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Wong W, Prestidge C, Dickens A, Ronaldson J. Diarrhoea-associated haemolytic uraemic syndrome and Shiga toxin-producing Escherichia coli infections in New Zealand children: Clinical features and short-term complications from a 23-year cohort study. J Paediatr Child Health 2023; 59:493-498. [PMID: 36655863 DOI: 10.1111/jpc.16332] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 12/26/2022] [Accepted: 01/08/2023] [Indexed: 01/20/2023]
Abstract
BACKGROUND Diarrhoea-associated haemolytic uraemic syndrome (D+HUS) is an important cause of acute kidney injury (AKI) in young children and it is most commonly associated with Shiga toxin-producing Escherichia coli (STEC). Gastrointestinal infections caused by STEC have been increasing in New Zealand over the past two decades, but little is known regarding the acute and short-term outcomes of New Zealand children who develop D+HUS. AIM To describe the clinical characteristics, complications and short-term outcomes of New Zealand children with D+HUS identified between 1 January 1998 and 31 December 2020. METHODS The New Zealand Paediatric Surveillance Unit sends out a monthly survey to all practising paediatricians regarding conditions under active surveillance. Paediatricians caring for a child aged 0-15 years of age with D+HUS over the prior month were requested to report their patient. Reporting clinicians were then contacted by the principal investigator and sent a questionnaire requesting patient clinical and laboratory information. RESULTS Two hundred and twenty-six children had D+HUS; median age 2.8 years (interquartile range 1.7-4.9). Acute dialysis was required in 128/226 (56.2%) of children for a median of 9 days (range 1-38). Children with shorter diarrhoeal prodrome, higher neutrophil count and haemoglobin had a longer duration of dialysis. Seizures occurred in 31/226 (13.7%) and were not associated with a greater HUS severity score. Acute mortality was 1.3%, all resulting from thrombotic microangiopathic cerebral injury. CONCLUSION D+HUS is a major cause of AKI in previously healthy young children. Earlier recognition of STEC infections in young children may reduce the need for dialysis and other extra-renal complications. The New Zealand incidence of acute dialysis, other major complications and mortality are consistent with other reported studies.
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Affiliation(s)
- William Wong
- Department of Paediatric Nephrology, Starship Children's Health, Te Whatu Ora Auckland, Auckland, New Zealand
| | - Chanel Prestidge
- Department of Paediatric Nephrology, Starship Children's Health, Te Whatu Ora Auckland, Auckland, New Zealand
| | - Amanda Dickens
- Department of Paediatric Nephrology, Starship Children's Health, Te Whatu Ora Auckland, Auckland, New Zealand
| | - Jane Ronaldson
- Department of Paediatric Nephrology, Starship Children's Health, Te Whatu Ora Auckland, Auckland, New Zealand
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2
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Riedl Khursigara M, Matsuda-Abedini M, Radhakrishnan S, Hladunewich MA, Lemaire M, Teoh CW, Noone D, Licht C. A Guide for Adult Nephrologists and Hematologists to Managing Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy in Teens Transitioning to Young Adults. Adv Chronic Kidney Dis 2022; 29:231-242. [PMID: 36084970 DOI: 10.1053/j.ackd.2022.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Accepted: 04/11/2022] [Indexed: 11/11/2022]
Abstract
Atypical hemolytic uremic syndrome and C3 glomerulopathy/immune complex membranoproliferative glomerulonephritis are ultra-rare chronic, complement-mediated diseases with childhood manifestation in a majority of cases. Transition of clinical care of patients from pediatric to adult nephrologists-typically with controlled disease in native or transplant kidneys in case of atypical hemolytic uremic syndrome and often with chronic progressive disease despite treatment efforts in case of C3 glomerulopathy/immune complex membranoproliferative glomerulonephritis-identifies a challenging juncture in the journey of these patients. Raising awareness for the vulnerability of this patient cohort; providing education on disease pathophysiology and management including the use of new, high-precision complement antagonists; and establishing an ongoing dialog of patients, families, and all members of the health care team involved on either side of the age divide will be inevitable to ensure optimal patient outcomes and a safe transition of these patients to adulthood.
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Affiliation(s)
| | - Mina Matsuda-Abedini
- Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Paediatrics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Seetha Radhakrishnan
- Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Paediatrics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Michelle A Hladunewich
- Division of Nephrology and Obstetric Medicine, Department of Medicine, Sunnybrook Health Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Mathieu Lemaire
- Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Paediatrics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada
| | - Chia Wei Teoh
- Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Paediatrics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Damien Noone
- Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Paediatrics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Christoph Licht
- Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Paediatrics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
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Kumar S, Bhagia G, Kaae J. A Rare Case of Atypical Hemolytic Uremia Syndrome Triggered by Influenza Vaccination. Cureus 2022; 14:e23577. [PMID: 35494971 PMCID: PMC9045680 DOI: 10.7759/cureus.23577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/28/2022] [Indexed: 11/08/2022] Open
Abstract
Atypical hemolytic uremic syndrome (aHUS) occurs in patients with defective alternative complement pathways, making them susceptible to thrombotic microangiopathy (thrombocytopenia, intravascular hemolysis, and renal failure), and is usually triggered by infectious agents. Influenza and Streptococcus pneumonia are known triggers for aHUS. However, influenza vaccination triggering aHUS is rarely reported. We present a 30-year-old male who presented with chills, abdominal discomfort, and night sweats after receiving the influenza vaccine. The patient had thrombocytopenia, elevated creatinine, blood urea nitrogen, liver enzymes, and bilirubin with schistocytes with peripheral smear. ADAMTS13 activity was normal so the patient was diagnosed with aHUS. The patient improved with eculizumab and was ultimately found to have a mutation in CD46, which made him susceptible to aHUS. This case shows patients with dysregulated alternative complement pathways may be predisposed to develop aHUS after receiving influenza vaccination.
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Valid Presumption of Shiga Toxin-Mediated Damage of Developing Erythrocytes in EHEC-Associated Hemolytic Uremic Syndrome. Toxins (Basel) 2020; 12:toxins12060373. [PMID: 32512916 PMCID: PMC7354503 DOI: 10.3390/toxins12060373] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 06/02/2020] [Accepted: 06/03/2020] [Indexed: 02/06/2023] Open
Abstract
The global emergence of clinical diseases caused by enterohemorrhagic Escherichia coli (EHEC) is an issue of great concern. EHEC release Shiga toxins (Stxs) as their key virulence factors, and investigations on the cell-damaging mechanisms toward target cells are inevitable for the development of novel mitigation strategies. Stx-mediated hemolytic uremic syndrome (HUS), characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal injury, is the most severe outcome of an EHEC infection. Hemolytic anemia during HUS is defined as the loss of erythrocytes by mechanical disruption when passing through narrowed microvessels. The formation of thrombi in the microvasculature is considered an indirect effect of Stx-mediated injury mainly of the renal microvascular endothelial cells, resulting in obstructions of vessels. In this review, we summarize and discuss recent data providing evidence that HUS-associated hemolytic anemia may arise not only from intravascular rupture of erythrocytes, but also from the extravascular impairment of erythropoiesis, the development of red blood cells in the bone marrow, via direct Stx-mediated damage of maturing erythrocytes, leading to “non-hemolytic” anemia.
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ZAKα Recognizes Stalled Ribosomes through Partially Redundant Sensor Domains. Mol Cell 2020; 78:700-713.e7. [PMID: 32289254 DOI: 10.1016/j.molcel.2020.03.021] [Citation(s) in RCA: 102] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 01/31/2020] [Accepted: 03/13/2020] [Indexed: 11/22/2022]
Abstract
Impairment of ribosome function activates the MAPKKK ZAK, leading to activation of mitogen-activated protein (MAP) kinases p38 and JNK and inflammatory signaling. The mechanistic basis for activation of this ribotoxic stress response (RSR) remains completely obscure. We show that the long isoform of ZAK (ZAKα) directly associates with ribosomes by inserting its flexible C terminus into the ribosomal intersubunit space. Here, ZAKα binds helix 14 of 18S ribosomal RNA (rRNA). An adjacent domain in ZAKα also probes the ribosome, and together, these sensor domains are critically required for RSR activation after inhibition of both the E-site, the peptidyl transferase center (PTC), and ribotoxin action. Finally, we show that ablation of the RSR response leads to organismal phenotypes and decreased lifespan in the nematode Caenorhabditis elegans (C. elegans). Our findings yield mechanistic insight into how cells detect ribotoxic stress and provide experimental in vivo evidence for its physiological importance.
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Hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli in children: incidence, risk factors, and clinical outcome. Pediatr Nephrol 2020; 35:1749-1759. [PMID: 32323005 PMCID: PMC7385025 DOI: 10.1007/s00467-020-04560-0] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 03/22/2020] [Accepted: 03/30/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND Hemolytic uremic syndrome (HUS) is a multisystemic disease. In a nationwide study, we characterized the incidence, clinical course, and prognosis of HUS caused by Shiga toxin (Stx)-producing Escherichia coli (STEC) strains with emphasis on risk factors, disease severity, and long-term outcome. METHODS The data on pediatric HUS patients from 2000 to 2016 were collected from the medical records. STEC isolates from fecal cultures of HUS and non-HUS patients were collected from the same time period and characterized by whole genome sequencing analysis. RESULTS Fifty-eight out of 262 culture-positive cases developed verified (n = 58, 22%) STEC-HUS. Another 29 cases had probable STEC-HUS, the annual incidence of STEC-HUS being 0.5 per 100,000 children. Eleven different serogroups were detected, O157 being the most common (n = 37, 66%). Age under 3 years (OR 2.4), stx2 (OR 9.7), and stx2a (OR 16.6) were found to be risk factors for HUS. Fifty-five patients (63%) needed dialysis. Twenty-nine patients (33%) developed major neurological symptoms. Complete renal recovery was observed in 57 patients after a median 4.0 years of follow-up. Age under 3 years, leukocyte count over 20 × 109/L, and need for dialysis were predictive factors for poor renal outcome. CONCLUSIONS Age under 3 years, stx2, and stx2a were risk factors for HUS in STEC-positive children. However, serogroup or stx types did not predict the renal outcome or major CNS symptoms.
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Balgradean M, Croitoru A, Leibovitz E. An outbreak of hemolytic uremic syndrome in southern Romania during 2015-2016: Epidemiologic, clinical, laboratory, microbiologic, therapeutic and outcome characteristics. Pediatr Neonatol 2019; 60:87-94. [PMID: 29807724 DOI: 10.1016/j.pedneo.2018.04.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Revised: 03/16/2018] [Accepted: 04/30/2018] [Indexed: 10/17/2022] Open
Abstract
BACKGROUND AND AIMS To describe the epidemiologic, clinical, microbiological, therapeutic and outcome characteristics of a HUS outbreak occurring in southern Romania from 2015 to 2016. METHODS We retrospectively collected data from the medical records of all HUS cases hospitalized at the pediatric nephrology department of Marie Curie Children's Hospital of Bucharest, Romania. RESULTS There were 32 HUS cases (19 girls/13 boys, 87.6% <2 years), all associated with diarrhea (bloody in 13, 40.6%). Thirteen (40.6%) and 4 (12.5%) patients had oliguria and anuria at admission. Extreme pallor, generalized edema, vomiting, dehydration, fever and seizures were found in 100%, 56.3%, 31.3%, 31.3%, 25% and 9.4% of patients, respectively. E. coli and STEC were identified in the stools of 6 and 8 patients, respectively; E. coli O26 and O157 infection were documented serologically in 10 and 3 children, respectively. There were 15/32 (46.9%) patients with confirmed HUS. Eighteen (56.3%) patients were hypertensive; other complications included infections, left ventricular hypertrophy, cardiopulmonary arrest, seizures and encephalopathy in 62.5%, 37.5%, 28.3%, 18.8% and 12.5%, respectively. Peritoneal dialysis and hemodialysis were performed in 23 (72%) and 2 patients, respectively. Three patients (9.4%) died early during hospitalization. A 6-12-month follow-up of 26 patients revealed that 65.4% had post-HUS sequelae (persistent hypertension and chronic renal failure in 34.6% and 30.8%, respectively). CONCLUSIONS The principal STEC serotype involved was O26:H11 and the number of confirmed HUS cases reached half of the patients. Compared with the medical literature, this outbreak had a higher rate of complications and renal sequelae and was associated with a high fatality rate.
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Affiliation(s)
- Mihaela Balgradean
- Nephrology & Dialysis Department, Children's Emergency Hospital " M. S. Curie", "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
| | - Anca Croitoru
- Nephrology & Dialysis Department, Children's Emergency Hospital " M. S. Curie", "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
| | - Eugene Leibovitz
- Pediatric Infectious Disease Unit, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
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9
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Abstract
Atypical hemolytic uremic syndrome (aHUS) is characterized by uncontrolled complement activation leading to thrombotic microangiopathy and severe end-organ damage. The most common trigger for an episode of aHUS in the background of genetic deregulation of the alternative complement pathway is systemic infection. There are only 4 reported cases of aHUS triggered by influenza B thus far. Current accepted therapies for aHUS include plasma exchange and eculizumab. We describe a unique patient with aHUS with a rare membrane cofactor protein mutation triggered by influenza B infection, who achieved complete remission with treatment with high-dose corticosteroids after failure of plasmapheresis.
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10
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Nicolay JP, Thorn V, Daniel C, Amann K, Siraskar B, Lang F, Hillgruber C, Goerge T, Hoffmann S, Gorzelanny C, Huck V, Mess C, Obser T, Schneppenheim R, Fleming I, Schneider MF, Schneider SW. Cellular stress induces erythrocyte assembly on intravascular von Willebrand factor strings and promotes microangiopathy. Sci Rep 2018; 8:10945. [PMID: 30026593 PMCID: PMC6053440 DOI: 10.1038/s41598-018-28961-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Accepted: 07/01/2018] [Indexed: 11/17/2022] Open
Abstract
Microangiopathy with subsequent organ damage represents a major complication in several diseases. The mechanisms leading to microvascular occlusion include von Willebrand factor (VWF), notably the formation of ultra-large von Willebrand factor fibers (ULVWFs) and platelet aggregation. To date, the contribution of erythrocytes to vascular occlusion is incompletely clarified. We investigated the platelet-independent interaction between stressed erythrocytes and ULVWFs and its consequences for microcirculation and organ function under dynamic conditions. In response to shear stress, erythrocytes interacted strongly with VWF to initiate the formation of ULVWF/erythrocyte aggregates via the binding of Annexin V to the VWF A1 domain. VWF-erythrocyte adhesion was attenuated by heparin and the VWF-specific protease ADAMTS13. In an in vivo model of renal ischemia/reperfusion injury, erythrocytes adhered to capillaries of wild-type but not VWF-deficient mice and later resulted in less renal damage. In vivo imaging in mice confirmed the adhesion of stressed erythrocytes to the vessel wall. Moreover, enhanced eryptosis rates and increased VWF binding were detected in blood samples from patients with chronic renal failure. Our study demonstrates that stressed erythrocytes have a pronounced binding affinity to ULVWFs. The discovered mechanisms suggest that erythrocytes are essential for the pathogenesis of microangiopathies and renal damage by actively binding to ULVWFs.
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Affiliation(s)
- Jan P Nicolay
- Department of Dermatology, Venereology and Allergy, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany. .,Division of Immunogenetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
| | - Verena Thorn
- Department of Dermatology, Venereology and Allergy, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany
| | - Christoph Daniel
- Department of Nephropathology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Erlangen, Germany
| | - Kerstin Amann
- Department of Nephropathology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Erlangen, Germany
| | | | - Florian Lang
- Department of Physiology, University of Tübingen, Tübingen, Germany
| | - Carina Hillgruber
- Department of Dermatology, University Hospital Münster, Münster, Germany
| | - Tobias Goerge
- Department of Dermatology, University Hospital Münster, Münster, Germany
| | - Stefan Hoffmann
- Institute of Plant Biology and Biotechnology (IBBP), Westfälische Wilhelms-Universität Münster, Münster, Germany
| | - Christian Gorzelanny
- Department of Dermatology, Venereology and Allergy, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany.,Department of Dermatology and Venerology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Volker Huck
- Department of Dermatology, Venereology and Allergy, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany.,Department of Dermatology and Venerology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christian Mess
- Department of Dermatology and Venerology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Tobias Obser
- Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Reinhard Schneppenheim
- Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ingrid Fleming
- Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany
| | | | - Stefan W Schneider
- Department of Dermatology and Venerology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Borkar D, Schutt C, Verghese P. Renal Recovery Years After Initial Diagnosis of Hemolytic Uremic Syndrome. Clin Pediatr (Phila) 2018; 57:861-864. [PMID: 28931327 DOI: 10.1177/0009922817732621] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- Deeksha Borkar
- 1 University of Minnesota Medical Center, Minneapolis, MN, USA
| | - Christina Schutt
- 2 Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA
| | - Priya Verghese
- 1 University of Minnesota Medical Center, Minneapolis, MN, USA
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12
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Janapatla RP, Chen CL, Hsu MH, Liao WT, Chiu CH. Immunization with pneumococcal neuraminidases NanA, NanB and NanC to generate neutralizing antibodies and to increase survival in mice. J Med Microbiol 2018; 67:709-723. [PMID: 29557769 DOI: 10.1099/jmm.0.000724] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Purpose. Pneumococcal virulence protein-based vaccines can provide serotype-independent protection against pneumococcal infections. Many studies, including clinical observational studies on Thomsen-Friedenrich antigen exposure and haemolytic uremic syndrome, defined the role of neuraminidases NanA, NanB and NanC in host-pneumococcus interaction. Since neuraminidases are major virulence proteins, they are potential targets for both vaccines and small molecule inhibitors. Here we explored the utility of three neuraminidases as protein vaccine antigens to generate neutralizing antibodies and to increase survival following pneumococcal infections.Methodology. Rabbits and mice were immunized subcutaneously with enzymatically active recombinant NanA, NanB and NanC as individual or a combination of the three neuraminidases. Antisera titres were determined by ELISA. Neuraminidase activity inhibition by antiserum was tested by peanut lectin and flow cytometry. Clinical isolates with serotype 3, 6B, 14, 15B, 19A and 23F were used to infect immunized mice by tail vein injection.Results/Key findings. Presence of high levels of IgG antibodies in antisera against NanA, NanB and NanC indicates that all of the three neuraminidases are immunogenic vaccine antigens. To generate potent NanA neutralizing antibodies, both lectin and catalytic domains are essential, whereas for NanB and NanC a single lectin domain is sufficient. Immunization with triple neuraminidases increased the survival of mice when intravenously challenged with clinical isolates of serotype 3 (40 %), 6B (60 %), 15B (60 %), 19A (40 %) and 23F (30 %).Conclusion. We recommend the inclusion of three pneumococcal neuraminidases in future protein vaccine formulations to prevent invasive pneumococcal infection caused by various serotypes.
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Affiliation(s)
| | - Chyi-Liang Chen
- Molecular Infectious Diseases Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
| | - Mei-Hua Hsu
- Molecular Infectious Diseases Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
| | - Wan-Ting Liao
- Molecular Infectious Diseases Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
| | - Cheng-Hsun Chiu
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan, ROC.,Molecular Infectious Diseases Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
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Postdiarrheal hemolytic and uremic syndrome with severe multiorgan involvement and associated early risk factors. Arch Pediatr 2018; 25:118-125. [PMID: 29395881 DOI: 10.1016/j.arcped.2017.12.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2017] [Revised: 11/08/2017] [Accepted: 12/10/2017] [Indexed: 12/24/2022]
Abstract
AIM Identifying early clinical and biological factors associated with severe forms of postdiarrheal hemolytic uremic syndrome (D+HUS) that may help practitioners determine appropriate treatment. METHODS This retrospective study was conducted in 49 children with D+HUS between 2001 and 2011. Severe forms were defined as occurrence of one of the following conditions: death, major neurological involvement, cardiovascular involvement, and/or the presence of sequelae (neurological, cardiovascular, pancreatic, or renal). RESULTS During the acute phase, 35 children exhibited at least one type of extrarenal involvement including 13 severe forms with a median delayed occurrence after admission of 4.5 days (range: 1-8) for comatose children and 5 days (range: 2-6) for cardiovascular involvement; 32 children required dialysis and three died. In multivariate analysis, (i) major neurological involvement (n=13), (ii) dialysis (n=32), and (iii) sequelae (n=12) were associated with (i) fever during the prodromal phase requiring dialysis at admission, (ii) C-reactive protein level (CRP) >22mg/L at admission, and (iii) major neurological involvement and a white blood cell count (WBC)>20×103/mm3 during the acute stage, respectively. CONCLUSIONS D+HUS is a multiorgan disease with a delayed occurrence of life-threatening extrarenal organ involvement. Severe forms appear to be associated with early biological and clinical inflammatory parameters.
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Balestracci A, Toledo I, Meni Battaglia L, de Lillo L, More N, Cao G, Alvarado C. Postdiarrhoeal haemolytic uraemic syndrome without thrombocytopenia. Nefrologia 2017; 37:508-514. [PMID: 28946963 DOI: 10.1016/j.nefro.2016.12.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Revised: 12/01/2016] [Accepted: 12/10/2016] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Thrombocytopenia is a hallmark of postdiarrhoeal haemolytic uraemic syndrome (D+ HUS), although it can be transient and therefore undetected. There is scarce information regarding the prevalence and the course of the disease in children with D+ HUS without thrombocytopenia. OBJECTIVE To determine the prevalence of D+ HUS without thrombocytopenia and to describe the clinical characteristics of a series of children with this condition. PATIENTS AND METHODS The medical records of patients with D+ HUS hospitalised between 2000 and 2016 were reviewed to identify those without thrombocytopenia (>150,000mm3). Demographic, clinical and laboratory parameters of the selected cases were collected and descriptively analysed. RESULTS Nine cases (5.6%) without thrombocytopenia were identified among 161 patients hospitalised during the study period. Median age at diagnosis was 17 months (7-32) and median prodromal symptom duration was 15 days (7-21). Eight patients maintained normal urine output while the remaining one required dialysis. No patient presented with severe extrarenal compromise and/or hypertension. CONCLUSIONS The prevalence of non-thrombocytopenic D+ HUS was 5.6% and most cases occurred with mild forms of the disease; however, the need for dialysis in one of them indicated that normalisation of platelet count is not always an accurate marker for disease remittance. Our results also confirm that the time of onset of D+ HUS in patients without thrombocytopenia is usually delayed with respect to the initial intestinal symptoms; thus, heightened diagnostic suspicion is necessary.
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Affiliation(s)
- Alejandro Balestracci
- Unidad de Nefrología, Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires, Argentina.
| | - Ismael Toledo
- Unidad de Nefrología, Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires, Argentina
| | - Luciana Meni Battaglia
- Unidad de Nefrología, Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires, Argentina
| | - Leonardo de Lillo
- Departamento de Pediatría, Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires, Argentina
| | - Natalia More
- Departamento de Pediatría, Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires, Argentina
| | - Gabriel Cao
- División de Patología, Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires, Argentina
| | - Caupolican Alvarado
- Unidad de Nefrología, Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires, Argentina
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15
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Kreuzer M, Sollmann L, Ruben S, Leifheit-Nestler M, Fischer DC, Pape L, Haffner D. Endothelial dysfunction during long-term follow-up in children with STEC hemolytic-uremic syndrome. Pediatr Nephrol 2017; 32:1005-1011. [PMID: 28180952 DOI: 10.1007/s00467-016-3574-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Revised: 12/16/2016] [Accepted: 12/20/2016] [Indexed: 11/25/2022]
Abstract
BACKGROUND Shiga-toxin-producing Escherichia coli (STEC)-associated hemolytic-uremic syndrome (HUS) is a major cause of acute kidney injury (AKI), especially in children. Its long-term outcome with respect to endothelial damage remains largely elusive. METHODS This was a cross-sectional study in 26 children who had suffered from STEC-HUS in the past and achieved a complete recovery of renal function (eGFR >90 ml/min/1.73 m2). Skin microcirculation after local heating was assessed by laser Doppler fluximetry, carotid-femoral pulse wave velocity (PWV), carotid intima media thickness (cIMT), 24-h ambulatory blood pressure, and angiopoietin (Ang) 1 and 2 serum levels after a median follow-up period of 6.1 years. The results were compared to those of healthy controls. RESULTS All patients were normotensive, mean eGFR was 102 (range 91-154) ml/min/1.73 m2, and 13 of the 26 patients showed albuminuria. Endothelial dysfunction was present in 13 patients, and the mean serum Ang2/Ang1 ratio was increased compared to healthy children (each p < 0.05). In contrast, mean values for PWV and cIMT in the patients did not differ from those of the controls. Endothelial dysfunction was significantly associated with younger age at STEC-HUS manifestation, time after HUS, and presence of albuminuria. CONCLUSION The results of this study highlight the need for long-term follow-up of STEC-HUS patients even after complete recovery of eGFR and lack of hypertension with respect to microvascular damage.
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Affiliation(s)
- Martin Kreuzer
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
| | - Laura Sollmann
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany
| | - Stephan Ruben
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany
| | - Maren Leifheit-Nestler
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany
| | | | - Lars Pape
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany
| | - Dieter Haffner
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany
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16
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van Hoeve K, Vandermeulen C, Van Ranst M, Levtchenko E, van den Heuvel L, Mekahli D. Occurrence of atypical HUS associated with influenza B. Eur J Pediatr 2017; 176:449-454. [PMID: 28110418 DOI: 10.1007/s00431-017-2856-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2016] [Revised: 12/29/2016] [Accepted: 01/10/2017] [Indexed: 12/27/2022]
Abstract
UNLABELLED Hemolytic uremic syndrome (HUS) is a disease characterized by thrombotic microangiopathy with a triad of non-immune hemolytic anemia, thrombocytopenia, and renal impairment. Approximately 10% of cases of HUS are classified as atypical (aHUS). While today many genetically forms of aHUS pathology are known, only about 50% of carriers precipitate the disease. The reason remains unclear, and triggering events like intercurrent infections have been postulated. In rare cases, influenza A is the known trigger of aHUS; however, no cases of influenza B have been reported. CONCLUSION We describe for the first time that influenza B strain as a trigger for aHUS in children with primary hereditary forms. We also showed in our three cases that immunization appears to be safe; however, this needs to be confirmed in a larger cohort. What is Known: • Known triggers of aHUS are infectious specimen. • Influenza A-associated aHUS cases are rarely published. What is New: • aHUS can be triggered by influenza B virus infection. • Influenza vaccination of patients with aHUS appears safe.
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Affiliation(s)
- Karen van Hoeve
- Department of Pediatric Nephrology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
| | - Corinne Vandermeulen
- University Vaccinology Center, KU Leuven - University of Leuven, 3000, Leuven, Belgium
| | - Marc Van Ranst
- Department of Microbiology and Immunology, KU Leuven - Rega Institute, 3000, Leuven, Belgium
| | - Elena Levtchenko
- Department of Pediatric Nephrology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.,Laboratory of Pediatrics, KU Leuven - University of Leuven, 3000, Leuven, Belgium
| | | | - Djalila Mekahli
- Department of Pediatric Nephrology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.,Laboratory of Pediatrics, KU Leuven - University of Leuven, 3000, Leuven, Belgium
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17
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Bajracharya P, Jain A, Baracco R, Mattoo TK, Kapur G. Atypical hemolytic uremic syndrome: a clinical conundrum. Pediatr Nephrol 2016; 31:1615-24. [PMID: 27139899 DOI: 10.1007/s00467-016-3369-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2015] [Revised: 03/04/2016] [Accepted: 03/07/2016] [Indexed: 01/15/2023]
Abstract
BACKGROUND Patients negative for Shiga toxin-producing E. coli (STEC) are categorized as having atypical hemolytic uremic syndrome (HUS) and are associated with an increased risk for complement mutations and poorer prognosis compared with typical HUS. However, STEC identification is limited by the natural history of HUS. METHODS The current study is aimed at identifying HUS patients with poor outcomes based on the presence or absence of diarrhea (D) or Shiga toxin (S). A single-center retrospective review (2003-2012) of 42 HUS patients (follow-up 31.3 ± 38.7 months) was carried out. HUS was managed clinically with supportive treatments such as dialysis, plasma therapy, and eculizumab. RESULTS There was no significant difference in the D+S+ (31 %), D+S- (50 %) and D-S- (19 %) groups in the outcome variables of chronic kidney disease stages I-II (100 % vs 81 % vs 67 %) and proteinuria at follow-up (20 % vs 12.5 % vs 33.3 %), hospitalization duration (16.0 ± 8.7 vs 18.1 ± 9.5 vs 23.7 ± 12.9 days); dialysis requirement (50 % vs 81 % vs 66.7 %), and dialysis duration (10.2 ± 1.9 vs 33.3 ± 72.8 vs 10.3 ± 8.1 days). There was no significant difference in study outcomes in STEC+ (59 %) versus STEC- (41 %) groups. Genetic testing was performed in 12 % of HUS patients based on age, recurrent HUS, familial HUS, persistently low C3, or prolonged dialysis, and 80 % of the patients tested were positive for genetic mutations. CONCLUSIONS Our study does not show poorer outcomes in STEC- HUS. Indications and the cost-effectiveness of genetic testing, eculizumab, and plasmapheresis in STEC- HUS need to be evaluated further.
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Affiliation(s)
- Prabesh Bajracharya
- Children's Hospital of Michigan, Wayne State University, 3901 Beaubien Boulevard, Detroit, MI, 48201, USA
| | - Amrish Jain
- Children's Hospital of Michigan, Wayne State University, 3901 Beaubien Boulevard, Detroit, MI, 48201, USA
| | - Rossana Baracco
- Children's Hospital of Michigan, Wayne State University, 3901 Beaubien Boulevard, Detroit, MI, 48201, USA
| | - Tej K Mattoo
- Children's Hospital of Michigan, Wayne State University, 3901 Beaubien Boulevard, Detroit, MI, 48201, USA
| | - Gaurav Kapur
- Children's Hospital of Michigan, Wayne State University, 3901 Beaubien Boulevard, Detroit, MI, 48201, USA.
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18
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Huzmeli C, Candan F, Seker A, Yildiz E, Terzi H, Kayatas M. C3 mesangial proliferative glomerulonephritis initially presenting with atypical hemolytic uremic syndrome: a case report. J Med Case Rep 2016; 10:206. [PMID: 27460033 PMCID: PMC4962343 DOI: 10.1186/s13256-016-0992-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Accepted: 07/01/2016] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Hemolytic uremic syndrome is characterized by acute renal failure, thrombocytopenia, and Coombs-negative hemolytic anemia. In C3 mesangial proliferative glomerulonephritis, an increase in mesangial cell proliferation without thickening in the glomerular capillary wall can be seen under light microscopy, but the definitive diagnosis is made with the immunohistologic demonstration of isolated C3 deposits in the mesangium. C3 glomerulonephritis may be detected in childhood; however, in this case report we describe the first case of isolated C3 glomerulonephritis together with atypical hemolytic uremic syndrome in an adult patient. CASE PRESENTATION Here we present a case of a 27-year-old white man with anuria who was hospitalized after being diagnosed as having hemolytic uremic syndrome accompanied by acute renal failure. Renal biopsy results revealed C3 glomerulonephritis. There was a complete recovery of renal function after hemodialysis, and prednisolone and plasma exchange treatment. CONCLUSIONS C3 glomerulopathy is distinct from atypical hemolytic uremic syndrome although both diseases are due to abnormal control of the alternative complement pathway. In atypical hemolytic uremic syndrome activation of complement occurs on glomerular or microvascular endothelium causing a thrombotic microangiopathy; in most cases, no electron-dense deposits are seen on electron microscopy and glomerular C3 is not detected on immunofluorescence.
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Affiliation(s)
- Can Huzmeli
- Department of Nephrology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey.
| | - Ferhan Candan
- Department of Nephrology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey
| | - Ayse Seker
- Department of Nephrology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey
| | - Esin Yildiz
- Department of Pathology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey
| | - Hatice Terzi
- Department of Hematology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey
| | - Mansur Kayatas
- Department of Nephrology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey
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19
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Jenssen GR, Vold L, Hovland E, Bangstad HJ, Nygård K, Bjerre A. Clinical features, therapeutic interventions and long-term aspects of hemolytic-uremic syndrome in Norwegian children: a nationwide retrospective study from 1999-2008. BMC Infect Dis 2016; 16:285. [PMID: 27297224 PMCID: PMC4906913 DOI: 10.1186/s12879-016-1627-7] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2016] [Accepted: 06/07/2016] [Indexed: 12/25/2022] Open
Abstract
Background Hemolytic-uremic syndrome (HUS) is a clinical triad of microangiopathic hemolytic anemia, impaired renal function and thrombocytopenia, primarily affecting pre-school-aged children. HUS can be classified into diarrhea-associated HUS (D+HUS), usually caused by Shiga toxin-producing Escherichia coli (STEC), and non-diarrhea-associated HUS (D−HUS), both with potentially serious acute and long-term complications. Few data exists on the clinical features and long-term outcome of HUS in Norway. The aim of this paper was to describe these aspects of HUS in children over a 10-year period. Methods We retrospectively collected data on clinical features, therapeutic interventions and long-term aspects directly from medical records of all identified HUS cases <16 years of age admitted to Norwegian pediatric departments from 1999 to 2008. Cases of D+HUS and D−HUS are described separately, but no comparative analyses were possible due to small numbers. Descriptive statistics are presented in proportions and median values with ranges, and/or summarized in text. Results Forty seven HUS cases were identified; 38 D+HUS and nine D−HUS. Renal complications were common; in the D+HUS and D−HUS group, 29/38 and 5/9 developed oligoanuria, 22/38 and 3/9 needed dialysis, with hemodialysis used most often in both groups, and plasma infusion(s) were utilized in 6/38 and 4/9 patients, respectively. Of extra-renal complications, neurological complications occurred in 9/38 and 2/9, serious gastrointestinal complications in 6/38 and 1/9, respiratory complications in 10/38 and 2/9, and sepsis in 11/38 and 3/9 cases, respectively. Cardiac complications were seen in two D+HUS cases. In patients where data on follow up ≥1 year after admittance were available, 8/21 and 4/7 had persistent proteinuria and 5/19 and 4/5 had persistent hypertension in the D+HUS and D−HUS group, respectively. Two D+HUS and one D−HUS patient were diagnosed with chronic kidney disease and one D+HUS patient required a renal transplantation. Two D+HUS patients died in the acute phase (death rate; 5 %). Conclusions The HUS cases had a high rate of complications and sequelae, including renal, CNS-related, cardiac, respiratory, serious gastrointestinal complications and sepsis, consistent with other studies. This underlines the importance of attention to extra-renal manifestations in the acute phase and in renal long-term follow-up of HUS patients.
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Affiliation(s)
- Gaute Reier Jenssen
- Department of Infectious Disease Epidemiology, Norwegian Institute of Public Health (Nasjonalt Folkehelseinstitutt), Postboks 4404, Nydalen, NO 0403, Oslo, Norway. .,Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
| | - Line Vold
- Department of Infectious Disease Epidemiology, Norwegian Institute of Public Health (Nasjonalt Folkehelseinstitutt), Postboks 4404, Nydalen, NO 0403, Oslo, Norway
| | - Eirik Hovland
- Department of Infectious Disease Epidemiology, Norwegian Institute of Public Health (Nasjonalt Folkehelseinstitutt), Postboks 4404, Nydalen, NO 0403, Oslo, Norway.,Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | | | - Karin Nygård
- Department of Infectious Disease Epidemiology, Norwegian Institute of Public Health (Nasjonalt Folkehelseinstitutt), Postboks 4404, Nydalen, NO 0403, Oslo, Norway
| | - Anna Bjerre
- Department of Pediatrics, Oslo University Hospital, Oslo, Norway
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20
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Teoh CW, Riedl M, Licht C. The alternative pathway of complement and the thrombotic microangiopathies. Transfus Apher Sci 2016; 54:220-31. [PMID: 27160864 DOI: 10.1016/j.transci.2016.04.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Thrombotic microangiopathies (TMA) are disorders defined by microangiopathic hemolytic anemia, non-immune thrombocytopenia and have multi-organ involvement including the kidneys, brain, gastrointestinal, respiratory tract and skin. Emerging evidence points to the central role of complement dysregulation in leading to microvascular endothelial injury which is crucial for the development of TMAs. This key insight has led to the development of complement-targeted therapy. Eculizumab is an anti-C5 monoclonal antibody, which has revolutionized the treatment of atypical hemolytic uremic syndrome. Several other anti-complement therapeutic agents are currently in development, offering a potential armamentarium of therapies available to treat complement-mediated TMAs. The development of sensitive, reliable and easy to perform assays to monitor complement activity and therapeutic efficacy will be key to devising an individualized treatment regime with the potential of safely weaning or discontinuing treatment in the appropriate clinical setting.
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Affiliation(s)
- Chia Wei Teoh
- Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada; Research Institute, Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Magdalena Riedl
- Research Institute, Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatrics, Innsbruck Medical University, Innsbruck, Austria
| | - Christoph Licht
- Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada; Research Institute, Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
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21
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Woo DE, Lee JM, Kim YK, Park YH. Recombinant Human Erythropoietin Therapy for a Jehovah's Witness Child With Severe Anemia due to Hemolytic-Uremic Syndrome. KOREAN JOURNAL OF PEDIATRICS 2016; 59:100-3. [PMID: 26958070 PMCID: PMC4781730 DOI: 10.3345/kjp.2016.59.2.100] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Revised: 10/02/2014] [Accepted: 10/20/2014] [Indexed: 11/27/2022]
Abstract
Patients with hemolytic-uremic syndrome (HUS) can rapidly develop profound anemia as the disease progresses, as a consequence of red blood cell (RBC) hemolysis and inadequate erythropoietin synthesis. Therefore, RBC transfusion should be considered in HUS patients with severe anemia to avoid cardiac or pulmonary complications. Most patients who are Jehovah's Witnesses refuse blood transfusion, even in the face of life-threatening medical conditions due to their religious convictions. These patients require management alternatives to blood transfusions. Erythropoietin is a glycopeptide that enhances endogenous erythropoiesis in the bone marrow. With the availability of recombinant human erythropoietin (rHuEPO), several authors have reported its successful use in patients refusing blood transfusion. However, the optimal dose and duration of treatment with rHuEPO are not established. We report a case of a 2-year-old boy with diarrhea-associated HUS whose family members are Jehovah's Witnesses. He had severe anemia with acute kidney injury. His lowest hemoglobin level was 3.6 g/dL, but his parents refused treatment with packed RBC transfusion due to their religious beliefs. Therefore, we treated him with high-dose rHuEPO (300 IU/kg/day) as well as folic acid, vitamin B12, and intravenous iron. The hemoglobin level increased steadily to 7.4 g/dL after 10 days of treatment and his renal function improved without any complications. To our knowledge, this is the first case of successful rHuEPO treatment in a Jehovah's Witness child with severe anemia due to HUS.
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Affiliation(s)
- Da Eun Woo
- Department of Pediatrics, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Korea
| | - Jae Min Lee
- Department of Pediatrics, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Korea
| | - Yu Kyung Kim
- Department of Laboratory Medicine, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Korea
| | - Yong Hoon Park
- Department of Pediatrics, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Korea
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22
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Janapatla RP, Hsu MH, Liao WT, Chien KY, Lee HY, Chiu CH. Low Serum Fetuin-A as a Biomarker to Predict Pneumococcal Necrotizing Pneumonia and Hemolytic Uremic Syndrome in Children. Medicine (Baltimore) 2016; 95:e3221. [PMID: 27043691 PMCID: PMC4998552 DOI: 10.1097/md.0000000000003221] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Streptococcus pneumoniae, a neuraminidase-producing pathogen, can cause invasive pneumococcal disease (IPD) with or without hemolytic uremic syndrome (HUS) in humans. We aimed to identify serum sialoglycoproteins that are targeted by neuraminidases in severe pneumococcal infection. We hypothesized that serum sialoglycoprotein such as fetuin-A can serve as a biomarker to predict IPD or HUS. We constructed serum sialoglycoprotein profiles before and after pneumococcal neuraminidase treatment using liquid chromatography-tandem mass spectrometry (LC-MS/MS), a proteomic approach. An observational study was conducted using clinical data and serum samples from pediatric patients with pneumococcal infection to verify the predictive role of fetuin-A in IPD. Serum fetuin-A levels were determined by enzyme-linked immunosorbent assay. The most abundant serum sialoglycoproteins identified by LC-MS/MS after neuraminidase treatment and peanut lectin capture were immunoglobulins, apolipoproteins, fibrinogens, keratins, complement system proteins, and fetuin-A. Serum fetuin-A levels in the HUS patients were significantly lower (207 ± 80 mg/L, P < 0.001) than in patients with lobar pneumonia (610 ± 190 mg/L) as well as the healthy controls (630 ± 250 mg/L). In comparing HUS with necrotizing pneumonia and lobar pneumonia, the ROC area under the curve was 0.842; a cutoff value of 298 mg/L yielded sensitivity of 92.9% (95% CI: 68.5-98.7%) and specificity of 71.9% (95% CI: 54.6-84.4%). This observational study with validation cohorts of patients with HUS, complicated pneumonia, and lobar pneumonia demonstrates the high performance of low serum fetuin-A levels as a biomarker to predict severe IPD and HUS in children.
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Affiliation(s)
- Rajendra Prasad Janapatla
- From the Molecular Infectious Disease Research Center (RPJ, MHH, W-TL, H-YL, C-HC), Chang Gung Memorial Hospital; Graduate Institute of Biomedical Sciences (K-YC, C-HC); and Division of Pediatric Infectious Diseases (H-YL, C-HC), Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
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23
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Affiliation(s)
- T Keefe Davis
- Washington University School of Medicine, St Louis, MO 63110, USA
| | - Paul Hmiel
- Washington University School of Medicine, St Louis, MO 63110, USA
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24
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Davin JC, van de Kar NCAJ. Advances and challenges in the management of complement-mediated thrombotic microangiopathies. Ther Adv Hematol 2015; 6:171-85. [PMID: 26288712 PMCID: PMC4530367 DOI: 10.1177/2040620715577613] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Complement activation plays a major role in several renal pathophysiological conditions. The three pathways of complement lead to C3 activation, followed by the formation of the anaphylatoxin C5a and the terminal membrane attack complex (MAC) in blood and at complement activating surfaces, lead to a cascade of events responsible for inflammation and for the induction of cell lysis. In case of ongoing uncontrolled complement activation, endothelial cells activation takes place, leading to events in which at the end thrombotic microangiopathy can occur. Atypical haemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy characterized by excessive complement activation on the surface of the microcirculation. It is a severe, rare disease which leads to end-stage renal failure (ESRF) and/or to death in more than 50% of patients without treatment. In the first decade of the second millennium, huge progress in understanding the aetiology of this disease was made, which paved the way to better treatment. First, protocols of plasma therapy for treatment, prevention of relapses and for renal transplantation in those patients were set up. Secondly, in some severe cases, combined kidney and liver transplantation was reported. Finally, at the end of this decade, the era of complement inhibitors, as anti-C5 monoclonal antibody (anti-C5 mAb) began. The past five years have seen growing evidence of the favourable effect of anti-C5 mAb in aHUS which has made this drug the first-line treatment in this disease. The possible complication of meningococcal infection needs appropriate vaccination before its use. Unfortunately, the worldwide use of anti-C5 mAb is limited by its very high price. In the future, extension of indications for anti-C5 mAb use, the elaboration of generics and of mAbs directed towards other complement factors of the terminal pathway of the complement system might succeed in reducing the cost of this new valuable therapeutic approach and render it available worldwide for patients from all social classes.
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Affiliation(s)
- Jean-Claude Davin
- Paediatric Nephrology Department, Emma Children's Hospital-Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam Z-O, The Netherlands
| | - Nicole C A J van de Kar
- Department of Paediatric Nephrology, Radboud University Medical Centre, Amalia Children's Hospital, Nijmegen, The Netherlands
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25
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Thévenot J, Cordonnier C, Rougeron A, Le Goff O, Nguyen HTT, Denis S, Alric M, Livrelli V, Blanquet-Diot S. Enterohemorrhagic Escherichia coli infection has donor-dependent effect on human gut microbiota and may be antagonized by probiotic yeast during interaction with Peyer's patches. Appl Microbiol Biotechnol 2015; 99:9097-110. [PMID: 26084888 DOI: 10.1007/s00253-015-6704-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2015] [Revised: 05/13/2015] [Accepted: 05/17/2015] [Indexed: 01/05/2023]
Abstract
Enterohemorrhagic Escherichia coli (EHEC) are major food-borne pathogens responsible for serious infections ranging from mild diarrhea to hemorrhagic colitis and life-threatening complications. Shiga toxins (Stxs) are the main virulence factor of EHEC. The antagonistic effect of a prophylactic treatment with the probiotic strain Saccharomyces cerevisiae against EHEC O157:H7 was investigated using complementary in vitro human colonic model and in vivo murine ileal loop assays. In vitro, the probiotic treatment had no effect on O157:H7 survival but favorably influenced gut microbiota activity through modulation of short-chain fatty acid production, increasing acetate production and decreasing that of butyrate. Both pathogen and probiotic strains had individual-dependent effects on human gut microbiota. For the first time, stx expression was followed in human colonic environment: at 9 and 12 h post EHEC infection, probiotic treatment significantly decreased stx mRNA levels. Besides, in murine ileal loops, the probiotic yeast specifically exerted a trophic effect on intestinal mucosa and inhibited O157:H7 interactions with Peyer's patches and subsequent hemorrhagic lesions. Taken together, the results suggest that S. cerevisiae may be useful in the fight against EHEC infection and that host associated factors such as microbiota could influence clinical evolution of EHEC infection and the effectiveness of probiotics.
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Affiliation(s)
- J Thévenot
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.,Centre de Recherche en Nutrition Humaine Auvergne, M2iSH, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte UMR INSERM / Université d'Auvergne U1071 USC-INRA 2018, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - C Cordonnier
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.,Centre de Recherche en Nutrition Humaine Auvergne, M2iSH, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte UMR INSERM / Université d'Auvergne U1071 USC-INRA 2018, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - A Rougeron
- Centre de Recherche en Nutrition Humaine Auvergne, M2iSH, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte UMR INSERM / Université d'Auvergne U1071 USC-INRA 2018, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - O Le Goff
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - H T T Nguyen
- Centre de Recherche en Nutrition Humaine Auvergne, M2iSH, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte UMR INSERM / Université d'Auvergne U1071 USC-INRA 2018, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - S Denis
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - M Alric
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - V Livrelli
- Centre de Recherche en Nutrition Humaine Auvergne, M2iSH, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte UMR INSERM / Université d'Auvergne U1071 USC-INRA 2018, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.,Service de Bactériologie, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - S Blanquet-Diot
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
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Pape L, Hartmann H, Bange FC, Suerbaum S, Bueltmann E, Ahlenstiel-Grunow T. Eculizumab in Typical Hemolytic Uremic Syndrome (HUS) With Neurological Involvement. Medicine (Baltimore) 2015; 94:e1000. [PMID: 26091445 PMCID: PMC4616562 DOI: 10.1097/md.0000000000001000] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
In typical hemolytic uremic syndrome (HUS) approximately 25% of patients show central nervous system (CNS) involvement often leading to serious long-term disabilities. We used the C5-complement inhibitor Eculizumab as rescue therapy. From 2011 to 2014, 11 children (median age 22 months, range 11-175) with enterohemorrhagic Escherichia coli-positive HUS requiring dialysis who had seizures (11/11) and/or were in a stupor or coma (10/11) were treated with Eculizumab. Two patients enrolled on the Safety and Efficacy Study of Eculizumab in Shiga-Toxin Producing E coli Hemolytic-Uremic Syndrome (STEC-HUS) each received 6 doses of Eculizumab, 3 patients 2 doses, and 6 patients 1 dose. Laboratory diagnostics of blood samples and magnetic resonance imaging (MRI) were performed as per center practice. Data were analyzed retrospectively. Cranial MRI was abnormal in 8 of 10 patients with findings in the basal ganglia and/or white matter. A 2-year-old boy with severe cardiac involvement and status epilepticus needed repeated cardio-pulmonary resuscitation and extracorporeal membrane oxygenation. He died 8 days after start of Eculizumab treatment. Two patients with hemorrhagic colitis and repeated seizures required artificial ventilation for 6 and 16 days, respectively. At the time of discharge, 1 patient showed severe neurological impairment and 1 mild neurological impairment. The 8 surviving patients experienced no further seizures after the first dose of Eculizumab. Three patients showed mild neurological impairment at discharge, whilst the remaining 5 showed no impairment. The platelets normalized 4 days (median) after the first dose of Eculizumab (range 0-20 days). The mean duration of dialysis after the first dose of Eculizumab was 14.1 ± 6.1 days. In children with typical HUS and CNS involvement early use of Eculizumab appears to improve neurological outcome. In severe HUS cases which progress rapidly with multiple organ involvement, late treatment with Eculizumab seems to show less benefit. We speculate that prophylactic Eculizumab therapy before development of neurological symptoms could be advantageous.
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Affiliation(s)
- Lars Pape
- From the Division of Pediatric Nephrology (LP, TA-G); Division of Neuropediatrics, Department of Pediatric Kidney, Liver and Metabolic Diseases (HH); Department of Microbiology (FCB, SS); and Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Hannover, Germany (EB)
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Saini A, Emke AR, Silva MC, Perlman SJ. Response to Eculizumab in Escherichia coli O157: H7-induced hemolytic uremic syndrome with severe neurological manifestations. Clin Pediatr (Phila) 2015; 54:387-9. [PMID: 24817079 DOI: 10.1177/0009922814534520] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Arun Saini
- Division of Critical Care Medicine, Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA
| | - Amanda R Emke
- Division of Critical Care Medicine, Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA
| | - Manuel C Silva
- Division of Critical Care Medicine, Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA
| | - Seth J Perlman
- Division of Neurology and Behavioural Pediatrics, Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, USA
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Buder K, Latal B, Nef S, Neuhaus TJ, Laube GF, Spartà G. Neurodevelopmental long-term outcome in children after hemolytic uremic syndrome. Pediatr Nephrol 2015; 30:503-13. [PMID: 25234636 DOI: 10.1007/s00467-014-2950-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2014] [Revised: 08/22/2014] [Accepted: 08/25/2014] [Indexed: 02/01/2023]
Abstract
BACKGROUND To investigate the long-term neurodevelopmental outcome in children after hemolytic uremic syndrome (HUS) and to compare outcome dependent on central nervous system (CNS) involvement during HUS. METHODS A single-center retrospective cohort of 47 children was examined at a median age of 10.6 (range 6-16.9) years and a median follow-up of 7.8 (range 0.4-15.3) years after having had HUS. Intellectual performance was assessed with the German version of the Wechsler Intelligence Scale 4th version and neuromotor performance with the Zurich Neuromotor Assessment (ZNA). The occurrence of neurological symptoms during the acute phase of HUS was evaluated retrospectively. RESULTS Mean IQ of the whole study population fell within the normal range (median full scale IQ 104, range 54-127). Neuromotor performance was significantly poorer in the domains "adaptive fine," "gross motor," "static balance" (all p < 0.05) and "associated movements" (p < 0.001); only the "pure motor" domain was within the normal reference range. Neurological findings occurred in 16/47 patients (34 %) during acute HUS. Neurodevelopmental outcome was not significantly different between children with or without CNS involvement. CONCLUSIONS Our follow-up of children after HUS showed a favorable cognitive outcome. However, neuromotor outcome was impaired in all study participants. Neurological impairment during acute HUS was not predictive of outcome.
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Affiliation(s)
- Kathrin Buder
- Pediatric Nephrology Unit, University Children's Hospital, Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland
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Balestracci A, Martin SM, Toledo I, Alvarado C, Wainsztein RE. Early erythropoietin in post-diarrheal hemolytic uremic syndrome: a case-control study. Pediatr Nephrol 2015; 30:339-44. [PMID: 25138373 DOI: 10.1007/s00467-014-2911-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2014] [Revised: 07/01/2014] [Accepted: 07/10/2014] [Indexed: 12/25/2022]
Abstract
BACKGROUND Although erythropoietin (EPO) deficiency has been reported in children with post-diarrheal hemolytic uremic syndrome (D + HUS), very limited clinical data on EPO use in this disease are currently available. In this case-control study we examined whether EPO administration would reduce the number of red blood cell (RBC) transfusions in D + HUS patients under our care. METHODS Data from children treated exclusively with RBC transfusions (controls; n = 21) were retrospectively compared with data on those who also received EPO for the treatment of anemia (cases; n = 21). RESULTS Both patient groups were similar in age (p = 0.9), gender (p = 0.12), weight (p = 1.00) and height (p = 0.66). Acute phase severity was also comparable, as inferred by the need for dialysis (p = 0.74), the duration of dialysis (p = 0.3), length of hospitalization (p = 0.81), presence of severe bowel (p = 1.00) or neurological injury (p = 0.69), arterial hypertension (p = 1.00) and death (p = 1.00). No differences in the hemoglobin level at admission (p = 0.51) and discharge (p = 0.28) were noted. Three children treated with EPO and two controls did not require any RBC transfusion (p = 1.00). Median number of RBC transfusions needed by cases and controls was 2 (p = 0.52). CONCLUSION Treatment with EPO did not reduce the number of RBC transfusions in D + HUS children. Assessment of EPO efficacy in D + HUS merits further studies.
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Affiliation(s)
- Alejandro Balestracci
- Unidad de Nefrología, Hospital General de Niños Pedro de Elizalde, Montes de Oca 40, CP 1270, Buenos Aires, Argentina,
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30
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Spezifische Infektionen. DIE INTENSIVMEDIZIN 2015. [PMCID: PMC7123516 DOI: 10.1007/978-3-642-54953-3_74] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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Rusai K, Gruber K, Dufek S, Seidl R, Arbeiter K, Aufricht C, Mueller-Sacherer T. Late-onset neurological symptoms in a child with diarrhea-associated hemolytic uremic syndrome. Ther Apher Dial 2014; 19:192-4. [PMID: 25363791 DOI: 10.1111/1744-9987.12243] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Krisztina Rusai
- Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Vienna, Austria.
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Keir LS, Saleem MA. Current evidence for the role of complement in the pathogenesis of Shiga toxin haemolytic uraemic syndrome. Pediatr Nephrol 2014; 29:1895-902. [PMID: 23843163 DOI: 10.1007/s00467-013-2561-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2012] [Revised: 05/21/2013] [Accepted: 06/21/2013] [Indexed: 12/30/2022]
Abstract
Shiga toxin-associated haemolytic uraemic syndrome (Stx HUS) is the leading cause of paediatric acute kidney injury. This toxin-mediated disease carries a significant morbidity and mortality but has no direct treatments. Rare familial atypical HUS (aHUS) is now understood to result from over-activation of the alternative complement pathway causing glomerular endothelial damage. By understanding the pathogenic mechanisms of this disease, the monoclonal antibody eculizumab, which blocks the final common pathway of complement, is now being used to treat aHUS. For this reason, clinicians and scientists are studying the role of the alternative complement pathway in Stx HUS with the aim of targeting treatment in a similar way. There is some evidence suggesting that complement plays a role in the pathogenesis of Stx HUS, but other mechanisms may also be important. Clinically, modulating the complement system using plasma exchange provides no proven benefit in Stx HUS, and the use of eculizumab has provided conflicting results. Understanding the local effect of Stx on the glomerulus, in particular regulation of the complement and coagulation systems, may lead to advances in defining the precise pathogenesis of this disease. Then, targeted treatment strategies could be devised and clinical trials undertaken.
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Affiliation(s)
- Lindsay S Keir
- Academic Renal Unit, University of Bristol-Southmead Hospital, Bristol, UK,
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Bauer A, Loos S, Wehrmann C, Horstmann D, Donnerstag F, Lemke J, Hillebrand G, Löbel U, Pape L, Haffner D, Bindt C, Ahlenstiel T, Melk A, Lehnhardt A, Kemper MJ, Oh J, Hartmann H. Neurological involvement in children with E. coli O104:H4-induced hemolytic uremic syndrome. Pediatr Nephrol 2014; 29:1607-15. [PMID: 24664191 DOI: 10.1007/s00467-014-2803-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2014] [Revised: 02/27/2014] [Accepted: 02/28/2014] [Indexed: 11/25/2022]
Abstract
BACKGROUND The aim of this study was to analyze the neurological involvement and outcome in pediatric patients with hemolytic uremic syndrome (HUS) during the 2011 epidemic caused by Escherichia coli O104:H4. METHODS Clinical data and data from magnetic resonance imaging (MRI) scans and electroencephalography (EEG) during the acute phase of the disease and during follow-up at 3 and 6 months were analyzed in 50 patients. Twenty-five of these patients underwent neuropsychological testing (WISC IV) during follow-up. RESULTS Neurological involvement (stupor or coma, seizures, visual disturbances, paresis, myocloni) was initially observed in 14/50 (28%) patients. One patient died. EEG abnormalities were more frequent in patients with neurological involvement than in those without (12/14 vs. 13/25, respectively). Cranial MRI scans were analyzed in nine patients with neurological involvement, of whom five showed abnormal findings. At the 3- and 6-month follow-ups, EEG abnormalities were found in 14/40 (35%) and 7/36 (19%) patients, respectively, whereas 28/42 (67%) and 17/39 (44%) patients, respectively, complained about on-going reduced performance. Neuropsychological testing showed a slightly lower global intelligence quotient in patients with neurological involvement versus those without (113.4 ± 2.8 vs. 119.4 ± 1.8, respectively). CONCLUSIONS Neurological involvement was frequent in our cohort. Accordingly, the incidence of pathological EEG findings was high, even in patients without clinical signs of neurological involvement. Nevertheless, major neurological sequelae were rare, and neuropsychological outcome was favorable after 6 months.
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Affiliation(s)
- Angela Bauer
- Department of Pediatrics, University Medical Center Hamburg, Hamburg, Germany
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Detection and Characterization of Shiga Toxin Producing Escherichia coli, Salmonella spp., and Yersinia Strains from Human, Animal, and Food Samples in San Luis, Argentina. Int J Microbiol 2014; 2014:284649. [PMID: 25177351 PMCID: PMC4142171 DOI: 10.1155/2014/284649] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2014] [Revised: 05/24/2014] [Accepted: 07/14/2014] [Indexed: 11/18/2022] Open
Abstract
Shiga toxin producing Escherichia coli (STEC), Salmonella spp., and Yersinia species was investigated in humans, animals, and foods in San Luis, Argentina. A total of 453 samples were analyzed by culture and PCR. The antimicrobial susceptibility of all the strains was studied, the genomic relationships among isolates of the same species were determined by PFGE, and the potencial virulence of Y. enterocolitica strains was analyzed. Yersinia species showed higher prevalence (9/453, 2.0%, 95% CI, 0.7–3.3%) than STEC (4/453, 0.9%, 95% CI, 0–1.8%) and Salmonella spp. (3/453, 0.7%, 95% CI, 0–1.5%). Y. enterocolitica and Y. intermedia were isolated from chicken carcasses (6/80, 7.5%, 95% CI, 1.5–13.5%) and porcine skin and bones (3/10, 30%, 95% CI, 0–65%). One STEC strain was recovered from human feces (1/70, 1.4%, 95% CI, 0–4.2%) and STEC stx1/stx2 genes were detected in bovine stools (3/129, 2.3%, 95% CI, 0–5.0%). S. Typhimurium was isolated from human feces (1/70, 1.4%, 95% CI, 0–4.2%) while one S. Newport and two S. Gaminara strains were recovered from one wild boar (1/3, 33%, 95% CI, 0–99%). The knowledge of prevalence and characteristics of these enteropathogens in our region would allow public health services to take adequate preventive measures.
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da Silva PSL, Lipinski RW. Hemolytic uremic syndrome associated withAcinetobacter hemolyticus. Ren Fail 2014; 36:1122-4. [DOI: 10.3109/0886022x.2014.917575] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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36
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Shigella Species. Food Microbiol 2014. [DOI: 10.1128/9781555818463.ch15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Cocaine-associated retiform purpura: a C5b-9-mediated microangiopathy syndrome associated with enhanced apoptosis and high levels of intercellular adhesion molecule-1 expression. Am J Dermatopathol 2014; 35:722-30. [PMID: 23392134 DOI: 10.1097/dad.0b013e31827eaf0b] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Cocaine-associated retiform purpura is a recently described entity characterized by striking hemorrhagic necrosis involving areas of skin associated with administration of cocaine. Levamisole, an adulterant in cocaine, has been suggested as the main culprit pathogenetically. Four cases of cocaine-associated retiform purpura were encountered in the dermatopathology practice of C. M. Magro. The light microscopic findings were correlated with immunohistochemical and immunofluorescence studies. All 4 cases showed a very striking thrombotic diathesis associated with intravascular macrophage accumulation. Necrotizing vasculitis was noted in 1 case. Striking intercellular adhesion molecule-1 (ICAM-1)/CD54 expression in vessel wall along with endothelial expression of caspase 3 and extensive vascular C5b-9 deposition was observed in all biopsies examined. Cocaine-induced retiform purpura is a C5b-9-mediated microvascular injury associated with enhanced apoptosis and prominent vascular expression of ICAM-1, all of which have been shown in prior in vitro and in vivo murine models to be a direct effect of cocaine metabolic products. Antineutrophilic cytoplasmic antibody and antiphospholipid antibodies are likely the direct sequelae of the proapoptotic microenvironment. The inflammatory vasculitic lesion could reflect the downstream end point reflective of enhanced ICAM-1 expression and the development of antineutrophilic cytoplasmic antibody. Levamisole likely works synergistically with cocaine in the propagation of this syndromic complex.
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Balestracci A, Martin SM, Toledo I, Alvarado C, Wainsztein RE. Laboratory predictors of acute dialysis in hemolytic uremic syndrome. Pediatr Int 2014; 56:234-9. [PMID: 24266872 DOI: 10.1111/ped.12245] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2013] [Revised: 08/03/2013] [Accepted: 10/24/2013] [Indexed: 11/30/2022]
Abstract
BACKGROUND Strict guidelines on use of dialysis in children with post-diarrheal hemolytic uremic syndrome (D + HUS) are lacking. This study investigated laboratory predictors of acute dialysis because they are more objective than clinical features. Added to this, given that urine output is also an objective parameter, its ability to predict dialysis requirements was also investigated. METHODS Out of 153 D + HUS children reviewed, 88 received dialysis and 65 did not. Initial laboratory parameters and diuresis between both groups were analyzed. RESULTS Dialyzed patients had higher creatinine, urea, alanine aminotransferase, hematocrit and leukocyte count; and lower sodium, bicarbonate, and pH compared to non-dialyzed ones. Serum creatinine was the only independent predictor (P = 0.003) of dialysis; therefore, its ability to predict dialysis was estimated on receiver operating characteristic (ROC) curve analysis and using the Acute Kidney Injury Network (AKIN) staging system. Area under the ROC curve was 0.92 (95% confidence interval [95%CI]: 0.83-1) with a creatinine cut-off of 1.25 mg/dL (sensitivity, 100%; specificity, 76.5%) for children <1 year, and 0.93 (95%CI: 0.88-0.98) with a threshold of 2 mg/dL (sensitivity, 91%; specificity, 87.5%) for older children. AKIN stage 3 at admission predicted dialysis with a sensitivity of 92% and specificity of 84.2%. Urine output had the highest accuracy for dialysis prediction (sensitivity, 100%; specificity, 95.3%). CONCLUSIONS Initial serum creatinine concentration was the best laboratory predictor of dialysis, but the first 24 h diuresis was even better for this purpose. But, given that serum creatinine is an immediate available parameter, the cut-offs identified may label D + HUS children who will probably need dialysis, prompting early referral to centers able to provide dialysis.
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Affiliation(s)
- Alejandro Balestracci
- Nephrology Unit, Pedro de Elizalde Children's Hospital, Buenos Aires City, Argentina
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Ardissino G, Testa S, Possenti I, Tel F, Paglialonga F, Salardi S, Tedeschi S, Belingheri M, Cugno M. Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases. Am J Kidney Dis 2014; 64:633-7. [PMID: 24656451 DOI: 10.1053/j.ajkd.2014.01.434] [Citation(s) in RCA: 153] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Accepted: 01/14/2014] [Indexed: 02/07/2023]
Abstract
Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy, and as many as 70% of patients with aHUS have mutations in the genes encoding complement regulatory proteins. Eculizumab, a humanized recombinant monoclonal antibody targeting C5, has been used successfully in patients with aHUS since 2009. The standard maintenance treatment requires life-long eculizumab therapy, but the possibility of discontinuation has not yet been tested systematically. We report the safety of discontinuing eculizumab treatment in 10 patients who stopped treatment with the aim of minimizing the risk of adverse reactions, reducing the risk of meningitis, and improving quality of life while also reducing the considerable treatment costs. Disease activity was monitored closely at home by means of urine dipstick testing for hemoglobin. During the cumulative observation period of 95 months, 3 of the 10 patients experienced relapse within 6 weeks of discontinuation, but then immediately resumed treatment and completely recovered. Our experience supports the possibility of discontinuing eculizumab therapy with strict home monitoring for early signs of relapse in patients with aHUS who achieve stable remission.
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Affiliation(s)
- Gianluigi Ardissino
- Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
| | - Sara Testa
- Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Ilaria Possenti
- Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Francesca Tel
- Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Fabio Paglialonga
- Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Stefania Salardi
- Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Silvana Tedeschi
- Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Mirco Belingheri
- Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Massimo Cugno
- Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
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Koppula S, Yost SE, Sussman A, Bracamonte ER, Kaplan B. Successful conversion to belatacept after thrombotic microangiopathy in kidney transplant patients. Clin Transplant 2014; 27:591-7. [PMID: 23923969 DOI: 10.1111/ctr.12170] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/14/2013] [Indexed: 12/11/2022]
Abstract
Thrombotic microangiopathy (TMA) is a severe complication of kidney transplantation. TMA may occur de novo or as recurrent disease post-transplant. De novo disease is usually associated with immunosuppressive drugs or can be seen as a part of endothelial damage that accompanies antibody-mediated rejection. Treatment for de novo TMA is limited to plasma exchange and change in immunosuppression. We report two cases of de novo TMA post-transplant that were successfully treated by converting to belatacept for maintenance immunosuppression.
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Affiliation(s)
- Sireesha Koppula
- Department of Nephrology, University of Arizona College of Medicine, Tucson, AZ 85724, USA
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Bernedo-Navarro RA, Miyachiro MM, da Silva MJ, Reis CF, Conceição RA, Gatti MSV, Yano T. Peptides derived from phage display libraries as potential neutralizers of Shiga toxin-induced cytotoxicity in vitro and in vivo. J Appl Microbiol 2014; 116:1322-33. [PMID: 24447276 DOI: 10.1111/jam.12451] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2013] [Revised: 12/21/2013] [Accepted: 01/10/2014] [Indexed: 11/30/2022]
Abstract
AIMS To use the phage display technique to develop peptides with the capability to neutralize the cytotoxicity induced by Stx1 and Stx2 toxins produced by Shiga toxin-producing Escherichia coli (STEC). METHODS AND RESULTS The phage display technique permitted the development of three peptides, named PC7-12, P12-26 and PC7-30, which bind to the globotriaosylceramide (Gb3) receptor for Shiga toxins produced by STEC. Moreover, these peptides were capable of competing efficiently with the Shiga toxins for binding to Gb3. The peptides described herein partially inhibited the Stx-induced cytotoxicity of cell-free filtrates of STEC O157 : H7 and purified Stx toxins in Vero cells. The inhibition of lethality induced by Stx toxins in mice indicated that peptide PC7-30 inhibited the lethality caused by Stx1 (2LD50) in mice. CONCLUSIONS The phage display technique permitted the development of peptides that inhibited the cytotoxicity induced by Stx toxins in vitro. Peptide PC7-30 inhibited the lethality of Stx1 in vivo; this molecule would be a promising candidate for the development of therapeutic agents for STEC-related diseases in humans. SIGNIFICANCE AND IMPACT OF THE STUDY The selection of Gb3, the common receptor for Stx1 and Stx2, may contribute to the development of efficient neutralizers for both toxins, and our approach would be an interesting alternative for the development of therapeutic molecules for the treatment of diseases caused by STEC strains.
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Affiliation(s)
- R A Bernedo-Navarro
- Departamento de Genética, Evolução e Bioagentes, Instituto de Biologia-UNICAMP, Campinas, SP, Brazil
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Büyükçelik M, Keskin M, Keskin Ö, Bay A, Demircioğlu Kılıç B, Kor Y, Kılınç MA, Balat A. Autoimmune polyglandular syndrome type 3c with ectodermal dysplasia, immune deficiency and hemolytic-uremic syndrome. J Clin Res Pediatr Endocrinol 2014; 6:47-50. [PMID: 24637310 PMCID: PMC3986739 DOI: 10.4274/jcrpe.1128] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Autoimmune polyglandular syndrome (APS) is a disorder which is associated with multiple endocrine gland insufficiency and also with non-endocrine manifestations. The pathophysiology of APS is poorly understood, but the hallmark evidence of APS is development of autoantibodies against multiple endocrine and non-endocrine organs. These autoantibodies are responsible for the dysfunction of the affected organs and sometimes may also cause non-endocrine organ dysfunction. The hemolytic-uremic syndrome (HUS) is a serious and life-threatening disease which develops due to many etiological factors including autoimmune disorders. Here, we present an unusual case of APS. Ectodermal dysplasia with immune deficiency and HUS occurred concomitantly in the same patient with APS type 3c. Once the autoantibody generation was initiated in the human body, development of multiple disorders due to organ dysfunction and also autoantibody-related diseases may have occurred.
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Affiliation(s)
- Mithat Büyükçelik
- Gaziantep University Faculty of Medicine, Department of Pediatric Endocrinology and Metabolism, Gaziantep, Turkey. E-mail:
| | - Mehmet Keskin
- Gaziantep University Faculty of Medicine, Department of Pediatric Endocrinology and Metabolism, Gaziantep, Turkey
,* Address for Correspondence: Gaziantep University Faculty of Medicine, Department of Pediatric Endocrinology and Metabolism, Gaziantep, Turkey Phone: +90 342 360 60 60 E-mail:
| | - Özlem Keskin
- Gaziantep University Faculty of Medicine, Department of Pediatric Allergy and Immunology, Gaziantep, Turkey
| | - Ali Bay
- Gaziantep University Faculty of Medicine, Department of Pediatric Hematology, Gaziantep, Turkey
| | | | - Yılmaz Kor
- Gaziantep University Faculty of Medicine, Department of Pediatric Endocrinology and Metabolism, Gaziantep, Turkey
| | - M. Arda Kılınç
- Gaziantep University Faculty of Medicine, Department of Pediatrics, Gaziantep, Turkey
| | - Ayşe Balat
- Gaziantep University Faculty of Medicine, Department of Pediatric Nephrology, Gaziantep, Turkey
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Avcı Z, Bayram C, Malbora B. Hepatitis B vaccine-associated atypical hemolytic uremic syndrome. Turk J Haematol 2014; 30:418-9. [PMID: 24385836 PMCID: PMC3874978 DOI: 10.4274/tjh-2013.0226] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2013] [Accepted: 07/19/2013] [Indexed: 12/01/2022] Open
Affiliation(s)
- Zekai Avcı
- Ankara Children's Hematology and Oncology Research Hospital, Department of Hematology, Ankara, Turkey
| | - Cengiz Bayram
- Ankara Pediatric and Pediatric Hematology Oncology Training and Research Hospital, Department of Pediatric Hematology, Ankara, Turkey
| | - Barış Malbora
- Dr. Sami Ulus Research and Training Hospital of Women's and Children's Health and Diseases, Ankara, Turkey
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Abstract
The thrombotic microangiopathies include both hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Although debate exists as to whether these are separate entities or a spectrum of disease, both result in the clinical picture of thrombocytopenia, hemolytic anemia, and varying degrees of renal and neurologic involvement. Etiology of HUS includes diarrheal infection due to Shiga toxin-producing bacteria, complement deficiency, pneumococcal infection, and cobalamin deficiency. In disease ascribed to TTP, the main etiologic factor is deficiency of an enzyme known as a disintegrin-like and metalloprotease with thrombospondin type 1 repeats, number 13 (ADAMTS-13). The clinical manifestations may vary, but neurologic involvement can be significant, with reports of hypertensive encephalopathy, seizures, thrombosis and infarct. In nondiarrheal forms of disease, recurrence may occur and clinical diagnosis is essential in order to provide a targeted therapy for the suspected etiology. Therapies include supportive care, cobalamin supplementation, as well as plasma infusion and exchange. End stage renal disease may result and transplantation is curative for some forms of the disease. More recent research focuses on targeted immunotherapy to prevent autoantibody prevention. As of yet, there is no one cure for these potentially devastating diseases, and diagnosis and treatment selection presents a challenge to the clinician.
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Affiliation(s)
- Kathleen Webster
- Department of Pediatrics, Loyola University Medical Center, Maywood, IL, USA.
| | - Eugene Schnitzler
- Department of Neurology, Loyola University Medical Center, Maywood, IL, USA
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46
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Bolton-Maggs P. Diagnosis and management of thrombotic microangiopathy: the role of registries. Pediatr Blood Cancer 2013; 60:1561-2. [PMID: 23801568 DOI: 10.1002/pbc.24650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2013] [Accepted: 05/22/2013] [Indexed: 11/08/2022]
Affiliation(s)
- Paula Bolton-Maggs
- Manchester Blood Centre and the University of Manchester, Manchester, UK.
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47
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Salvadori M, Bertoni E. Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations. World J Nephrol 2013; 2:56-76. [PMID: 24255888 PMCID: PMC3832913 DOI: 10.5527/wjn.v2.i3.56] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Revised: 06/26/2013] [Accepted: 08/02/2013] [Indexed: 02/06/2023] Open
Abstract
Hemolytic uremic syndrome (HUS) is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and pathogenetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the complement proteins are clearly involved in all types of thrombotic microangiopathy: typical HUS, atypical HUS and thrombotic thrombocytopenic purpura (TTP). Furthermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic aspects of this rare disease, examining both "traditional therapy" (including plasma therapy, kidney and kidney-liver transplantation) and "new therapies". The latter include anti-Shiga-toxin antibodies and anti-C5 monoclonal antibody "eculizumab". Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases I and II. They include anti-C5 antibodies, which are more purified, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy.
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Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, Bingham C, Cohen DJ, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman RR, Gaber O, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nürnberger J, Ogawa M, Remuzzi G, Richard T, Sberro-Soussan R, Severino B, Sheerin NS, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 2013; 368:2169-81. [PMID: 23738544 DOI: 10.1056/nejmoa1208981] [Citation(s) in RCA: 1100] [Impact Index Per Article: 91.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. METHODS We conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event-free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2). RESULTS A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73×10(9) per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event-free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period. CONCLUSIONS Eculizumab inhibited complement-mediated thrombotic microangiopathy and was associated with significant time-dependent improvement in renal function in patients with atypical hemolytic-uremic syndrome. (Funded by Alexion Pharmaceuticals; C08-002 ClinicalTrials.gov numbers, NCT00844545 [adults] and NCT00844844 [adolescents]; C08-003 ClinicalTrials.gov numbers, NCT00838513 [adults] and NCT00844428 [adolescents]).
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Affiliation(s)
- C M Legendre
- Université Paris Descartes and Assistance Publique–Hôpitaux de Paris, Hôpital Necker, INSERM Unité 845, Paris, France.
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Impact of platelet transfusions in children with post-diarrheal hemolytic uremic syndrome. Pediatr Nephrol 2013; 28:919-25. [PMID: 23386110 DOI: 10.1007/s00467-013-2414-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2012] [Revised: 01/06/2013] [Accepted: 01/07/2013] [Indexed: 10/27/2022]
Abstract
BACKGROUND Platelet transfusions should be avoided in children with post-diarrheal hemolytic uremic syndrome (D + HUS) because they might increase microthrombi formation, thereby aggravating the disease. As this possibility has not yet been explored, we investigated whether platelet transfusion in patients with D + HUS would lead to a worse disease course compared to that in patients who did not receive platelet transfusion. METHODS This was a case-control study in which data from D + HUS children who received platelet transfusions (cases, n = 23) and those who did not (controls, n = 54) were retrospectively reviewed and compared. RESULTS Both patient groups were similar in age (p = 0.3), gender (p = 0.53), weight (p = 0.86), height (p = 0.45), prior use of non-steroidal anti-inflammatory drugs (p = 0.59) or antibiotics (p = 0.45) and presence of dehydration at admission (p = 0.79). The two groups also did not differ in initial leukocyte count (p = 0.98), hematocrit (p = 0.44) and sodium (p = 0.11) and alanine aminotransferase levels (p = 0.11). During hospitalization, dialysis duration (p = 0.08), number of erythrocyte transfusions (p = 0.2), serum creatinine peak (p = 0.22), presence of severe bowel (p = 0.43) or neurologic (p = 0.97) injury, arterial hypertension (p = 0.71), need for intensive care (p = 0.33) and death (p = 1.00) were also comparable. CONCLUSION Our findings suggest that platelet transfusion does not aggravate the course of the disease. Conversely, no hemorrhagic complications were observed in the group of patients who did not receive a platelet transfusion. Until these observations are confirmed by further studies, the benefits and risk of platelet transfusion should be thoughtfully balanced on an individual case basis.
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Tracking sickness through social networks - the practical use of social network mapping in supporting the management of an E. coli O157 outbreak in a primary school in London. Epidemiol Infect 2013; 141:2022-30. [PMID: 23445786 PMCID: PMC3757920 DOI: 10.1017/s0950268813000344] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
This paper describes the practical use of social network diagrams in the management of an outbreak of Escherichia coli O157 (VTEC) in a primary school in London. The diagrams were created during the outbreak to establish the extent and nature of person-to-person transmission in the cases and their contacts. The diagrams supported a tailored public health action, and hence aided in the control of the outbreak. We conclude that for selected infectious diseases, social network diagrams can provide a valuable tool in the management of an outbreak.
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