Elsevier

Transplantation Proceedings

Volume 48, Issue 9, November 2016, Pages 3106-3108
Transplantation Proceedings

Original contributions: Case reports
Kidney
Belatacept and Eculizumab for Treatment of Calcineurin Inhibitor-induced Thrombotic Microangiopathy After Kidney Transplantation: Case Report

https://doi.org/10.1016/j.transproceed.2016.04.005Get rights and content

Highlights

  • Thrombotic microangiopathy (TMA) after renal transplantation is a rare cause of early graft loss attributed to calcineurin inhibitors (CNI).

  • Complement-mediated endothelial destruction occurs in CNI-associated TMA.

  • Treatment of CNI-associated TMA with eculizumab and belatacept is described.

Abstract

Thrombotic microangiopathy (TMA) after kidney transplantation is an uncommon and challenging cause of graft dysfunction and is associated with early graft loss. An idiosyncratic endothelial reaction to calcineurin inhibitors (CNIs) has been implicated as a frequent cause of TMA. This reaction is marked by uncontrolled activation of complement and subsequent cellular destruction. Usual therapy consists of withdrawal of the inciting drug and plasmapheresis to minimize levels of circulating complement. Recently, eculizumab, a monoclonal antibody to complement component C5, has been used for the treatment of atypical hemolytic uremic syndrome. Belatacept, an inhibitor of T cell costimulatory protein CTLA-4 has been used in immunosuppression strategies aimed at minimization of CNI. Here we report the first case of treatment of CNI-associated TMA/hemolytic uremic syndrome with withdrawal of tacrolimus and initiation of both belatacept and eculizumab. The case describes a favorable clinical course for both graft and patient, and is accompanied by a review of the literature.

Section snippets

Case Report

A 22 year-old male presented with renal disease secondary to hemolytic uremic syndrome (HUS) associated with enteropathogenic Escherichia coli infection at age 2 years. He underwent living-related kidney transplantation at age 3 years, suffered graft loss at age 12 years, and subsequently underwent a second living-related kidney transplantation the following year. This allograft was lost to chronic antibody-mediated rejection at age 21 years. Both grafts were lost due to chronic allograft

Discussion

The case presented here represents the first description of the combined use of belatacept and eculizumab for CNI-induced TMA. TMA is a severe complication of renal allotransplantation, often occurring within the first 6 months after operation. Pathologically, TMA is marked by vascular damage within the arterioles and glomeruli with intraluminal thrombosis and arteriolar wall thickening.

TMA is categorized as de novo or recurrent after transplantation. De novo TMA is less common and is defined

References (8)

There are more references available in the full text version of this article.

Cited by (13)

  • Renal Transplant Immunosuppression in Patients With Hemolytic Uremic Syndrome: Four Case Reports

    2018, Transplantation Proceedings
    Citation Excerpt :

    Although there are no clearly established guidelines in transplantation immunosuppression in patients with aHUS, the use of eculizumab pre- and post-transplantation is considered beneficial due to its mechanism of blocking the C5 fraction of the complement [16]. There are already some published cases [8,17,18] with a good evolution. In the available studies, a high percentage of re-transplantations is highlighted, possibly due to lower survival of the graft in these patients with a more potent induction because of the greater risk of associated rejection and some of them already hyperimmunized.

  • Post-transplant Intestinal Thrombotic Microangiopathy

    2023, Digestive Diseases and Sciences
View all citing articles on Scopus
View full text