P0082CHARACTERISTICS OF ADULT PATIENTS WITH ATYPICAL HEMOLYTIC UREMIC SYNDROME IN RUSSIA
Authors: Demyanova Kseniya , Kozlovskaya Natalia , Korotchaeva Yuia 
Published: June 2020

Background and Aims

Atypical hemolytic uremic syndrome (aHUS) is complement mediated thrombotic microangiopathy (TMA), caused by genetic abnormalities in the complement gene cluster. Information about the course of aHUS in the adult population in Russia is not enough accumulated. This study presents the characteristics of Russian adult patients (pts) with aHUS.

Aim

To assess the characteristics of adult pts with aHUS in Russia.

Method

statistical analysis of retrospective and prospective data

The study included 243 pts with acute TMA (microangiopathic hemolytic anemia, thrombocytopenia, decreased haptoglobin and / or blood schizocytosis, kidney damage) from different regions of Russia. All patients were tested for ADAMTS-13 activity, and there were no accidents of TTP in our study. Cases of acute TMA associated with pregnancy and childbirth (n=134), systemic diseases (n=10), anticancer drugs treatment (n=1) and sepsis (n=13) were excluded. 85 pts with diagnosis of aHUS were selected for further analysis.

Results

Characteristics of pts are presented in table 1. The average age at the time of acute episode was 32.4 years, the disease was equally common among men and women. Relapsing course was rare (n=11, 13%), the maximum number of relapses – 5. In the debut, 67.8% of pts had signs of kidney damage, in 21% - gastrointestinal tract, 4.8% - CNS, 4.8% - pulmonary thromboembolism, 1.6% - visual impairment. During the acute episode, extrarenal manifestations were detected in 70% of pts, while in 38 cases (44.7%), multiple organ failure (MOF) developed with simultaneous damage from 3 to 7 organs. The most commonly observed symptoms of gastrointestinal lesions (n = 39, 45%), CNS (n = 32, 37%), heart (n = 18, 21%), less often - the organ of vision (n = 10, 12%). Kidney damage was characterized by the development of AKI in 70%, in the rest - urinary syndrome, arterial hypertension, the initial signs of renal dysfunction in various combinations. A morphological examination of kidney was performed in 40 pts (kidney biopsy - 35, autopsy - 5): acute TMA was detected in 28 pts (70%), chronic TMA - in 7 (17.5%), a combination of acute and chronic TMA - in 2 (5%), a combination of IgA-nephropathy and TMA - in 1 case (2.5%) and in 2 patients a membrane-proliferative glomerulonephritis pattern with TMA. Genetic analysis was performed in 19 pts (22%), in 7 of which (37%) identified gene variants associated with the development of aHUS (C3 in 3 pts, CFHR5 in 2 pts, CFH in 2, in 1 case - MCP and in 1-DGKE). In addition, variants of genes of the complement system with an unclear clinical value were found in all pts (n = 19). 72% of pts (n = 61) needed renal replacement therapy, almost all pts received plasma therapy (83%) and anticoagulants (85%). Only 13 pts (15%) received complement-blocking therapy with eculizumab. In the outcome of the acute episode in 12 cases (14%) renal function fully recovered, in 20 pts (23%) signs of renal dysfunction persisted (CKD 2–4 stages), 53 pts (62.3%) reached ESRD, 10 pts died (12%).

Conclusion

The features of aHUS in our cohort were:

1. Severe course with the development of MOF in 45% of cases

2. High frequency of ESRD in the outcome of aHUS (62.3%)

3. The incidence of genetic mutations (37%) is comparable to foreign cohorts