Clinical characteristics and genetic profile of complement system in renal thrombotic microangiopathy in patients with severe forms of arterial hypertension; [Клиническая характеристика и генетический профиль системы комплемента при почечной ТМА у пациентов с тяжелыми формами артериальной гипертонии]

Background. The spectrum of diseases characterized by the development of renal thrombotic microangiopathy (TMA) encompasses the malignant hypertension (MHT). TMA in MHT has conventionally been regarded as a variation of secondary TMA, the treatment of which is restricted to the stabilization of blood pressure levels, a measure that frequently fails to prevent the rapid progression to end-stage renal disease in patients. Nevertheless, there exists a rationale to suggest that, in certain instances, endothelial damage in MHT might be rooted in the dysregulation of the complement system (CS), thereby presenting potential opportunities for the implementation of complement-blocking therapy. Aim. To study clinical manifestations and genetic profile of CS in patients with morphologically confirmed renal TMA combined with severe AH. Materials and methods. 28 patients with morphologically verified renal TMA and severe AH were enrolled to the study. Patients with signs of microangiopathic hemolysis and thrombocytopenia were not included in the study due to possible compliance with the criteria for atypical hemolytic uremic syndrome (aHUS). The prevalence of rare genetic defects (GD) of the CS was assessed by molecular genetic analysis (search for mutations in the clinically significant part of the human genome – exome) by next-generation sequencing technology (NGS). Results. GD of CS were detected in a quarter of patients. Rare genetic variants classified as “likely pathogenic” including defects in CFI, C3, CD46, CFHR4, CFHR5 genes were detected in five cases. Two patients were found to have chromosomal deletions containing CFH-related proteins genes (CFHR1, CFHR3). Conclusion. Rare variants of CS genes linked to aHUS were found in 25% of patients with renal TMA, the genesis of which was originally thought to be secondary and attributed to MHT, with partial or complete absence of hematological manifestations of microangiopathic pathology. The key to confirming TMA associated with MHT, particularly in the absence of microangiopathic hemolysis and thrombocytopenia, elucidating its nature, and potentially effective complement-blocking therapy in patients with GD of CS, appears to be a genetic study of CS combined with a morphological study of a renal biopsy. © 2024 Consilium MediCum. All rights reserved.

Авторы
Akaeva M.I. , Kozlovskaya N.L. , Bobrova L.A. , Vorobyeva O.A. , Stoliarevich E.S. , Shatalov P.A. , Smirnova T.V. , Anan'eva A.O.
Номер выпуска
6
Язык
Русский
Страницы
571-579
Статус
Опубликовано
Том
96
Год
2024
Организации
  • 1 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
  • 2 Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russian Federation
  • 3 Patrice Lumumba People’s Friendship University of Russia, Moscow, Russian Federation
  • 4 Yeramishantsev City Clinical Hospital, Moscow, Russian Federation
  • 5 National Center for Clinical Morphological Diagnostics, Saint Petersburg, Russian Federation
  • 6 Russian University of Medicine, Moscow, Russian Federation
  • 7 City Clinical Hospital №52, Moscow, Russian Federation
  • 8 National Medical Research Radiological Centre, Obninsk, Russian Federation
  • 9 Krasnov Research Institute of Eye Diseases, Russiа, Moscow, Russian Federation
  • 10 Mariinsky City Hospital, Saint Petersburg, Russian Federation
Ключевые слова
atypical hemolytic uremic syndrome; complement genes; complement system; malignant hypertension; thrombotic microangiopathy
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