According to statistics, the prevalence of atypical hemolytic uremic syndrome (aHUS) is about seven in one million. The majority of aHUS have complement-related factor gene mutations, and the etiology of about 6% to 10% of patients with atypical hemolytic uremic syndrome is related to antibodies to complement proteins.
Patients may have both antibodies to complement proteins and genetic mutations. About 20% to 30% of patients have a family history of atypical hemolytic uremic syndrome, and about 60% of patients will develop the disease in adulthood. In 70%-80% of patients, there is an incentive to activate the alternative pathway of complement.
Symptoms of Atypical Hemolytic Uremic Syndrome
(1) Microangiopathic hemolytic anemia
(2) Acute renal impairment
Methods for Examination of Atypical Hemolytic Uremic Syndrome
(1) Evaluation of Complement Factors and Autoantibodies
This examination includes the determination of complement C3 and C4, which can detect a decrease in complement C3 and an occasional decrease in complement C4. Impairment of function is often caused by missense mutations in complement proteins, but complement protein levels are not affected. Therefore, even if the plasma C3, C4, CFI, CFB, and CFH levels are normal, the diagnosis of complement-mediated HUS cannot be completely ruled out.
(2) Microangiopathic Hemolytic Anemia
It often manifests as anemia, thrombocytopenia, broken red blood cells seen on the blood smear, and a negative Coombs test result.
(3) Complement Gene Screening
Screening of patients mainly includes the following points: positive family history, previous experience of HUS attack, poor clinical course, onset within 6 to 12 months after birth, onset during childbirth or postpartum, and unknown etiology. Screening for complement genes should be considered, including C3, MCP (CD46), CFH, CFHR5, etc.
(4) Acute Kidney Injury
Patients should accept acute kidney injury examination, the severity of which ranges from hematuria and proteinuria to severe renal failure. Urinalysis in most patients would show abnormal red blood cell morphology and occasionally red blood cell casts.
(5) Pathological Diagnosis
The main organ involved in atypical hemolytic uremic syndrome is the kidney. Pathological changes in the kidney can generally manifest as thrombotic microangiopathy, involving renal arterioles, glomeruli, and renal interstitium. This disease divides the pathological manifestations of HUS into three types:
(a) Glomerular disease
(b) Renal cortical necrosis type
(c) Arterial disease
Treatment of Atypical Hemolytic Uremic Syndrome
(1) Plasma Replacement Therapy
This approach is the first-line treatment for atypical hemolytic-uremic syndrome. It can remove defective mutant complement proteins and autoantibodies in patients, while supplementing normal complement proteins and reducing the risk of hypertension in patients with acute kidney injury.
(2) Block the Complement Activation Pathway
Blocking the cleavage of the humanized C5 monoclonal antibody can in turn block the production of the membrane attack complex C5b-9 and the terminal complement component C5a, reducing thrombosis, endothelial damage, and subsequent renal damage.
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