Hemolytic-uremic syndrome (HUS) consists of microangiopathic hemolytic anemia, thrombocytopenia and acute, potentially fatal, kidney failure. As the name suggests, this is a syndrome and not a disease, meaning that its etiology is diverse, and causes of HUS can include postmedication reactions, pregnancy, antiphospholipid syndrome, systemic lupus erythematosus, genetic factors such as complement genes mutation, antibodies to complement factor H, or infection with HIV or bacteria such as Escherichia coli, Shigella dysenteriae or Streptococcus pneumoniae. In an important number of cases, however, particular strains of E. coli appear to be the causative agents of HUS, especially in children. HUS develops in association or not with a previous bloody diarrhea syndrome. Enterohemorrhagic E. coli (EHEC) has the capacity to induce lesions in human enterocytes through mechanisms of attachment/effacement (A/E) and through synthesis of Shiga-like toxins 1 and 2. The A/E genes are located in a pathogenic chromosomal island called LEE (locus of enterocyte effacement), which codes for secretory proteins and systems, as well as  intimin and its translocated receptor, Tir. Intimin is expressed on the outer membrane of E. coli and plays a major role in attachment to human enterocytes, through its specific interaction with Tir, a receptor synthetized by E. coli and translocated by the bacteria directly into host membrane cells.1,2 E. coli O157:H7 is considered to be the main E. coli serotype involved in HUS; it
associates destruction of apical microvilli of the intestinal epithelial cells, skeleton rearrangements, and tight attachment of bacteria to enterocytes, followed by invasion and disease. Other serotypes of E. coli that have been linked to HUS have been reported to be O111:H8, O103:H2, O121, O145, O26, O113, O104:H4.4.3 Apart from the A/E mechanisms, the production of bacteriophage-coded Shigalike toxins (Stx) by specific EHEC strains (STEC) may also be involved in the pathogenesis of HUS, although HUS can be classified into two main categories, with present or absent Stx.3 Stx-1 and Stx-2 bind to different epitopes on the target cells; because Stx-2 has a slower dissociation rate from the target cell, it may cause more severe disease than Stx-1.3 Apart from A/E coded in the LEE island and Shiga-like toxin production coded by Stx, additional virulence factors may contribute to the pathogenesis of E. coli infection.4 HUS may associate elements from the following clinical picture: bloody diarrhea, vomiting, abdominal cramps, fever, facial pallor, accompanied by signs of renal insufficiency such as pollakiuria, hematuria and edema, signs of thrombocytopenia such as bruising or bleeding, or signs of neurologic damage due to uremia translated through fatigue, confusion, obtundation or seizures.

Acute kidney injury occurs in as many as 70% of the patients,3 and may associate a potentially fatal acute evolution. However,
after recovery from HUS, renal function returns to normal in up to 85% of cases,3 although a certain degree of permanent subclinical nephron loss has been described, leading to small reductions in the glomerular filtration rate.5 The mechanisms of acute renal injury are diverse, and may include direct bacterial pathogenesis, through hematogenous polymorphonuclear cellassociated6 transmigration of Stx from the colon to the kidney, where it induces endothelial damage, direct toxicity and
inflammation through the stimulation of local production of cytokines and, specifically, chemokines leading to increased local leukocyte recruitment with occlusion of the microvascular space.4,7 Other mechanisms include thrombotic microangiopathy of the arterioles and capillaries, as well as red blood cell fragmentation with hemolytic anemia.3 Sources of E. coli may include food products such as undercooked beef meat, raw milk or cheese,8 raw juice, fresh fruits and vegetables, particularly sprouts,spinach, or lettuce, which are hard to clean properly prior to eating. Other sources include contaminated water, contact with animals (particularly cows, sheep and goats) or their environment, and person-to-person transmission through fecal-oral route. Infection with E. coli can be prevented through thorough hygienic practices, such as washing hands before and after cooking or eating food, before and after using the toilet, before and after contact with animals or their environment; washing, peeling and re-washing fruits and vegetables; pasteurizing or boiling milk; boiling or deepcooking meat; avoiding contact of raw meat (as well as used plates and utensils that came in contact with raw meat during preparation) with vegetables or fruits that will be consumed raw, etc. 9 Treatment of HUS mainly relies on supportive therapy. Plasma exchange/plasmapheresis and eculizumab appear to be the only specific therapies approved for HUS. Administration of antibiotics for EHEC dysentery has been shown to increase the risk for HUS, and is therefore not indicated when E. coli has been identified as the etiologic agent. Supportive treatment of HUS includes transfusion of packed red blood cells for severe anemia, management of bleeding due to severe thrombocytopenia, fluid and electrolyte balance, renal replacement therapy in severe cases of acute kidney injury meeting the criteria for dialysis, management of hypertension, control of seizures or other neurologic manifestations. In conclusion, HUS is a complex syndrome generally but not always linked to an infectious etiology, which requires close monitoring and effective management by interdisciplinary teams, particularly for pediatric cases. 

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