A case report of atypical hemolytic-uremic syndrome treatment with the first Russian eculizumab in adult patient
- Urology & Nephrology Open Access Journal
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Lavrishcheva IV,1 Jakovenko AA,2 Kudlay DA3
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Abstract
Atypical hemolytic uremic syndrome (aHUS) is a chronic genetically-mediated systemic disease caused by uncontrolled activation of the alternative complement pathway that leads to generalized thrombosis of the microcirculatory vessels (complement-mediated thrombotic microangiopathy, TMA). Plasma therapy was long considered the first-line treatment of aHUS. In the early 2000s, considerable progress in the understanding of aHUS pathophysiology and its treatment was achieved, leading to the emergence of innovative therapeutic approaches. An original drug of eculizumab has shown high efficacy in aHUS patients associated with hematological remission, including renal function recovery in some cases.
Study purpose: To assess the efficacy and safety of the first Russian eculizumab biosimilar for the treatment of aHUS in adults.
Patients and methods: A clinical observation of one adult patient with aHUS was held.
Results: A 46-year-old patient has a history of hypertension since 2012 and maximum BP of 230/130 mm Hg. In 2016, newly diagnosed azotemia was identified (blood creatinine —140 μmol/L, GFR by EPI—54 mL/min/1.73 m2). In 2018, the patient suffered an acute cerebrovascular accident in the vertebrobasilar area. On the date of admission to the Almazov National Medical Research Center the blood test showed: creatinine —60 μmol/L (GFR by EPI —28 mL/min/1.73 m2), urea —11.52 mmol/L, LDH—130 U/L, complement system C3—1.32 g/L, ?4—0.37 g/L, haemoglobin—144 g/L, platelets—302*109/L; urinalysis showed: daily protein loss—2.6 g/day, RBC—0–1 per HPF. Taking into account the kidney damage, the renal fine-needle aspiration biopsy was performed, revealing histopathological findings typical of chronic thrombotic microangiopathy, arteriolar arteriosclerosis of extreme severity with total or subtotal luminal occlusion, extensive secondary perihilar segmental glomerulosclerosis (27%) and global glomerulosclerosis (55%). According to the study results, the secondary genesis of TMA was ruled out, as well as STEC-HUS and thrombotic thrombocytopenic purpura (TTP), systemic diseases (systemic lupus erythematosus, antiphospholipid syndrome (APS), and systemic sclerosis), malignancies, HIV infection, sepsis, malignant hypertension, adverse drug events, or disseminated intravascular coagulation (DIC). Plasma ADAMTS13 levels were also assessed. Its activity was 64% (normal range 93–113%) of ADAMTS13 activity in the control plasma, thus the diagnosis of thrombocytopenic purpura was ruled out. Due to the absence of anti-CFH-antibodies, the antibody origin of aHUS was also ruled out.
To assess the contribution of additional factors promoting the development of TMA, the polymorphism of haemostasis genes was studied to reveal homozygous genotypes of platelet collagen receptors (ITGA2: 807 ?/?), heterozygous genotypes of fibrinogen genes (FGB: 455 G/?), folate cycle enzymes (methylenetetrahydrofolate reductase (MTHFR: 677 C/T), methionine synthase (MTR: 2756 A/G (D919G)), responsible for a pronounced tendency towards hyperhomocysteinemia. In the clinical case the diagnosis of aHUS was obvious, which was supported by the classical symptom cluster of TMA and histopathological verification in the absence of data suggestive of other pathological conditions. The peculiarity of this clinical case is the late diagnosis, long-standing course, and severity (complications such as an acute cerebrovascular accident in the vertebrobasilar area, target lesions, kidneys in particular). Taking into account the primary diagnosis, treatment with a standard dose of eculizumab was initiated. After three months of treatment, the patient was switched to therapy with the first Russian eculizumab biosimilar. After the switch from the original drug, the therapy with the biosimilar continued a positive trend including a gradual decline in azotemia level (blood creatinine—115 μmol/L (GFR by EPI—65 mL/min/1.73 m2), blood urea—6.90 mmol/L), proteinuria (daily protein loss—0.6 g/day). BP was also normalized. No adverse events associated with the therapy were observed.
Conclusion: Based on the evidence obtained, the first Russian eculizumab demonstrated its high efficacy and safety for the treatment of an adult patient with aHUS.
Keywords
diagnosis, long-standing course, segmental glomerulosclerosis, global glomerulosclerosis, vertebrobasilar area, target lesions, kidneys