ABSTRACT
Atypical hemolytic uremic syndrome (aHUS), a rare variant of thrombotic microangiopathy, is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. The condition is associated with poor clinical outcomes with high morbidity and mortality. Atypical HUS predominantly affects the kidneys but has the potential to cause multi-organ system dysfunction. This uncommon disorder is caused by a genetic abnormality in the complement alternative pathway resulting in over-activation of the complement system and formation of microvascular thrombi. Abnormalities of the complement pathway may be in the form of mutations in key complement genes or autoantibodies against specific complement factors. We discuss the pathophysiology, clinical manifestations, diagnosis, complications, and management of aHUS. We also review the efficacy and safety of the novel therapeutic agent, eculizumab, in aHUS, pregnancy-associated aHUS, and aHUS in renal transplant patients.
Subject(s)
Antibodies, Monoclonal, Humanized/pharmacology , Atypical Hemolytic Uremic Syndrome , Complement Pathway, Alternative , Atypical Hemolytic Uremic Syndrome/diagnosis , Atypical Hemolytic Uremic Syndrome/etiology , Atypical Hemolytic Uremic Syndrome/physiopathology , Atypical Hemolytic Uremic Syndrome/therapy , Complement Pathway, Alternative/drug effects , Complement Pathway, Alternative/genetics , Complement Pathway, Alternative/immunology , Disease Management , Humans , Immunologic Factors/pharmacologyABSTRACT
BACKGROUND: Impaired renal function has been shown in previous studies to be an independent predictor of cardiovascular adverse events amongst patients admitted for percutaneous coronary intervention (PCI) following ST-segment elevation myocardial infarction (STEMI). This study investigates the impact of admission serum creatinine (SCr) on major cardiovascular outcomes among STEMI patients undergoing PCI. METHODS: A retrospective study of patients admitted for PCI following STEMI was conducted using the National Cardiovascular Database Action Registry (NCDR) at Cleveland Clinic Akron General (CCAG) Hospital. The primary outcome was a composite of major clinical events: cardiogenic shock, atrial fibrillation, ventricular tachycardia/fibrillation, heart failure, bleeding and mechanical ventilation. SCr was an independent and continuous variable. RESULTS: A total of 656 patients included in the study with the diagnosis of STEMI who subsequently underwent primary PCI. Patients with eGFR < 60 mL/min/1.73 m2 on admission had an increased incidence of cardiogenic shock (P = 0.001), bleeding (P < 0.001), heart failure (P < 0.0005) and higher mortality rates (P = 0.0005). Furthermore, in the setting of STEMI, elevated SCr was also associated with an increased risk of developing major adverse events like cardiogenic shock (P = 0.05), bleeding (P = 0.05), and heart failure (P = 0.005). CONCLUSIONS: In the setting of STEMI, elevated SCr and eGFR < 60 mL/min/1.73 m2 was associated with an increased risk of developing major adverse events including cardiogenic shock, bleeding and heart failure.