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Single-dose antithymocyte globulin in standard immunological risk kidney transplant recipients: efficacy and kinetics of peripheral blood CD3+ T lymphocyte modulation

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Abstract

Background

Polyclonal anti-T cell antibodies (ATG or thymoglobulin®) are used as induction therapy in kidney transplant recipients. This study evaluates the safety, efficacy, and CD3+ T lymphocyte modulation of two ATG regimens.

Methods

The trial included two cohorts of kidney transplant recipients that were followed for one year. The study group, including standard immunological risk recipients, received one 3 mg/kg dose of ATG. The comparator group, including standard and high immunological risk kidney transplant recipients, received a fractionated dose regimen (up to four 1.5 mg/kg doses). Patient and graft outcomes and the kinetics of CD3+ T lymphocyte modulation in the peripheral blood were evaluated.

Results

One hundred kidney transplant recipients were included in each group. The one-year incidence of treated acute rejection, and patient and graft survival did not differ between groups. Bacterial infections were significantly more frequent in fractionated-dose group patients (66% versus 5%; P = 0.0001). At one-year follow-up, there was no difference in the incidence of cytomegalovirus infection (P = 0.152) or malignancies (P = 0.312). CD3+ T lymphocyte immunomodulation in the single-dose group was more effective in the first two days after transplantation. After the third post-transplant day, CD3+ T lymphocyte modulation was more efficient in the fractionated dose group.

Conclusion

Both regimens resulted in low rejection rates and equivalent survival. The single and reduced dose regimen protects from the occurrence of bacterial infections. CD3+ T lymphocyte modulation occurred with different kinetics, although it did not result in distinct outcomes.

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Data availability

Data is available upon reasonable request.

Abbreviations

AKI:

Acute kidney injury

AR:

Acute rejection

ATG:

Polyclonal anti-T cell antibodies

CD3+ TCL:

CD3+ T cell lymphocytes

CIT:

Cold ischemia time

CKD:

Chronic kidney disease

CMV:

Cytomegalovirus

CMV qPCR:

Cytomegalovirus quantitative polymerase chain reaction

DGF:

Delayed graft function

DSA:

Donor-specific antibodies

ECD:

Expanded criteria donor

eGFR:

Estimated glomerular filtration rate

FD:

Fractionated dose

HLA:

Human leukocyte antigens

KDPI:

Kidney Donor Profile Index

KDRI:

Kidney Donor Risk Index

KT:

Kidney transplant

KTR:

Kidney transplant recipient

MFI:

Median fluorescence intensity

MM:

Mismatch

MPA:

Mycophenolic acid

POD:

Postoperative day

PRA:

Panel reactive antibodies

SD:

Single dose

TAC SL:

Tacrolimus serum level

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Authors and Affiliations

  1. Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Fabiani P. Machado, Nicole Rauber, Alessandra R. Vicari, Andrea C. Bauer & Roberto C. Manfro

  2. Division of Nephrology, Hospital de Clínicas de Porto Alegre, St. Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-903, Brazil

    Alessandra R. Vicari, Andrea C. Bauer & Roberto C. Manfro

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Contributions

MPF, RN, VRA, BCA, MCR were involved in research design, participated in data analysis, wrote, and revised of the manuscript, final approval to be published, and accountable for all aspects of the work.

Corresponding author

Correspondence to Roberto C. Manfro.

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Conflict of interest

We have read and understood Journal of Nephrology's policy on disclosing conflicts of interest and declare that we have none.

Ethical approval

The ethics committee approved the study under registration CAAE ID: 38361620000005327. The study is registered in the Clinical trials registry (ClinicalTrials.gov—NCT04835948).

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The study was carried out in accordance with the Declaration of Helsinki in human research.

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Data sharing anonymized data will be shared upon reasonable request to the corresponding author.

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Machado, F.P., Rauber, N., Vicari, A.R. et al. Single-dose antithymocyte globulin in standard immunological risk kidney transplant recipients: efficacy and kinetics of peripheral blood CD3+ T lymphocyte modulation. J Nephrol (2023). https://doi.org/10.1007/s40620-023-01792-9

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