Epidemic hemolytic-uremic syndrome in children

Repetto, Horacio A.

doi:10.1038/ki.1997.508

Cited by 80 publications

(65 citation statements)

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“…The fact that C-9 prevents only 50% of rat mortality may be due to the inability of this compound to cross the blood brain barrier, so the rats could have died from neurological injuries. However, other causes observed in patients with HUS such as hyperkalemia, pulmonary edema, hypertension, and cardiac failure cannot be discarded (1).…”

Section: Discussionmentioning

confidence: 99%

“…The acute stage of the disease is marked by hypertension, edema, hematological abnormalities, and anuria (1,3). Clinical and histological renal damages have been strongly associated with Shiga toxin type 1 and/or 2 (Stx1, Stx2) produced by Escherichia coli O157:H7 and other related bacterial strains frequently isolated from children with HUS, although strains expressing Stx2 are highly prevalent in Argentina (4).…”

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A Glucosylceramide Synthase Inhibitor Protects Rats Against the Cytotoxic Effects of Shiga Toxin 2

et al. 2011

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Postdiarrhea hemolytic uremic syndrome is the most common cause of acute renal failure in children in Argentina. Renal damage has been strongly associated with Shiga toxin (Stx), which binds to the globotriaosylceramide (Gb3) receptor on the plasma membrane of target cells. The purpose of the study was to evaluate the in vivo effects of C-9, a potent inhibitor of glucosylceramide synthase and Gb3 synthesis, on kidney and colon in an experimental model of hemolytic uremic syndrome in rats. Rats were i.p. injected with supernatant from recombinant Escherichia coli expressing Stx2 (sStx2). A group of these rats were orally treated with C-9 during 6 d, from 2 d prior until 4 d after sStx2 injection. The injection of sStx2 caused renal damage as well as a loss of goblet cells in colonic mucosa. Oral treatment with C-9 significantly decreased rat mortality to 50% and reduced the extension of renal and intestinal injuries in the surviving rats. The C-9 also decreased Gb3 and glucosylceramide expression levels in rat kidneys. It is particularly interesting that an improvement was seen when C-9 was administered 2 d before challenge, which makes it potentially useful for prophylaxis. (Pediatr Res 69: 390-394, 2011)

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Section: Discussionmentioning

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A Glucosylceramide Synthase Inhibitor Protects Rats Against the Cytotoxic Effects of Shiga Toxin 2

et al. 2011

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“…HUS constitutes the most common cause of ARF in Argentina. Approximately 2–4% of patients die during the acute phase, and one third out of the 96% who survive are at risk of having chronic renal sequelae [1]. However, the pathophysiology of ARF during HUS is not well understood.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Stx2 Tubular Response in a Rat Experimental Model of Hemolytic Uremic Syndrome

Ochoa¹,

Lago

Gerhardt³

et al. 2010

Am J Nephrol

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Background/Aims: In Argentina, hemolytic uremic syndrome (HUS) constitutes the most frequent cause of acute renal failure in children. The aim of our study was to analyze the early tubular response under the effect of Shiga toxin type 2 (Stx2) in a rat experimental model of HUS. Methods: Adult male Sprague-Dawley rats were injected intraperitoneally with culture supernatant from recombinant Escherichia coli expressing Stx2. Functional, histological, immunohistochemical and Western blot studies were performed at 48 h postinoculation. Results: Renal tubules showed the loss of the epithelial markers E-cadherin and β-catenin, and an increase in transforming growth factor-β1 expression. We detected the expression of α-smooth muscle actin in the interstitium and fibrosis in the periglomerular areas. Conclusion: Our results indicate that the early tubular response to the effects of Stx2 is related to an immunophenotype change of tubular cells and the presence of mild fibrosis in the interstitium.

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“…HUS develops in 5 to 10% of children several days after bloody diarrhea and is a systemic disease characterized by thrombotic microangiopathy, hemolytic anemia, thrombocytopenia, and acute renal failure. HUS is the most common cause of acute renal failure in children and the second leading cause of chronic renal failure in children younger than 5 years old (3,4). STEC O157:H7 is by far the most prevalent serotype associated with HUS although non-O157 STEC strains have been also isolated from children with HUS (5,6).…”

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Inhibition of Water Absorption and Selective Damage to Human Colonic Mucosa Are Induced by Subtilase Cytotoxin Produced by Escherichia coli O113:H21

et al. 2013

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b Shiga toxin-producing Escherichia coli O157:H7 (STEC) is by far the most prevalent serotype associated with hemolytic uremic syndrome (HUS) although many non-O157 STEC strains have been also isolated from patients with HUS. The main virulence factor of STEC is the Shiga toxin type 2 (Stx2) present in O157 and non-O157 strains. Recently, another toxin, named subtilase cytotoxin (SubAB), has been isolated from several non-O157 strains and may contribute to the pathogenesis of HUS. Here, we have demonstrated that an O113:H21 STEC strain expressing SubAB and Stx2 inhibits normal water absorption across human colon and causes damage to the surface epithelium, necrosis, mononuclear inflammatory infiltration, edema, and marked mucin depletion. This damage was less marked, but nevertheless significant, when purified SubAB or E. coli O113:H21 expressing only SubAB was assayed. This is the first study showing that SubAB may directly participate in the mechanisms of diarrhea in children infected with non-O157 STEC strains. Shiga toxin-producing Escherichia coli (STEC) strains colonize the human colon and may cause systemic complications such as hemolytic uremic syndrome (HUS) (1, 2). HUS develops in 5 to 10% of children several days after bloody diarrhea and is a systemic disease characterized by thrombotic microangiopathy, hemolytic anemia, thrombocytopenia, and acute renal failure. HUS is the most common cause of acute renal failure in children and the second leading cause of chronic renal failure in children younger than 5 years old (3, 4). STEC O157:H7 is by far the most prevalent serotype associated with HUS although non-O157 STEC strains have been also isolated from children with HUS (5, 6). The main virulence factor of STEC is the Shiga toxin type 2 (Stx2) present in O157 and non-O157 strains (7,8). Unlike O157:H7 strains, some non-O157 STEC strains, among them O113:H21, lack the locus of enterocyte effacement (LEE) but encode additional proteins in order to adhere to intestinal epithelial cells (9). Recently, it has been reported that certain LEE-negative STEC strains produce another cytotoxin, named subtilase cytotoxin (SubAB), which may contribute to the pathogenesis of HUS. SubAB is toxic for eukaryotic cells, and its mechanism of action involves highly specific A-subunit-mediated proteolytic cleavage of the essential endoplasmic reticulum chaperone BiP (10, 11). To date, the in vivo effects of SubAB have only been examined in mice. Gut colonization with recombinant E. coli expressing subAB genes did not cause diarrhea but produced a dramatic weight loss over a 6-day period (11). Interestingly, intraperitoneal injection of purified SubAB caused microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment, characteristics typical of Stxinduced HUS (12). These findings raise the possibility that SubAB directly contributes to pathology in humans infected with STEC strains that produce both Stx and SubAB.The purpose of the present study was to examine the physiological and morphological effects of STE...

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Epidemic hemolytic-uremic syndrome in children

Cited by 80 publications

References 80 publications

A Glucosylceramide Synthase Inhibitor Protects Rats Against the Cytotoxic Effects of Shiga Toxin 2

A Glucosylceramide Synthase Inhibitor Protects Rats Against the Cytotoxic Effects of Shiga Toxin 2

Characterization of Stx2 Tubular Response in a Rat Experimental Model of Hemolytic Uremic Syndrome

Inhibition of Water Absorption and Selective Damage to Human Colonic Mucosa Are Induced by Subtilase Cytotoxin Produced by Escherichia coli O113:H21

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