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P-18.19 Low dose (4.5 mg/kg) of Thymoglobulin is effective to control T cells but not B cells and CD56dimCD57+, CD56dimNKG2A+ natural killer cells resulting in de novo donor-specific antibody formation and acute rejection in non-sensitized living donor kidney recipients with early steroid withdrawal

Sung Shin, Korea

Asan Medical Center, University of Ulsan College of Medicine

Abstract

Low dose (4.5 mg/kg) of Thymoglobulin is effective to control T cells but not B cells and CD56dimCD57+, CD56dimNKG2A+ natural killer cells resulting in de novo donor-specific antibody formation and acute rejection in non-sensitized living donor kidney recipients with early steroid withdrawal

Youngmin Ko1, Hey Rim Jung1, Mi Joung Kim1, Yu-Mee Wee1, Monica Young Choi1, Hyunwook Kwon1, Dong Hyun Kim1, Seong Jun Lim1, Joo Hee Jung1, Young Hoon Kim1, Duck Jong Han1, Sung Shin1.

1Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

The optimal dose of Thymoglobulin as an induction regimen in Asian living donor kidney recipients has been rarely reported. Patients were randomly assigned to receive either 4.5 mg/kg (ATG4.5 group, n=19) or 6.0 mg/kg (ATG6.0 group, n=17) Thymoglobulin. 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, or graft failure. Until 49 months post-transplant, the rate of the composite end point was 47.4% in the ATG4.5 group whereas 17.6% in the ATG6.0 group. There was one case of death-censored graft failure in the ATG4.5 group whereas there was no mortality during the follow-up period (22 to 49 months). This study was ceased earlier than expected because we concerned about the more increasing risk of the composite end point in the ATG4.5 group. Compared to pre-transplantation, T (CD3+CD56-) cells, NK (CD3-CD56+) cells, and NKT (CD3+CD56+) cells were significantly decreased whereas B (CD19+) cells were not significantly affected by Thymoglobulin in the first week. Although T and NKT cells had recovered to the pre-transplant value in both groups, NK cells in the ATG6.0 were kept suppressed while NK cells in the ATG4.5 group had recovered to the pre-transplant value. Interestingly, CD56dimCD57+ cells were significantly increased whereas CD56dimNKG2A+ cells was significantly decreased in the ATG4.5 group compared with the ATG6.0 group until six months post-transplant. ATG 4.5 mg/kg induction and early corticosteroid withdrawal tended to increase the rate of de novo donor-specific antibody and biopsy-proven acute rejection. (ClinicalTrials.gov: NCT02447822)

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