Atypical hemolytic-uremic syndrome (aHUS) is an ultra-rare life-threatening disease from the group of thrombotic microangiopathies (TMA) with genetic predisposition factors associated with uncontrolled activation of the alternative complement pathway. In 10% of cases aHUS is acquired and associated with antibodies to factor H (CFH-Ab-aHUS), among which 90% of cases are also determined by a deficiency of plasma proteins related to factor H (CFHR). Information on the course, therapeutic approaches and outcomes of CFH-Ab-aHUS varies Worldwide and is presented by series of clinical observations. The purpose of the research was to determine the patterns of the course and outcomes of CFH-Ab-aHUS to substantiate methods of effective treatment and improve prognosis. Methods used: retro- and prospective analysis of the course and outcomes of CFH-Ab-aHUS in 43 patients in Jan. 2010-Feb. 2022. The sample is continuous. In the development of microangiopathic hemolytic anemia (MAHA), thrombocytopenia and acute kidney injury (AKI), the diagnosis of CFH-Ab-aHUS was established after exclusion of other forms of TMAs and determination of immunoglobulin class G (IgG) in serum against factor H by enzyme-linked immunosorbent assay (ELISA-VIDITEST anti-complement factor H, Czech Republic). In 41 cases molecular genetic study by NGS (next generation sequencing) for aHUS panel and Sanger sequencing were performed. Results: the incidence of CFH-Ab-aHUS was 20.6% among all cases of aHUS. In 88.4% of children the disease debuted at the age of above 4 y/o. It was associated with a trigger (infections, vaccination, trauma, etc.) in 76.7% of cases. The median (Me) level of antibodies to factor H was 12400 [4187; 22181] AU/ml, which was more than 8 times higher than the normal upper limit. The acute period was characterized by the development of the TMA triad (MAGA, thrombocytopenia, AKI) in 100%, hemorrhagic syndrome (69.8%), arterial hypertension (69.8%), C3 consumption (77.8%) and dysfunction of more than 2 systems (83.7%). Neoliguric form of AKI was diagnosed in 44.2%, cardiac involvement in 65.1%, CNS in 55.8%, GI in 51.2%, pulmonary in 23.3%, and visual organ in 16.3% of cases. CFHR1/CFHR3 deletions were found in 87.8% (36/41) of cases (77.8% homozygous/ 22.2% heterozygous). Relapses were noted in 34.9%. Remission of CFH-Ab-aHUS was achieved in 11.6% of cases using plasma therapy and immunosuppressants, in 88.4% - with complement-blocking therapy (eculizumab). The outcome of the disease was characterized by the development of arterial hypertension (65.1%), CKD (60.5%), hypertrophic (25.6%) and dilated cardiomyopathy (16.3%). Conclusion: thus, in the Russin pediatric population with aHUS, every fifth child is diagnosed with CFH-Ab-aHUS associated with a risk of recurrence in every third child. The most important components of the management of patients with CFH-Ab-aHUS are its timely diagnosis and initiation of pathogenetic therapy (plasma therapy with immunosuppressants/eculizumab).

Atypical hemolytic uremic syndrome (aHUS) is a life-threatening disease caused by dysregulation of the alternative complement pathway as a result of mutations in complement genes or the formation of antibodies (AB) to some of the complement factors. Identification of the gene mutations incidence and the corresponding phenotypic features in pediatric patients with aHUS in Russia is aimed at improving the diagnosis and prognosis of the disease as well as treatment tactics planning for patient management. The purpose of this research was to determine the patterns of progression, prognosis and outcomes of aHUS in children depending on their genetic profile. Materials and methods used: the Article represents data from a retro- and prospective analyses of the characteristics of the course of aHUS in 172 children depending on their genetic profile performed in Jan. 2012-Feb. 2022. The sporadic form of aHUS was diagnosed after exclusion of the other forms of thrombotic microangiopathy (TMA), the familial form (in cases with the familial records), the acquired (CFH-Ab HUS) in cases with AB increase to factor H. AutoAb against factor H was determined by enzyme-linked immunosorbent assay (ELISA-VIDITEST anti-complement factor H). The search for mutations (n=167) was carried out using Next-generation Sequencing (NGS) and Sanger sequencing methods. Results: the sporadic form of aHUS was diagnosed in 96.9% of cases, familial in 3.1% and CFH-Ab HUS in 23.8%. The genetic nature of aHUS was confirmed in 53.4% of cases. Pathogenic mutations were detected in 8.6% of cases, probably pathogenic in 42.8% and those with unclear clinical significance in 46.8%. The complement genes mutations were detected in 88.5% of cases and mutations of genes not related to the complement system (ADAMTS13, DGKE, INF2) in 11.5%. The most frequently identified mutations were in the CFH (17.1%), C3 (12.9%) and CD46 (12.9%) genes and less frequently in CFI (7.1%), THBD (5.7%), CFHR5 (5.7%) and CFB (1.4%). In children with CFH-Ab HUS, the CFHR1/CFHR3 deletion was detected in 87.8% of cases, including in 19.4% in combination with mutations of unknown clinical significance. Multiple organ failure syndrome had developed in 77.8% of cases in children with pathogenic/probably pathogenic mutations, in 85.3% in patients with mutations of unknown clinical significance, in 91.8% in patients without mutations and in 83.3% in patients with CFHR1/CFHR3 deletion. Chronic kidney disease (CKD) stages 3 to 5 in sporadic/familial aHUS, regardless of genetic profile, had counted for 14.5% and 16.7% in CFH-Ab HUS. Lethal outcome occurred in 4.3% of cases in the presence of mutations, in 4.9% in the absence of mutations and in 2.8% in cases of CFHR1/CFHR3 deletion. Relapses of aHUS prior to the Eculizumab treatment had developed more often in the presence of CFHR1/CFHR3 mutations and deletion in comparison with children without mutations (31.4% v. 13.1%, p=0.0313 and 44.4% v. 13.1%, p= 0.004). Relapse of aHUS after discontinuation of the Eculizumab therapy had developed in 16.4% of cases. Risk factors for the relapse of aHUS were as follows: patient’s age above 12 months old at the time of the development of aHUS, severe arterial hypertension in the acute period, the use of Eculizumab at the fourth week after the onset of the disease and/or later, recurrent course of aHUS and the presence of CKD prior to the start of the Eculizumab therapy. Conclusion: The genetic profile of patients does not determine the severity and outcome of aHUS though it does affect the relapse rate. The prognosis and survival of patients with aHUS are determined by the severity of the acute period and the timeliness of the complement blocking therapy management.

Типичный гемолитико-уремический синдром (тГУС) – острое заболевание, вызываемое шига-токсин продуцирующими бактериями и характеризующееся развитием тромботической микроангиопатии. ТГУС является основной причиной острого повреждения почек у детей дошкольного возраста. Для тГУС характерен неблагоприятный прогноз при несвоевременной диагностике и лечении. Основой лечения является симптоматическая терапия с акцентом на заместительную почечную терапию. Цель исследования: Оценка лечения детей с типичным гемолитико-уремическим синдромом. Типичный гемолитико-уремический синдром у детей остается тяжелым, жизнеугрожающим заболеванием, требующим интенсивной терапии, включая заместительную почечную терапию. Анурия в дебюте заболевания является неблагоприятным фактором, ассоциированным с повышенным риском полиорганного поражения, вовлечения центральной нервной системы, летального исхода, а также длительной заместительной почечной терапии и неполного восстановления функций почек

Atypical hemolytic uremic syndrome (aHUS) is an orphan disease caused by hyperactivation of the alternative complement pathway. Objective of the study: to assess the state of the «ADAMTS13 – von Willebrand factor (vWF) – platelets» system in children with aHUS. Materials and methods of research: [by the FRET method (fluorescence resonance energy transfer) for the FRETSVWF73 (Peptide Institude, Inc., Japan)] hydrolysis of the fluorescent substrate and ADAMTS13 antigen [by ELISA using TECHNOZYM® ADAMTS13 5450551 ELISA (Technoclone GmbH, Austria)], vWF activity [for platelet agglutination (aggregation) in the presence of ristomycin (NPO Renam reagent kit for the ALAT-230LA-2 aggregometer, Russia)] and vWF antigen [by ELISA using the TECHNOZYM® vWF kit: Ag 5450201 ELISA (Technoclone GmbH , Austria)]. Results: there was a decrease in the activity and concentration of ADAMTS13 in 63% and 62% of patients, respectively. A decrease in vWF activity was noted in 44% of cases, an increase in its concentration – in 54% of children. Thrombocytopenia was diagnosed in 99% of children. Conclusion: the imbalance in the «ADAMTS13 – vWF – platelets» system supports the process of thrombus formation with the development of organ ischemia in aHUS under conditions of endothelial dysfunction. Reduced ADAMTS13 activity predicts the severity of the disease.

Atypical hemolytic-uremic syndrome (aHUS) is an extremely rare complement-mediated disease that belongs to the group of thrombotic microangiopathies (TMA). It often reoccurs after kidney transplantation (KT). Previously, KT was considered contraindicated in both children and adults with aHUS due to high (up to 50% and above) incidence of early graft loss associated with post-transplant recurrent TMA. Introduction of specific complement inhibitor therapy into clinical practice has improved outcomes in patients with aHUS and has significantly reduced the risk of post-transplant recurrence of underlying disease. We describe the clinical observation of a 20-year-old female patient with aHUS associated with antibodies to factor H, a major regulator of complement activation. The patient underwent KT and eculizumab was used for prophylactic purposes. In the postoperative period, the patient developed ureteral necrosis that required reconstructive surgery, followed by graft pyelonephritis. Despite postoperative complications, which were highly likely to trigger uncontrolled complement activation, TMA recurrence was avoided due to early treatment of the complications and prophylactic use of complement inhibitor therapy.

The article is devoted to an important issue of pediatric resuscitation such as acute kidney injury (AKI). A retrospective study of 245 patients with AKI was carried out. It was found out that the majority of patients were three years old. The causes of AKI were analyzed. In the entire group of patients the majority of causes were of renal nature. Meanwhile, the hemolytic-uremic syndrome (HUS) was the main cause of AKI in children. Children of different age had different causes and frequencies of AKI. The most serious population of patients suffered from AKI was represented by one-month-old babies.

Background: Data on etiology and clinical course of CKD stage 3 to 5 in children of preschool age could help obstetricians, pediatricians, and nephrologists with proper diagnostics and management of this condition and prediction of outcomes. Aim: To study causes and clinical features of CKD stage 3 to 5 in preschool children. Materials and methods: The causes and clinical features of CKD stage 3 to 5 were investigated in 55 preschool children aged from 7 months to 8 years. Twenty four had CKD stage 3 to 4 and 31 children with endstage CKD were on peritoneal dialysis. Results:96% of CKD stage 3 to 5 in preschool children were due to congenital/genetic kidney abnormalities. Predictors of renal replacement therapy beginning in the first 5 years of life were as follows: antenatal detection of congenital abnormalities of the kidney and urinary tract, oligohydroamnion, high neonatal BUN levels. Anemia, hyperparathyroidism, arterial hypertension were more prevalent in children on the dialysis stage of CKD, and myocardial hypertrophy and/or of the left ventricle dilatation were found in 26% of them. Forty two percent of children had growth retardation, and 40% had delayed speech development. Conclusion: The course CKD in preschool children is characterized by a combination of typical metabolic disorders with the growth retardation (often dramatic) and delayed mental development that significantly limits the possibilities of the social adaptation of these children and social activities of their parents. Participation of neuropsychiatrists, clinical psychologists, and teachers, rather than pediatricians and nephrologists only, is desirable in management of preschool children with CKD stage 3 to 5.

We analyzed 29 endosurgical pre-transplantation operations in children with thermal stage of chronic renal insufficiency. Their technical features are described in detail with the evaluation of intraand postoperative results and the time periods for the renewal ofperitoneal dialysis. It is shown that endosurgical nephrand nephrureterectomies provide an effective tool for pre-transplantation preparation of children with terminal stage of chronic renal insufficiency. Surgery using the retroperitoneoscopic approach allows to continue peritoneal dialysis within the first hours after surgery.

We analysed the results of pretransplant procedures in 29 children with end stage kidney disease. A detailed description of surgical technique was presented along with the evaluation of the intraoperative and postoperative outcomes of surgery. Renewal interval of peritoneal dialysis using was also discussed. High performance of endoscopic methods in children with end stage kidney disease was confirmed. Retroperitoneoscopic procedures enable doctors to continue using of peritoneal dialysis in the first hours after the surgery.