Overview of the regional experience in the diagnostics and treatment of atypical-hemolytic uremic syndrome in the Chelyabinsk Oblast of Russia

Abstract

Atypical hemolytic-uremic syndrome (aHUS) is a rare systemic life-threatening disorder with an unfavorable prognosis and progressive course and is based on chronic uncontrolled overactivation of the alternative complement pathway of hereditary (gene mutations with loss of function of complement regulators/activators) or acquired nature (antibodies to factor H), which leads to the development of a systemic complement-mediated form of thrombotic microangiopathy (TMA). The pathomorphological essence of TMA is the development of endotheliosis, which in its turn triggers the activation of the coagulation cascade with the formation of platelet-fibrin thrombi, partially or completely occluding the lumen of the vessels of the microvasculature (small arteries and arterioles). The therapeutic approach to aHUS has been improved with the introduction of eculizumab, a humanized monoclonal antibody, into clinical practice. Eculizumab has a high affinity for the C5 component of complement and, by binding to it, completely blocks the splitting of C5 into C5a and C5b. As a result, the formation of pro-inflammatory cytokines is inhibited by blocking the formation of C5a and the membrane attack complex (MAC) by blocking the formation of C5b. This therapy improves the prognosis of the disease and reduces the risk for development of the life-threatening conditions, including end-stage chronic kidney disease (CKD). The Article represents the analysis of the Authors’ own clinical experience with aHUS in the region of the Chelyabinsk Oblast of Russia. The diagnosis of aHUS was based on a combination of microangiopathic non-immune hemolytic anemia, thrombocytopenia, and acute kidney injury, after excluding other forms of TMA. Most often, aHUS in the form of clinical manifestations of TMA was diagnosed in pediatric patients during the first 3 years of life (67%). Both pathogenic and possibly-pathogenic mutations associated with the development of aHUS were detected in 56% of cases. These included mutations in the CFH, CFI, C3 genes, heterozygous deletion of CFHR1/CFHR3. Eculizumab had demonstrated its high efficiency accompanied by the restoration of diuresis, a decrease in the severity of arterial hypertension, a rapid suppression of hemolysis activity and the signs of active TMA. Throughout the course of treatment, all patients maintained hematological remission coupled with the absence of necessity for continuing extracorporeal therapy. Conclusion: the onset of remission of aHUS against the background of complement blocking therapy with eculizumab confirmed the correctness of the established diagnosis and the chosen treatment tactics.