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J Nephropathol. Inpress.
doi: 10.34172/jnp.2022.17220
  Abstract View: 1498

Case Report

Tocilizumab in a patient affected by chronic active antibody mediated rejection; histological improvement, reduction of proteinuria and renal function stabilization

Laura Panaro* ORCID logo, Matteo Trezzi, Michela Ardini, Michele Marchini, Marco Delsante, Davide Rolla

1 Divisione di Nefrologia , Dialisi e Trapianto, Ospedale Civile Sant’Andrea di La Spezia, La Spezia, Italy
2 Divisione di Nefrologia , Azienda Ospedaliera Universitaria di Parma, Parma, Italy
*Corresponding Author: Email: laura.panaro@asl5.liguria.it

Abstract

Introduction: Chronic active antibody-mediated rejection (cAMR) is a significant and rapid destructive form of allograft rejection and it is related to donor specific antibodies (DSA). Interleukin 6 (IL-6) plays an important role in mediating the allograft rejection by promoting CD4+ T cells differentiation to Th17 phenotype while inhibiting Treg. Tocilizumab is a humanized monoclonal antibody directed to IL-6 receptor (IL6-R). The aim of the study is to demonstrate the efficacy of tocilizumab as rescue therapy for cAMR.

Case Presentation: A 50-year-old man with Alport syndrome and with positive DSA against B7 e B55 underwent a second kidney transplant (HLA 2 mismatch). He received thymoglobulin and three plasma exchanges as induction therapy. Proteinuria (1-1.3 g/24 h) and decline in kidney function (serum creatinine; 1.5 mg/dL) appeared at 9 months. Kidney biopsy showed endocapillary proliferation, mononuclear cells infiltration, glomerular basal membrane duplication and tubulitis suggestive of cAMR. The patient has been treated with tocilizumab (6 mg/kg/mon) for six months. Reduction of proteinuria (0.6 g/24 h) and mild improvement of kidney function (serum creatinine; 1.3 mg/dL) were observed after tocilizumab treatment. A second biopsy revealed a significant decrease of glomerulitis and peritubular capillaritis. A significant reduction in DSA was detected.

Conclusion: Inhibition of the IL-6 receptor by tocilizumab may represent a novel and cheering approach to treat cAMR.


Implication for health policy/practice/research/medical education: Chronic active antibody-mediated rejection (cAMR) is a significant and rapid destructive form of allograft rejection, where IL-6 plays an important role. We report a case of 50-year-old man with kidney transplant, who developed cAMR and has been treated with tocilizumab, a humanized monoclonal antibody directed to IL-6 receptor (IL-6R). We demonstrate its efficacy as new treatment strategy in patients who are resistant to current therapies. Please cite this paper as: Panaro L, Trezzi M, Ardini M, Marchini M, Delsante M, Rolla D. Tocilizumab in a patient affected by chronic active antibody-mediated rejection; histological improvement, reduction of proteinuria and renal function stabilization. J Nephropathol. 2021;10(x):exx. DOI: 10.34172/jnp.2021.xx.
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Submitted: 27 Feb 2021
Accepted: 10 Jun 2021
ePublished: 16 Jul 2021
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