ATYPICAL HEMOLYTIC-UREMIC SYNDROME IN CHILDREN IN BELARUS AND THE FIRST USE OF COMPLEMENT BLOCKING TREATMENT THERAPIES

Atypical hemolytic uremic syndrome (aHUS) is one of the most complex and severe forms of thrombotic microangiopathy with an unfavorable outcome in its natural course. The purpose of this research was to study the epidemiology, demographics, course and outcomes of aHUS in comparison with patients with typical hemolytic uremic syndrome (tHUS) as well as to conduct a personal analysis of all cases of aHUS and evaluate the response to therapy, including comple-ment-blocking with Eculizumab. Materials and methods used: the study was longitudinal, obser-vational and included all 349 cases of HUS in children in Belarus in 2015-2023. A comparative analysis of demographic and clinical data, laboratory results and outcomes was performed in pa-tients with HUS hospitalized at the Center for Pediatric Nephrology and Renal Replacement Therapy of the Republic of Belarus (Minsk, Belarus). Results: of 349 HUS cases, the proportion of aHUS was 3,7% (13). Children with aHUS were older (4,6 (1,6; 6,7) v. 2,7 (1,7; 4,8) y/o with tHUS) due to the portion of patients older than 5 y/o (46%). In aHUS, severe central nervous system disorders were more often observed (62% v. 14%, p=0,002), the development of critical conditions requiring transfer to mechanical ventilation (39% v. 9%, p=0,006), prolonged anuria with the need for dialysis therapy in 100% of cases and severe adverse outcomes (death or end-stage renal disease) during natural course (66,0% v. 2,7%, p<0,001). The most common trigger for aHUS was acute intestinal infections in 54% of cases. A genetic study was performed in 9 (69%) children with aHUS and in 8 (89%) of them the CFHR3/CFHR1 deletions were detected: in 4 cases (3 hetero- and a single homozygous) and heterozygous pathogenic and probably patho-genic gene mutations, CFHR5 in 2 cases, CFH in a single case and combined CD46 and CFI in a single case as well. Antibodies to complement factor H were detected in 5 patients, 3 of which had a CFHR3/CFHR1 deletion. Therapy with a biosimilar of the original Eculizumab showed its effectiveness in aHUS: in 3 (100%) children it was possible to prevent the return of the disease in the kidney graft, in single patient who did not receive prophylaxis it was able to block the recur-rence of aHUS in the transplanted kidney while preserving its function, in 3 (100%) patients with late administration of treatment the urine output was restored after prolonged anuria (24, 33 and 59 days); in a single child with the antibody variant of aHUS, with early administration of the drug, renal function was preserved. No complications of complement blocking therapy were not-ed. Conclusions: the introduction into clinical practice of a biosimilar of the original Eculizumab in children in Belarus has significantly improved the outcomes and prognosis of the disease.