical outcomes in non-sensitized living-donor kidney recipients

PLoS One. 2023 Mar 1;18(3):e0280924. doi: 10.1371/journal.pone.0280924. eCollection 2023.

Abstract

Background: The optimal dose of anti-thymocyte globulin (ATG) as an induction regimen in Asian living-donor kidney recipients is unclear.

Methods: This is a pilot study in which 36 consecutive patients undergoing living-donor kidney transplantation were randomly assigned to receive either 4.5 mg/kg (n = 19) or 6.0 mg/kg (n = 17) of ATG; all patients had corticosteroid withdrawal within 7 days. The primary end point was a composite of biopsy-proven acute rejection, de novo donor-specific antibody formation, and graft failure.

Results: At 12 months post-transplant, biopsy-proven acute rejection was more common in the ATG4.5 group (21.1%) than in the ATG6.0 group (0%)(P = .048). Importantly, the rate of the composite end point was significantly higher in the ATG4.5 group (36.8% vs 0%)(P = .006). There were significant differences in neither the renal function nor adverse events between the two groups. One case of death-censored graft failure occurred in the ATG4.5 group and no mortality was observed overall. Compared with pre-transplantation, T cells, natural killer (NK) cells, and natural killer T (NKT) cells were significantly decreased in the first week post-transplantation except for B cells. Although T and NKT cells in both groups and NK cells in the ATG4.5 group had recovered to the pre-transplant levels, NK cells in the ATG6.0 group remained suppressed until six months post-transplant.

Conclusions: Compared with ATG 6.0 mg/kg, ATG 4.5 mg/kg with early corticosteroid withdrawal and low dose maintenance regimen was associated with higher rates of acute rejection in non-sensitized Asian living-donor kidney recipients.

Trial registration: ClinicalTrials.gov: NCT02447822.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antilymphocyte Serum*
  • Humans
  • Living Donors
  • Pilot Projects
  • Prospective Studies
  • Steroids
  • Tacrolimus*

Substances

  • Antilymphocyte Serum
  • Tacrolimus
  • Steroids

Associated data

  • ClinicalTrials.gov/NCT02447822

Grants and funding

Initials of the authors who received each award: DJ Han Grant numbers awarded to each author: THYMOL07047 The full name of each funder: Sanofi-Aventis Korea Company URL of each funder website: www.sanofi.co.kr Did the sponsors or funders play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript? No.