Молодежный инновационный вестник

2415-7805

Федеральное государственное бюджетное образовательное учреждение высшего образования "Воронежский государственный медицинский университет имени Н.Н. Бурденко" Министерства здравоохранения Российской Федерации

10655

Conference Proceedings

A New Method of Desensitization in Organ Transplantation – Use of Imlifidase

Gusev

Илья Vladimirovich

ilagusev67882@mail.ruhttps://orcid.org/0009-0002-1271-2198Voronova

Anna Alexandrovna

voronova.anna1505@gmail.comhttps://orcid.org/0009-0009-7155-8590

Burdenko Voronezh State Medical University

25042025

14S1336340

07032025

11032025

2025

Introduction. Hydronephrosis associated with uropelvic junction anomalies (UPJHN) is a pathological condition leading to progressive urinary outflow obstruction and renal tissue atrophy, which can result in chronic kidney failure and various complications. Early diagnosis and timely intervention are crucial for preventing complications such as urinary tract infections, pyelonephritis, and renal hypertension. The aim of this study is to analyze the clinical presentation and symptoms of hydronephrosis caused by uropelvic junction anomalies, as well as to review modern diagnostic and treatment methods, including surgical intervention. The study utilizes data from relevant scientific publications, prenatal ultrasound screenings, and clinical observations, which help in developing effective patient management algorithms. Hydronephrosis in UPJHN can be asymptomatic or present with symptoms such as urinary tract infections, abdominal pain, hematuria, and elevated blood pressure. In severe cases, progression of kidney failure and development of urosepsis are observed, requiring surgical correction. Treatment includes conservative observation with regular monitoring and surgical intervention when indicated. Early diagnosis and timely surgical intervention are essential measures to prevent irreversible renal tissue changes and preserve kidney function.

Imlifidasekidney transplantationdonor-specific antibodiesantibody-dependent rejectiondesensitizationHLA incompatibilityimmunoglobulin Gimmunosuppressionimmunological risk

Имлифидазатрансплантация почкидонор-специфические антителаантителозависимое отторжениедесенсибилизацияHLA-несовместимостьиммуноглобулин Gиммуносупрессияиммунологический риск

Introduction. Transplantology is a branch of medicine that deals with organ, tissue, and cell transplantation, including issues of preservation, immunological compatibility, and prevention of transplant rejection. It plays a crucial role in treating patients with end-stage organ failure, significantly improving their quality and duration of life. More than 150,000 organ transplants are performed worldwide annually, with approximately 80,000 being kidney transplants. Despite advancements in immunosuppression and surgical techniques, the rate of adverse outcomes remains high. Acute rejection occurs in 1020% of patients within the first year post-transplantation, and antibody-mediated rejection (ABMR) is observed in 3050% of recipients with high levels of donor-specific antibodies (DSA). Chronic graft dysfunction, caused by both immunological and non-immunological factors, leads to graft loss within 10 years in 4050% of kidney transplant recipients, with five-year graft survival rates ranging from 60% to 90%. Imlifidase is a novel enzyme derived from Streptococcus pyogenes that has the ability to cleave all subclasses of human IgG. This makes it a promising agent for HLA desensitization in kidney transplantation and the treatment of antibody-mediated rejection. Clinical studies have confirmed that imlifidase rapidly degrades donor-specific anti-HLA antibodies, facilitating HLA-incompatible kidney transplantation. Based on these findings, the European Medicines Agency (EMA) granted conditional approval for the drug to desensitize kidney transplant recipients from deceased donors with a positive crossmatch test. The practical application of imlifidase requires consideration of several factors, including the kinetics of donor-specific antibody recovery after administration, the optimal timing of additional therapeutic monoclonal and polyclonal IgG antibodies, and the potential impact of the drug on crossmatch compatibility testing. These aspects are crucial for the effective use of imlifidase in clinical transplantation, enabling transplantation in highly sensitized patients with a high immunological risk. Objective of the Study. The aim of this study is to collect and analyze scientific research on the prospects of imlifidase use in transplantology. Materials and Methods. The study involved searching and analyzing contemporary publications on this topic. Results of the Study. To deeply understand the mechanism of action of imlifidase, it is essential first to examine the process of transplant rejection, which it influences. Graft rejection mediated by immunoglobulin G (IgG) is an antibody-dependent process characterized by vascular damage to the graft and organ dysfunction. The main mechanism involves the presence of donor-specific antibodies (DSA) of the IgG class, which recognize HLA antigens on the endothelium of the grafts blood vessels, triggering a cascade of immune reactions. IgG binding to antigens activates the classical complement pathway, leading to the formation of the membrane attack complex (MAC), endothelial cell damage, and inflammation. In addition to complement-dependent cytotoxicity (CDC), IgG participates in antibody-dependent cellular cytotoxicity (ADCC), attracting NK cells, macrophages, and neutrophils, which release pro-apoptotic mediators, contributing to graft damage. These processes result in endothelialitis, microangiopathy, and vascular thrombosis, leading to acute or chronic antibody-mediated rejection (ABMR), accompanied by progressive graft dysfunction and possible graft loss. The mechanism of action of imlifidase is based on the proteolytic cleavage of the heavy chains of all IgG subclasses, resulting in the loss of their effector functions. The inactivation of IgG eliminates their ability to mediate complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC), which is crucial for preventing antibody-mediated transplant rejection. Following intravenous administration, imlifidase rapidly inactivates circulating IgG, ensuring their complete elimination from plasma within 46 hours. Beyond the plasma pool, the enzyme degrades extravascular IgG, making it an effective desensitization agent for patients with high donor-specific antibody (DSA) titers. The drug enables HLA-incompatible kidney transplantation by temporarily reducing DSA levels, lowering the risk of hyperacute and acute antibody-mediated rejection. Pharmacokinetic studies have shown that the drug's peak effect lasts for 624 hours, after which IgG levels begin to gradually recover. Endogenous IgG synthesis resumes after 23 days, and within 23 weeks, IgG once again becomes the predominant immunoglobulin fraction, although its overall level remains below physiological norms for at least two months. Clinical studies have confirmed the safety and efficacy of imlifidase in highly sensitized patients awaiting transplantation. Its use allows for the rapid elimination of DSA, enabling organ transplantation in immunologically incompatible conditions. Lorant et al. presented the results of a Phase 2 study evaluating the safety, immunogenicity, pharmacokinetics, and efficacy of imlifidase in highly sensitized patients with end-stage CKD. The study included 8 patients with an average cPRA of 64%, who received two escalating doses of the drug over two days. All patients demonstrated IgG degradation with serum IgG levels 1% within 48 hours, remaining low until day 7. MFI values for class I and II anti-HLA antibodies significantly decreased. Anti-IdeS antibodies appeared within a week, peaking at two weeks. One patient who was offered a kidney transplant from a deceased donor successfully underwent transplantation after imlifidase treatment, which eliminated anti-HLA antibodies and allowed transplantation despite a positive crossmatch. The study showed that imlifidase is effective, safe, and well-tolerated in sensitized patients, providing a 7-day window for successful kidney transplantation from an HLA-incompatible donor. However, the drug's effect is temporary, requiring strict monitoring of antibody recovery dynamics and timely adjustments to immunosuppressive therapy to prevent rejection. No serious adverse reactions were observed, and all recipients had functioning grafts with an average follow-up of 235 days. The authors concluded that imlifidase is a promising desensitization option, offering patients a chance for life-saving kidney transplantation. Another study showed that 24 out of 25 patients successfully underwent kidney transplantation, with a mean eGFR of 58 30 ml/min/1.73 m at six months. Conclusion. Imlifidase is an effective desensitization agent for highly sensitized patients awaiting kidney transplantation, enabling successful transplantation even in cases of HLA incompatibility. However, its use is associated with several side effects, such as the rapid reappearance of donor-specific antibodies (DSA), which can lead to transplant rejection and the need for intensified immunosuppression, increasing the risk of infections and other complications. Additionally, the development of antibodies against IdeS limits the possibility of repeated drug administration. The use of imlifidase requires careful patient selection and strict monitoring of antibody recovery, as well as consideration of interactions with other therapeutic agents. Despite these challenges, clinical studies confirm the safety and efficacy of imlifidase when used correctly, providing patients with a chance for successful transplantation.

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