The hemolytic-uremic syndrome

doi:10.1016/S0022-3476(64)80337-1

The Journal of Pediatrics

Volume 64, Issue 4, April 1964, Pages 478-491

https://doi.org/10.1016/S0022-3476(64)80337-1 Get rights and content

The combination of acute renal failure, thrombocytopenia, and hemolytic anemia associated with distorted erythrocytes (“burr” cells) constitutes the hemolytic-uremic syndrome. These observations of the natural history of 58 affected infants and children represent the largest single group studied. Preliminary serologic studies point to a viral etiology in some cases. During the acute phase, the mortality rate has been lowered substantially by the judicious use of transfusions of packed erythrocytes and improvements in the treatment of the acute, renal failure. The severity of renal failure and central nervous system abnormalities appear to influence the frequency of sequelae. It is not clear whether affected children represent the clinical expressions of one disease or reflect similar changes induced by diverse disease processes.

References (31)

GianantonioC.A. et al.
Acute renal failure in infancy and childhood
J. Pediat.
(1962)
GajdusekD.C.
Virus hemorrhagic fever
J. Pediat.
(1962)
MacWhinneyJ.B. et al.
Thrombotic thrombocytopenic purpura in childhood
Blood
(1962)
ShumwayC.N. et al.
An unusual syndrome of hemolytic anemia, thrombocytopenic purpura, and renal disease
Blood
(1957)
GasserC. et al.
Hamolytisch-uramische Syndrome: bilaterale Nierenrindennekrosen bei Akuten erworbenen hamolytischen Anamien
Schweiz. med. Wchnschr.
(1955)
RoyerP. et al.
La Micro-angiophatie Trombotique du rein chez l'enfant
Semaine hop. Paris
(1960)
JavettS.N. et al.
Syndrome of hemolysis thrombopenia and nephropathy in infancy
Pediatrics
(1962)
LamvikJ.
Acute glomerulonephritis with hemolytic anemia in infants. Report of three fatal cases
Pediatrics
(1962)
AllisonA.C.
Acute haemolytic anaemia with distortion and fragmentation of erythrocytes in children
Brit. J. Haemat.
(1957)
GriffithsJ. et al.
Haemolytic uraemic syndrome in infants
Arch. Dis. Childhood
(1961)

RosenthalD.

The syndrome of hemolytic anemia thrombocytopenia and uremia

A. M. A. J. Dis. Child.

(1962)

VildosolaJ. et al.

Sindrome hemolitico-uremico en la infancia

Pediatria

(1962)

Fleisher, D. S., McElfresh, A. E., and Arey, J. B.: Personal...

ZingaleS.B. et al.

Empleo del gel de poliacrilamide en la electroforesis de las proteinas sericas. I. Metodo

Medicina

(1961)

MettlerN.E. et al.

Aislamiento del agente causal del Sindrome uremico-hemolitico

Medicina

(1963)

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Shiga toxin-producing Escherichia coli is the main cause of post-diarrheal hemolytic uremic syndrome (HUS) which produces acute kidney injury mainly in children, although it can also affect adults. The kidneys are the organs most affected by Shiga toxin type 2 (Stx2) in patients with HUS. However, previous studies in pregnant rats showed that a sublethal dose of Stx2 causes severe damage in the uteroplacental unit and induces abortion, whereas produces mild to moderate renal damage. The aim of the present work was to study the progression of renal injury caused by a sublethal dose of Stx2, as well as renal recovery, in pregnant and non-pregnant rats, and to investigate whether pregnancy physiology may affect renal damage progression mediated by Stx2.
Renal function and histopathology was evaluated in pregnant rats intraperitoneally injected with a sublethal dose of Stx2 (0.5 ng/g bwt) at the early stage of gestation (day 8 of gestation), and results in these rats were compared over time with those observed in non-pregnant female rats injected with the same Stx2 dose. Hence, progression of cell proliferation and dedifferentiation in renal tubular epithelia was also investigated.
The sublethal dose of Stx2 induced abortion in pregnant rats as well as a significant more extended functional and histological renal injury in non-pregnant rats than in pregnant rats. Stx2 also caused decreased ability to concentrate urine in non-pregnant rats compared to their controls. However, renal water handling in pregnant rats was not altered by Stx2, and was significantly different than in non-pregnant rats. The greatest renal injury in both pregnant and non-pregnant rats was observed at 4 days post-Stx2 injection, and coincided with a significant increase in tubular epithelial proliferation. Expression of mesenchymal marker vimentin in tubular epithelia was consistent with the level of tubular damage, being higher in non-pregnant rats than in pregnant rats. Recovery from Stx2-induced kidney injury was faster in pregnant rats than in non-pregnant rats.
Adaptive mechanisms developed during pregnancy such as changes in water handle and renal hemodynamic may contribute to lessen the Stx2-induced renal injury, perhaps at the expense of fetal loss.
Cardiac Manifestation among Children with Hemolytic Uremic Syndrome
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The primary objectives of the study were to describe the association between cardiac manifestations and in-hospital mortality among children with hemolytic uremic syndrome.
Using the Pediatric Health Information System database, this retrospective, multicenter, cohort study identified the first hemolytic uremic syndrome-related inpatient visit among children ≤18 years (years 2004-2018). The frequency of selected cardiac manifestations and mortality rates were calculated. Multivariate analysis identified the association of specific cardiac manifestations and the risk of in-hospital mortality.
Among 3915 patients in the analysis, 238 (6.1%) had cardiac manifestations. A majority of patients (82.8%; n = 197) had 1 cardiac condition and 17.2% (n = 41) had ≥2 cardiac conditions. The most common cardiac conditions was pericardial disease (n = 102), followed by congestive heart failure (n = 46) and cardiomyopathy/myocarditis (n = 34). The percent mortality for patients with 0, 1, or ≥2 cardiac conditions was 2.1%, 17.3%, and 19.5%, respectively. Patients with any cardiac condition had an increased odds of mortality (OR, 9.74; P = .0001). In additional models, the presence of ≥2 cardiac conditions (OR, 9.90; P < .001), cardiac arrest (OR, 38.25; P < .001), or extracorporeal membrane oxygenation deployment (OR, 11.61; P < .001) were associated with increased risk of in-hospital mortality.
This study identified differences in in-hospital mortality based on the type of cardiac manifestations, with increased risk observed for patients with multiple cardiac involvement, cardiac arrest, and extracorporeal membrane oxygenation deployments.
Use of pulsed field gel electrophoresis genetic typing for tracing contamination with virulent Escherichia coli O157:H7 in beef-cattle producing farms
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Citation Excerpt :
Diseases caused by E. coli O157:H7 range from mild diarrhea to haemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS) that presents more severe complications in children, elderly and immune-compromised individuals (Noris and Remuzzi, 2005; Tarr et al., 2005; Gyles, 2007; Gould et al., 2009; Pennington, 2010). HUS is characterized by impairment of the glomerulus resulting in renal failure and most often leads to death (Gianantonio et al., 1964). The ability of this pathogen to cause the aforementioned diseases in particular HUS, has been attributed to the potential of individual cells to harbour a number pathogenic determinants (Gyles, 2007).
E. coli O157:H7 is an important causative agent of a variety of foodborne infections including hemorrhagic colitis (HC), hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) that may lead to renal failure in humans. The main source of infection is contaminated food of animal origin and a number of animal species especially cattle have been associated with this pathogen. Contamination usually occurs when faeces of animals get into contact with carcass during slaughtering. The aim of the present study was to determine the virulence profiles and genetic relationships of E. coli O157:H7 strains isolated from cattle some commercial farms in the North West Province, South Africa. A total of 260 faecal samples were collected from eight farms over a six-month period and assessed for the presence of E. coli O157:H7 through PCR analysis. Bacteria 16S rRNA gene fragments were amplified as an internal control while the rfb_O157 and flic_H7 gene PCR were used to confirm identities of isolates. STEC virulence genes stx1, stx2, eaeA and the hlyA were detected using PCR and the genetic relatedness of the isolates was determined using Pulse Field Gel electrophoresis (PFGE). A total of 69 (26.5%) E. coli O157:H7 isolates were detected in samples obtained from all the eight farms. A large proportions of the E. coli isolates possessed the stx₁ (66.7%) and stx₂ (97.1%) genes respectively. In addition, other accessory virulence genes eaeA and hlyA were detected in 30 (43.5%) and 43 (62.3%) of the E. coli isolates respectively. Pulsed-Filed Gel Electrophoresis (PFGE) analysis grouped these isolates into 6 clusters and the largest cluster contained 17 isolates originating from different farms. These results provide valid evidence that cattle harbour virulent and genetically similar E. coli strains particularly those belonging to the serotype O157 and therefore these animals may serve as possible source for zoonotic transfer of these pathogens to humans. The implication is that these isolates may have severe public health consequences on consumers.
Effects of shiga toxin 2 on cellular regeneration mechanisms in primary and three-dimensional cultures of human renal tubular epithelial cells
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Citation Excerpt :
Post-diarrheal hemolytic uremic syndrome (HUS) [1,2], due to Shiga toxin (Stx)-producing Escherichia coli (STEC), is a common cause of acute renal failure in children younger than 5 years [2].
Shiga toxin (Stx)-producing Escherichia coli (STEC) causes post-diarrheal Hemolytic Uremic Syndrome (HUS), which is one of the most common causes of acute renal failure in children in Argentine. The aim of the present work was to study the effects of Shiga toxin type 2 (Stx2) on regenerative mechanisms of primary cultures of human cortical renal tubular epithelial cells (HRTEC) and three-dimensional (3D) cultures of HRTEC. Primary cultures of HRTEC were able to develop tubular structures when grown in matrigel, which showed epithelial cells surrounding a central lumen resembling the original renal tubules. Exposure to Stx2 inhibited tubulogenesis in 3D-HRTEC cultures. Moreover, a significant increase in apoptosis, and decrease in cell proliferation was observed in tubular structures of 3D-HRTEC exposed to Stx2. A significant reduction in cell migration and vimentin expression levels was observed in HRTEC primary cultures exposed to Stx2, demonstrating that the holotoxin affected HRTEC dedifferentiation. Furthermore, a decreased number of cells expressing CD133 progenitor marker was found in HRTEC cultures treated with Stx2. The CD133 positive cells also expressed the Stx receptor globotriaosylceramide, which may explain their sensitivity to Stx2. In conclusion, Stx2 affects the regenerative processes of human renal tubular epithelial cells in vitro, by inhibiting cell dedifferentiation mechanisms, as well as tubules restoration. The development of 3D-HRTEC cultures that resemble original human renal proximal tubules is a novel in vitro model to study renal epithelial repair mechanisms after injury.
Genetic features of human and bovine Escherichia coli O157: H7 strains isolated in Argentina
2016, International Journal of Medical Microbiology
Citation Excerpt :
The clinical manifestations of infection range from symptom-free carriage to non-bloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS) (Gyles, 2007). HUS is a life-threatening condition characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure (Gianantonio et al., 1964). In Argentina, post-enteric HUS is endemic and approximately 400 new cases are reported annually.
Shiga toxin-producing Escherichia coli (STEC) are important food-borne pathogens associated with human diseases. In Argentina, O157:H7 is the dominant serotype in hemolytic uremic syndrome (HUS) cases. Previously, we have described the almost exclusive circulation of human E. coli O157 strains belonging to the hypervirulent clade 8 in Neuquén Province. The aim of the present study was to investigate, by a broad molecular characterization, if this particular distribution of E. coli O157 clades in Neuquén is similar to the situation in other regions of the country and if it may be originated in a similar profile in cattle, its main reservoir. Two-hundred and eighty O157 strains (54 bovine and 226 human) isolated between 2006 and 2008 in different regions of Argentina were studied. All strains harbored rfb_O157, fliC_H7, eae, and ehxA genes. The predominant genotype was stx_2a/stx_2c in human (76.1%) and bovine (55.5%) strains. All human isolates tested by Lineage-Specific Polymorphism Assay (LSPA-6), were lineage I/II; among bovine strains, 94.1% belonged to lineage I/II and 5.9% to lineage I. No LSPA-6 lineage II isolates were detected. Single nucleotide polymorphism (SNP) analysis has revealed the existence of nine clade phylogenetic groups. In our clinical strains collection, 87.6% belonged to the hypervirulent clade 8, and 12.4% were classified as clade 4/5. In bovine isolates, 59.3% strains were clade 8, 33.3% clade 4/5 and 7.4% clade 3. More than 80% of human strains showed the presence of 6 of the 7 virulence determinants described in the TW14359 O157 strain associated with the raw spinach outbreak in the U.S. in 2006. More than 80% of bovine strains showed the presence of 3 of these factors. The q₉₃₃ allele, which has been related to high toxin production, was present in 98.2% of clinical strains and 75.9% of the bovine isolates. The molecular characterization of human STEC O157 strains allows us to conclude that the particular situation previously described for Neuquén Province, may actually be a characteristic of the whole country. These genetic features are quite similar to those observed in the bovine reservoir and may be derived from it. This data confirms that, unlike the rest of the world, in Argentina most of the STEC O157 strains present in cattle may cause human infections of varying severity and the marked virulence described for these strains may be related to the high incidence of HUS in our country.
Inhibition of water absorption and selective damage to human colonic mucosa induced by Shiga toxin-2 are enhanced by Escherichia coli O157:H7 infection
2015, International Journal of Medical Microbiology
Citation Excerpt :
Shiga toxin-producing Escherichia coli (STEC) strains are responsible for a variety of clinical syndromes including bloody and non-bloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS) (Karmali et al., 1985). HUS develops in 5–10% of children several days after bloody diarrhea and is a systemic disease characterized by thrombotic microangiopathy, hemolytic anemia, thrombocytopenia, and acute renal failure (Gianantonio et al., 1964; Boyce et al., 1995). Although multiple serotypes of STEC have been isolated from hemorrhagic colitis cases, E. coli O157:H7 is by far the most prevalent serotype associated with HUS.
Shiga toxin-producing Escherichia coli (STEC) strains are responsible for a variety of clinical syndromes including bloody and non-bloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Although multiple serotypes of STEC have been isolated from hemorrhagic colitis cases, E. coli O157:H7 is by far the most prevalent serotype associated with HUS. Shiga toxin is the major virulence factor of E. coli O157:H7 and is responsible for the more severe symptoms of the infection. However, the mechanisms involved in the pathogenesis of diarrhea mediated by Stx2 are not well known. In this study, we have determined the effects of E. coli O157:H7 strain 125/99 wild type (wt) on the human colonic mucosa mounted in an Ussing chamber. In response to 125/99wt, an inhibition of water absorption across human colonic mucosa was observed. Histological sections showed severe necrosis with detachment of the surface epithelium, mononuclear inflammatory infiltrate and loss of goblet cells after 1 h of incubation with 125/99wt. These alterations were not observed with the isogenic mutant strain lacking stx2 or with the filter-sterilized culture supernatant from the 125/99wt strain. These results indicate that the cell damages in human colon are induced by Stx2, and that Stx2 production is increased by the interaction with bacterial cells. Identification of host cell-derived factors responsible for increasing Stx2 can lead to new strategies for modulating STEC infections.

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^*: Supported in part by a grant from the Consejo Nacional de Investigaciones Cientificas y Técnicas.

^*: Associate in Research (Consejo Nacional de Investigaciones).

¹: San Juan 300, Martinez (FCGBM) Buenos Aires, Argentina.

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The hemolytic-uremic syndrome*

J. Pediat.

J. Pediat.

Blood

Blood

Hamolytisch-uramische Syndrome: bilaterale Nierenrindennekrosen bei Akuten erworbenen hamolytischen Anamien

Schweiz. med. Wchnschr.

La Micro-angiophatie Trombotique du rein chez l'enfant

Semaine hop. Paris

Syndrome of hemolysis thrombopenia and nephropathy in infancy

Pediatrics

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Pediatrics

Acute haemolytic anaemia with distortion and fragmentation of erythrocytes in children

Brit. J. Haemat.

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The syndrome of hemolytic anemia thrombocytopenia and uremia

A. M. A. J. Dis. Child.

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Pediatria

Empleo del gel de poliacrilamide en la electroforesis de las proteinas sericas. I. Metodo

Medicina

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Medicina