АТИПИЧНЫЙ ГЕМОЛИТИКО-УРЕМИЧЕСКИЙ СИНДРОМ У ДЕТЕЙ, АССОЦИИРОВАННЫЙ С АНТИТЕЛАМИ К ФАКТОРУ Н: КЛИНИЧЕСКИЕ ПРОЯВЛЕНИЯ, ДИАГНОСТИКА И ЛЕЧЕНИЕ

Abstract

Atypical hemolytic uremic syndrome (aHUS) refers to one of the forms of thrombotic microangiopathy occurring with preferred damage to the kidneys. About 10% of all cases of aHUS in children are aHUS associated with antibodies to complement factor H (CFH-Ab-aHUS). In 90% of cases CFH-Ab-aHUS is represented by DEAP-HUS (Deficiency of Complement Factor H Related (CFHR) plasma proteins and Autoantibody Positive Hemolytic Uremic Syndrome) with a predominant deficiency of CFHR1, most often due to a homozygous deletion of CFHR3/CFHR1. CFH-Ab-aHUS is characterized by the age of onset of the disease of 4 to 12 years old; the presence of a prodrome, more often associated with gastrointestinal disorders such as vomiting and abdominal pain, less often diarrhea; relapsing course with a high risk in the first 6 months from the onset of the disease, a high proportion of adverse outcomes: death of the patient or development of end stage chronic kidney disease (CKD). Determination of the CFH-Ab titer should be performed in all children with HUS, and in case of their increase, regularly monitored during treatment. Treatment begins with eculizumab or its biosimilar until a CFH-Ab titer is obtained and, if CFH-Ab-aHUS is confirmed, it is necessary to switch to intensive plasma exchanges in combination with immunosuppressive therapy. If there are contraindications to immunosuppressive therapy or if there is no effect from it, if plasma exchanges are impossible or ineffective, if significant mutations in complement regulator genes are detected, it is necessary to continue or return to complement blocking therapy. After achieving remission of the disease, long-term monitoring of patients is required to control residual effects on the kidneys (hematuria, proteinuria, CKD) and the cardiovascular system (arterial hypertension, left ventricular myocardial hypertrophy). In patients who have reached the end stage of CKD, it is mandatory to determine the anti-CFH titer and conduct a molecular genetic research in order to determine the risks of the disease returning to the kidney graft and the need for prophylactic therapy with eculizumab or its biosimilar before and after the surgical intervention.