Genetic Factors and Clinical Manifestations of Renal Thrombotic Microangiopathy in Severe Hypertension

Relevance Renal thrombotic microangiopathy (TMA) in malignant arterial hypertension (MAH) often leads to end-stage renal failure [1]. Traditional treatment aimed only at lowering blood pressure is often insufficiently effective [2, 3]. The possible role of dysregulation of the complement system (CS) in the pathogenesis of TMA opens up new treatment prospects. Objective To study the clinical picture and genetic profile of CS in patients with renal TMA against the background of MAH. Material and methods A total of 28 patients with verified renal TMA and MAH were examined. Patients with signs of atypical hemolytic uremic syndrome (aHUS) were excluded. Molecular genetic analysis (exome sequencing) was performed to identify genetic defects of SC [4]. Results In 25% of patients (7 people), rare genetic variants of the SC genes associated with aHUS were detected, including defects in the CFI, C3, CD46, CFHR4, CFHR5 genes and chromosomal deletions affecting the CFH genes (CFHR1, CFHR3). Conclusion In a significant proportion of patients with renal TMA in RAG, even in the absence of hematological signs of aHUS, genetic defects of the SC are detected. Genetic testing of the SC in combination with morphological analysis of the renal biopsy is necessary to clarify the nature of TMA and the choice of therapy, including complement blocking. Keywords: renal thrombotic microangiopathy (TMA); complement system; genetic defects of the complement system