Use of tocilizumab in treatment of chronic active antibody mediated kidney transplant rejection

Мұқаба

Дәйексөз келтіру

Толық мәтін

Ашық рұқсат Ашық рұқсат
Рұқсат жабық Рұқсат берілді
Рұқсат жабық Рұқсат ақылы немесе тек жазылушылар үшін

Аннотация

Objective: to evaluate the safety and efficacy of tocilizumab in the treatment of chronic active antibody-mediated kidney transplant rejection.

Material and methods: A prospective study of tocilizumab use in the treatment of morphologically verified chronic active antibody-mediated transplant rejection was conducted in 15 kidney recipients.

Results and conclusion: in recipients who lost their graft function during the observation period, a high chronicity index was found according to morphological examination of the graft. After administration of tocilizumab, a decrease in the level of microvascular inflammation was observed.

Толық мәтін

Рұқсат жабық

Авторлар туралы

Nadezhda Rapetskaya

Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology

Хат алмасуға жауапты Автор.
Email: n.rapetskaja@gmail.com
ORCID iD: 0009-0005-4560-1162

Nephrologist, Department of Transplant Nephrology

Белоруссия, Minsk

Kirill Komissarov

Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology; Belarusian State Medical University

Email: kirill_ka@tut.by
ORCID iD: 0000-0002-2648-0642

PhD (Med. Sci), Associate Professor, Head of the Department of Nephrology, Renal Replacement Therapy and Kidney Transplantation

Белоруссия, Minsk; Minsk

Margarita Dmitrieva

Belarusian State Medical University

Email: mvdmitieva@inbox.ru
ORCID iD: 0000-0002-2958-9424

PhD (Med. Sci), Associate Professor, Department of Pathological Anatomy and Forensic Medicine

Белоруссия, Minsk

Tatiana Liatkoyskaya

Belarusian State Medical University

Email: taletkovskaya@mail.ru
ORCID iD: 0000-0002-9381-2985

PhD (Med. Sci), Associate Professor, Head of the Department of Pathological Anatomy and Forensic Medicine

Белоруссия, Minsk

Aleh Kalachyk

Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology

Email: oleg_kalachik@hotmaill.com
ORCID iD: 0009-0002-6954-675X

DSc (Med Sci), Professor, Deputy Director for Medical Affairs

Белоруссия, Minsk

Әдебиет тізімі

  1. Einecke G., Reeve J., Gupta G. et al. Factors associated with kidney graft survival in pure antibody-mediated rejection at the time of indication biopsy: importance of parenchymal injury but not disease activity. Am. J. Transplant. 2021;21:1391–1401. doi: 10.1111/ajt.16161.
  2. Рапецкая Н.В., Комиссаров К.С., Дмитриева М.В., Летковская Т.А., Калачик О.В. Морфологическая структура поздней дисфункции почечного трансплантата. Клиническая нефрология. 2024;18(4):12–16. [Rapetskaya N.V., Komissarov K.S., Dmitrieva M.V., Liatkoyskaya T.A., Kalachyk A.V. Morphological structure of late kidney transplant dysfunction. Clinical Nephrology. 2024;18(4):12–16. (In Russ.)]doi: 10.18565/nephrology.2024.4.12-16.
  3. Sellarés J., de Freitas D.G., Mengel M., Reeve J., Einecke G., Sis B. et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am. J. Transplant. 2012;12:388–399. doi: 10.1111/j.1600-6143.2011.03840.x.
  4. Schinstock C.A., Mannon R.B., Budde K., Chong A.S., Haas M., Knechtle S. et al. Recommended treatment for antibody-mediated rejection after kidney transplantation: the 2019 Expert Consensus from the Transplantation Society Working Group. Transplantation. 2020;104(5):911–922. doi: 10.1097/TP.0000000000003096.
  5. Loupy A., Haas M., Roufosse C. et al. The Banff 2019 Kidney Meeting Report (I): updates on and clarification of criteria for T cell – and antibody-mediated rejection. Am. J. Transplant. 2020;20:2318–2331. doi: 10.1111/ajt.15898.
  6. Pineiro G.J., De Sousa-Amorim E., Sole M., Rios J., Lozano M., Cofan F. et al. Rituximab, plasma exchange and immunoglobulins: an ineffective treatment for chronic active antibody-mediated rejection. BMC Nephrol. 2018;19(1):261. doi: 10.1186/s12882-018-1057-4.
  7. Moreso F., Crespo M., Ruiz J.C., Torres A., Gutierrez-Dalmau A., Osuna A. et al. Treatment of chronic antibody-mediated rejection with intravenous immunoglobulins and rituximab: a multicenter, prospective, randomized, double-blind clinical trial. Am. J. Transplant. 2018;18(4):927–935. doi: 10.1111/ajt.14520.
  8. Eskandary F., Regele H., Baumann L., Bond G., Kozakowski N., Wahrmann M. et al. A randomized trial of bortezomib in late antibody-mediated kidney transplant rejection. J. Am. Soc. Nephrol. 2018;29(2):591–605. doi: 10.1681/ASN.2017070818.
  9. Kulkarni S., Kirkiles-Smith N.C., Deng Y.H., Formica R.N., Moeckel G., Broecker V. et al. Eculizumab therapy for chronic antibody-mediated injury in kidney transplant recipients: a pilot randomized controlled trial. Am. J. Transplant. 2017;17(3):682–691. doi: 10.1111/ajt.14001.
  10. Tanaka T., Kishimoto T. The biology and medical implications of interleukin-6. Cancer Immunol. Res. 2014;2:288–294. doi: 10.1158/2326-6066.CIR-14-0022.
  11. Jordan S.C., Choi J., Kim I., Wu G., Toyoda M., Shin B. et al. Interleukin-6, a cytokine critical to mediation of inflammation, autoimmunity and allograft rejection: therapeutic implications of IL-6 receptor blockade. Transplantation. 2017;101:32–44. doi: 10.1097/TP.0000000000001452.
  12. Sethi S, D’Agati V.D., Nast C.C., Fogo A.B., De Vriese A.S., Markowitz G.S.,et al. A proposal for standardized grading of chronic changes in native kidney biopsy specimens. Kidney Int. 2017;91(4):787–789. Doi: 10.1016/ j.kint.2017.01.030.
  13. Pöge U., Gerhardt T., Palmedo H., Klehr H.U., Sauerbruch T., Woitas R.P. MDRD equations for estimation of GFR in renal transplant recipients. Am. J. Transplant. 2005;5(6):1306–1311. doi: 10.1111/j.1600-6143.2005.00861.x.
  14. Choi J., Aubert O., Vo A., Loupy A., Haas M., Puliyanda D. et al. Assessment of tocilizumab (anti-interleukin-6 receptor monoclonal) as a potential treatment for chronic antibody-mediated rejection and transplant glomerulopathy in HLA-sensitized renal allograft recipients. Am. J. Transplant. 2017;17:2381–2389. doi: 10.1111/ajt.14228.
  15. Lavacca A., Presta R., Gai C., Mella A., Gallo E., Camussi G. et al. Early effects of first-line treatment with anti-interleukin-6 receptor antibody tocilizumab for chronic active antibody-mediated rejection in kidney transplantation. Clin. Transplant. 2020;34(8):e13908. doi: 10.1111/ctr.13908.
  16. Massat M., Congy-Jolivet N., Hebral A.L., Esposito L., Marion O., Delas A. et al. Do anti-IL-6R blockers have a beneficial effect in the treatment of antibody-mediated rejection resistant to standard therapy after kidney transplantation? Am. J. Transplant. 2021;21:1641–1649. Doi: 10.1111/ ajt.16391.
  17. Noble J., Comai G., Corredetti V., Laamech R., Dard C., Jouve T. et al. Tocilizumab-based treatment of microvascular inflammation in kidney transplant recipients: a retrospective study. Transpl. Int. 2025;38:14502. doi: 10.3389/ti.2025.14502.
  18. Cornell L.D., Helanterä I. Exploring microvascular inflammation and the spectrum of antibody-mediated rejection. Am. J. Transplant. 2025;25(1):9–12. doi: 10.1016/j.ajt.2024.12.005.
  19. Redfeld R.R., Ellis T.M., Zhong W. et al. Current outcomes of chronic active antibody-mediated rejection — a large single center retrospective review using the updated Banff 2013 criteria. Hum. Immunol. 2016;77:346–352. doi: 10.1016/j.humimm.2016.01.006.
  20. Khairallah P., Robbins-Juarez S., Patel S., Shah V., Toma K., Fernandez H. et al. Tocilizumab for the treatment of chronic antibody mediated rejection in kidney transplant recipients. Clin. Transplant. 2023;37(1):e14853. doi: 10.1111/ctr.14853.
  21. Cabezas L., Jouve T., Malvezzi P., Janbon B., Giovannini D., Rostaing L., Noble J. Tocilizumab and active antibody-mediated rejection in kidney transplantation: a literature review. Front. Immunol. 2022;13:839380. doi: 10.3389/fimmu.2022.839380.

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Әрекет
1. JATS XML
2. Fig. 1. Dynamics of the MVI index in group 2 after treatment with tocilizumab

Жүктеу (49KB)
3. Fig. 2. Dynamics of laboratory parameters in group 2 after treatment with tocilizumab: a)<зTeatinine, b) GFR, c) proteinuria, d) anti-Hb'I antibodies

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