[Diagnosis, treatment, and genetic analysis of five cases of primary atypical hemolytic uremic syndrome].

A retrospective analysis was conducted on the clinical characteristics, renal pathology, genetic testing, and treatment of five patients -two males and three females-diagnosed with primary atypical hemolytic uremic syndrome (aHUS) in the Department of Nephrology at the Affiliated Hospital of Qingdao University from February 2022 to June 2024. The patients' ages at disease onset ranged from 14 to 29 years. Four patients experienced prodromal infection symptoms. At disease onset, serum creatinine levels ranged from 168.5 to 1 230.2 μmol/L. All patients presented with hematuria, proteinuria, hypertension, non-immune hemolytic anemia, thrombocytopenia, elevated lactate dehydrogenase (LDH), and fragmented red blood cells in peripheral blood (0.5%-6.0%). Serum haptoglobin levels were below the normal lower limit in all cases. Four patients demonstrated decreased serum complement C3, while one maintained normal serum complement C3 throughout the course of the disease. One patient exhibited serum factor H concentrations below the normal lower limit. Another patient tested positive for anti-factor H antibodies. Renal biopsies were performed on four patients. Electron microscopy revealed typical acute-phase pathological features of aHUS in three cases, including glomerular endothelial cell swelling and widened subendothelial spaces. One patient demonstrated ischemic and atrophic changes in the glomerular capillaries, while another had concurrent membranous nephropathy. Whole-exome high-throughput sequencing related to aHUS was performed in all five patients, revealing heterozygous gene mutations in each case. Complement-related gene mutations, typically occurring in a heterozygous state, are prevalent in aHUS patients. The eight heterozygous gene variations identified in this study were absent from existing databases of known aHUS-associated pathogenic mutations. Four patients received eculizumab treatment at varying time points following diagnosis, resulting in differing clinical outcomes. The patient positive for anti-factor H antibodies was treated with rituximab. The patient with membranous nephropathy initiated combination therapy with rituximab and eculizumab after six months of eculizumab monotherapy. Following treatment, all five patients achieved complete cessation of intravascular mechanical hemolysis, with normalization of LDH and platelet levels, as well as varying degrees of renal function recovery. From a pathophysiological perspective, the timely administration of the complement C5 inhibitor eculizumab can rapidly induce clinical remission, reduce the incidence of end-stage renal disease, and improve prognosis in patients with aHUS.