07/01/2015
Hemolytic-Uremic Syndrome
The hemolytic-uremic syndrome (HUS) is the most common cause of acute renal failure in young children and is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and uremia. HUS has features common to thrombotic thrombocytopenic purpura, except that the latter tends to occur in young adult women as a relapsing illness with fever, serious central nervous system involvement, and thrombocytopenia.
Etiology.
An acute enteritis with diarrhea caused by Shiga toxin-producing Escherichia coli 0157:H7 precedes 80% or more of HUS cases in developed countries. The reservoir of this organism is the intestinal tract of domestic animals. It is usually transmitted by undercooked meat and unpasteurized milk. Outbreaks have followed ingestion of contaminated apple cider or bathing in a contaminated swimming pool. The organism elaborates a toxin, verotoxin, which is absorbed from the intestines and initiates endothelial cell injury. Less often, HUS is associated with other bacterial (Shigella, Salmonella, Campylobacter, Streptococcus pneumoniae, Bartonella) and viral (coxsackievirus, echovirus, influenza, varicella, HIV, Epstein-Barr) infections. HUS may also develop with the use of oral contraceptives, mitomycin, cyclosporine, and pyran copolymer, which is an inducer of interferon. In addition, a hemolytic-uremic type of disorder has been reported with systemic lupus erythematosus, malignant hypertension, preeclampsia, postpartum renal failure, and radiation nephritis. Several reports describe occurrence in more than one member of a family, but the role of genetic factors in predisposition to the disease is unknown.
Pathogenesis.
The primary event in pathogenesis of the syndrome appears to be endothelial cell injury. Capillary and arteriolar endothelial injury in the kidney leads to localized clotting. Evidence for disseminated intravascular coagulation is unusual. The microangiopathic anemia results from mechanical damage to the red blood cells (RBCs) as they pass through the altered vasculature. Thrombocytopenia is caused by intrarenal platelet adhesion or damage. Damaged RBCs and platelets are removed from circulation by the liver and spleen. Nondiarrheal and sporadic familial cases of HUS may be caused by the absence of a plasma factor that stimulates the production of endothelial cell-derived prostacyclin, which promotes vasodilatation and inhibits thrombosis. Reduced levels of thrombomodulin, tissue plasminogen activator, and heparin-like molecules, which activate antithrombin III, result in a prothrombotic state in HUS. In addition, serum levels of prothrombotic agents, including platelet- activating factor, prothrombin fragment 1 and 2, tissue plasminogen activator antigen, tissue plasminogen activator-inhibitor (TPA-1) complex, von Willebrand factor, d-dimer, and thromboxane A2 are increased before renal injury occurs and may be a cause of injury.
Clinical Manifestations.
HUS is most common in children younger than age 4 yr. The onset is usually preceded by a gastroenteritis characterized by fever, vomiting, abdominal pain, and diarrhea that is often bloody. Less commonly, patients may present after an upper respiratory tract infection. Sudden onset of pallor, irritability, weakness, lethargy, and oliguria usually occurs 5-10 days after the initial gastrointestinal or respiratory illness. Physical examination may reveal dehydration, edema, petechiae, hepatosplenomegaly, and marked irritability.
