Case report: Eculizumab plus obinutuzumab induction in a deceased donor kidney transplant recipient with DEAP-HUS

Abstract

The wide-spread use of the anti-complement component 5 monoclonal antibody (moAb) eculizumab has greatly reduced the incidence of relapsing atypical hemolytic uremic syndrome (aHUS) after kidney transplantation (KT). However, the optimal management of aHUS transplant candidates with anti-Complement Factor H (CFH) antibodies remains debated. In these patients, the benefits of chronic eculizumab administration should be weighed against the risk of fatal infections, repeated hospital admissions, and excessive costs. We report the case of a 45-year-old female patient with CFHR1/CFHR3 homozygous deletion-associated aHUS who underwent deceased-donor KT despite persistently elevated anti-CFH antibody titers. As induction and aHUS prophylaxis, she received a combination of eculizumab and obinutuzumab, a humanized type 2 anti-CD20 moAb. The post-operative course was uneventful. After 1-year of follow-up, she is doing well with excellent allograft function, undetectable anti-CFH antibodies, sustained B-cell depletion, and no signs of aHUS activity. A brief review summarizing current literature on the topic is also included. Although anecdotal, our experience suggests that peri-operative obinutuzumab administration can block anti-CFH antibodies production safely and effectively, thus ensuring long-lasting protection from post-transplant aHUS relapse, at a reasonable cost. For the first time, we have demonstrated in vivo that obinutuzumab B-cell depleting properties are not significantly affected by eculizumab-induced complement inhibition.

Current Status Regarding Immunosuppressive Treatment in Patients after Renal Transplantation

“…It should be added that Muromonab-CD3, often referred to as OKT3, was previously used to treat acute cellular rejection after solid organ transplantation. However, due to hepatotoxic properties, the mentioned drug was withdrawn from use in 2010 [ 27 , 28 , 29 , 30 ].…”

“…Current protocols are usually based on triple-drug therapy containing calcineurin inhibitors, corticosteroids, and antiproliferative drugs. In addition, mono- or polyclonal antibodies are also used in induction therapy [ 28 ]. It is important to note that the intensity of immunosuppression is determined by immunologic risk, and because of this, patients are classified according to variables related to immunologic risk.…”

Immunosuppressive Therapy and Nutritional Status of Patients after Kidney Transplantation: A Protocol for a Systematic Review

“…It is important to emphasiz that the use of appropriately tailored and consistently administered immunosuppressive therapy is linked to enhanced graft survival [7]. Secondly, the choice of drug and treatment regimen depends on several factors such as prognostic factors depending on the donor and recipient of the organ, etiology of the disease, duration since transplantation (whether it is induction or maintenance), condition of the graft, as well as the interaction of the selected immunosuppressive drug with other drugs used and expected side effects [3,14]. What is important, the cost of treatment should also be considered [3].…”

“…These strategies have been devised by combining drugs with diverse mechanisms of action effectively. The gold standard immunosuppressive regimen for kTx recipients involves the use of several medications that target various mechanisms and pathways, of which the five main ones include: (1) Calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus, (2) Mammalian target of rapamycin (mTOR) inhibitors (sirolimus and everolimus), (3) Antiproliferatives like azathioprine and mycophenolic acid derivatives, (4) Glucocorticosteroids, (5) Biological immunosuppressive agents [14]. Contemporary protocols typically involve triple-drug therapy, which includes CNIs, corticosteroids, and antiproliferative drugs.…”

“…CsA biochemically is a cyclic peptide comprising eleven amino acids. Its metabolism primarily takes place via the cytochrome P (CYP) 450A3 enzyme system, with less metabolism occurring in the gastrointestinal tract and kidneys [14]. Tac seems to be much stronger compared to CsA [16].…”