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Hemolytic-uremic-syndrome (HUS)  
Hemolytic uremic syndrome (HUS) is characterized by

Diarrhea and upper respiratory infection are the most common precipitating factors. HUS is one of the most common causes of acute renal failure in children.

HUS occurs primarily in infants & small children & pregnant or postpartum women, occasionally in older children & nonpregnant adults.

In children, HUS often follows a prodromal infectious disease, usually diarrhea (90%), less often an upper respiratory infection (10%). Use of antimotility drugs may increase the risk of developing HUS. The most commonly associated diarrheal illnesses include those due to the pathogens Escherichia coli serotype 0157:H7 and Shigella, Salmonella, Yersinia, and Campylobacter species. The Shiga and Shigalike toxins, produced by some strains of Shigella dysenteriae and E coli 0157:H7, respectively, have been associated with approximately 70% of cases of HUS in children. Implicated viruses include varicella, echovirus, and coxsackie A and B.

HUS also is associated with other infections, cancer, and the administration of chemotherapeutic agents. Some have suggested that HUS is mediated by immune complexes. Some cases of HUS are familial, which may reflect a genetic or human leukocyte antigen (HLA)-type predisposition.

HUS and thrombotic thrombocytopenic purpura (TTP) represent different ends of what is probably the same disease continuum. Both involve microvascular lesions with platelet-fibrin hyaline microthrombi that occlude arterioles and capillaries. The platelet aggregation results in a consumptive thrombocytopenia. A defect in the vascular epithelium is thought to cause the platelet aggregation. The epithelial damage may result from toxins released by bacteria or viruses. In TTP, the hyaline microthrombi occur throughout the microcirculation; in HUS, they essentially are confined to the kidneys.

While the vascular lesions are identical in HUS and TTP, involvement of the CNS predominates in TTP. Renal involvement is the defining feature of HUS. In both, the platelet and fibrin microthrombi within the renal microvasculature are accompanied by thrombocytopenia and a microangiopathic hemolytic anemia.

Differential Diagnosis:

No effective therapy exists for HUS. Management consists of early dialysis for acute renal failure and general supportive care, including treatment of hypertension.  Plasmapheresis & plasma exchange has been tried without clear evidence of its efficacy.

Therapy for The Hemolytic–Uremic Syndrome    NEJM August 22, 2002 - Joel L. Moake

In mildly affected children with the hemolytic–uremic syndrome who have had oligoanuria for less than 24 hours, appropriate management of fluid and electrolyte levels is usually sufficient. Otherwise, the duration of anuria and attendant dialysis support correlates inversely with the likelihood of full recovery. Acute renal failure is often more severe in adults. Ultimately, care for end-stage renal disease may be required.

Plasma infusion or exchange has been tried, with equivocal results.  

Even the infusion of normal fresh-frozen plasma (containing factor H) in patients with familial hemolytic–uremic syndrome has not succeeded in preventing relapses or progressive renal disease.  

Purified or recombinant factor H may eventually be developed for use in patients with a deficiency of factor H.  Plasma adsorption over staphylococcal protein A columns has been reported to be useful in cases of thrombotic microangiopathy due to mitomycin.

Antimotility agents increase the risk of the hemolytic–uremic syndrome after infection with E. coli O157:H7.

Antimicrobial agents increase the release of Shiga toxin from E. coli O157:H7, and antibiotic therapy may thus paradoxically increase the risk of the hemolytic–uremic syndrome in infected children.  Normal persons generate neutralizing antibodies against Shiga toxin in response to infection with toxin-producing microbes, and the intranasal immunization of mice with the B subunit of E. coli Shiga toxin 1 elicits antibodies that neutralize the exotoxin.  These observations hold promise for the development of a vaccine against E. coli O157:H7.  It is not known whether anticoagulant therapy is useful or safe.

Mortality rate is 5-15%.  Approximately 85% of children recover if given supportive care.
With conservative management including dialysis, most infants & children with HUS will recover.
The prognosis for recovery in adults is less certain. Postpartum women often do not recover renal function .

Arch IM 10-23-95;155:2077 Review
E-Medicine   Hemolytic-Uremic Syndrome  June 15 2001, Volume 2, Number 6  
NEJM August 22, 2002 - Joel L. Moake   Review of Thrombotic Microangiopathies

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