Clinical Pearls & Morning Reports
Published June 20, 2018
A laboratory finding that is commonly seen in cases of atypical hemolytic–uremic syndrome is low activity in the alternative complement pathway, according to the AH50 assay, which indicates either a deficiency of an alternative or terminal complement pathway component or complement consumption. Read the latest Case Records of the Massachusetts General Hospital here.
Q: What is the most common cause of acute kidney injury in community-based pediatric practices?
A: In community-based pediatric practices, cases of acute kidney injury are most commonly caused by prerenal conditions, in which decreased renal perfusion leads to a decreased glomerular filtration rate. In prerenal diseases, renal tubular function remains intact and there is avid resorption of sodium and water in response to the hypoperfusion; as a result, oliguria develops. The most common prerenal cause of acute kidney injury is volume depletion, which can be due to blood loss or excessive loss of water from the gastrointestinal tract, the skin, or the urinary tract. Patients with a prerenal cause of acute kidney injury should have improvement in response to volume expansion, which restores renal perfusion.
Q: What diagnoses may cause an illness with acute kidney injury, hemolytic anemia, consumptive thrombocytopenia, and infectious bloody diarrhea?
A: The list of diagnoses that could be associated with all four of these processes includes disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, systemic vasculitis, and the hemolytic–uremic syndrome.
A: Hemolytic–uremic syndrome is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Most cases of the hemolytic–uremic syndrome occur after infection (classically infection with Shiga toxin–producing Escherichia coli ); on rare occasions, the syndrome can occur as a complication of invasive infection with Streptococcus pneumoniae. Other cases of the hemolytic–uremic syndrome are classified as atypical; these are mainly primary disorders of complement regulation that can be either sporadic or familial. While a history of bloody diarrhea might suggest a diagnosis of the hemolytic–uremic syndrome due to Shiga toxin–producing E. coli, cases of atypical hemolytic–uremic syndrome can also be preceded by a triggering event, such as diarrhea.
A: Atypical hemolytic–uremic syndrome is a clinical diagnosis that is supported by laboratory test results, and it should be considered when other causes of thrombotic microangiopathy have been ruled out. A variety of mutations in complement component genes have been described in patients with atypical hemolytic–uremic syndrome. Known pathogenic variants are in the C3, C4BPA, C4BPB, MCP, CFB, CFH, CFHR1, CFHR3, CFHR4, CFHR5, CFI, DGKE, and THBD genes; most of these genes encode alternative complement pathway components or inhibitors. Variants in these genes are identified in approximately 70% of patients with atypical hemolytic–uremic syndrome. Among patients with atypical hemolytic–uremic syndrome, the prognosis is worse in those who have CFH mutations than in those who have MCP mutations or in those in whom the causative mutations are unknown.