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The American Journal of Case Reports Feb 2015Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by hemolysis, thrombocytopenia, and renal dysfunction. It is a disease related to genetic... (Review)
Review
BACKGROUND
Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by hemolysis, thrombocytopenia, and renal dysfunction. It is a disease related to genetic mutations in the alternative complement pathway and has a distinct pathophysiology but is difficult to differentiate from other thrombotic microangiopathies.
CASE REPORT
We present a case of a 59-year-old female patient who presented with accelerated hypertension, acute renal failure, hemolysis, and encephalopathy. She was managed with antihypertensive medication, but her encephalopathy did not improve. Evaluation resulted in our impression of the disease being atypical hemolytic-uremic syndrome. The patient continued to be managed with good blood pressure control and later was started on eculizumab, but evaluation of response to therapy was hindered by the patient's non-compliance with therapy and follow-up appointments.
CONCLUSIONS
We have a very limited understanding of the genetics and epidemiology of atypical HUS, and the overlapping clinical features sometimes delay diagnosis and initiation of appropriate treatment of this rare disease.
Topics: Algorithms; Atypical Hemolytic Uremic Syndrome; Diagnosis, Differential; Female; Humans; Middle Aged; Prognosis
PubMed: 25708146
DOI: 10.12659/AJCR.892907 -
Asian Journal of Surgery Feb 2023
Topics: Humans; Hemolytic-Uremic Syndrome; Diagnosis, Differential
PubMed: 35963672
DOI: 10.1016/j.asjsur.2022.07.055 -
Revista Medica de Chile Jun 2018Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy, characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal... (Review)
Review
Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy, characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal involvement. It causes end stage renal disease requiring dialysis in most affected patients. It mainly affects young adults (contrary to what was thought years ago). When aHUS is primary, the cause is a genetic mutation in the alternative complement pathway. Instead, secondary aHUS is caused by external factors that trigger the disease by themselves or in combination with a genetic vulnerability. The type of mutation determines the severity of the disease, prognosis, response to therapy and renal transplantation. Advances in the understanding of renal diseases associated with complement defects and the development of specific biologic therapies changed the course of this disease. Eculizumab is internationally approved for the treatment of primary aHUS. Its inhibitory action on the complement cascade leads to hematologic remission and restoration of renal function. We present a review of aHUS detailing its etiology, pathogenesis, clinical presentation, diagnosis and treatment.
Topics: Antibodies, Monoclonal, Humanized; Atypical Hemolytic Uremic Syndrome; Humans; Kidney Transplantation; Mutation
PubMed: 30148909
DOI: 10.4067/s0034-98872018000600770 -
Pediatric Nephrology (Berlin, Germany) Oct 2008Hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in childhood and the reason for chronic renal replacement therapy. It leads to... (Review)
Review
Hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in childhood and the reason for chronic renal replacement therapy. It leads to significant morbidity and mortality during the acute phase. In addition to acute morbidity and mortality, long-term renal and extrarenal complications can occur in a substantial number of children years after the acute episode of HUS. The most common infectious agents causing HUS are enterohemorrhagic Escherichia coli (EHEC)-producing Shiga toxin (and belonging to the serotype O157:H7) and several non-O157:H7 serotypes. D(+) HUS is an acute disease characterized by prodromal diarrhea followed by acute renal failure. The classic clinical features of HUS include the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. HUS mortality is reported to be between 3% and 5%, and death due to HUS is nearly always associated with severe extrarenal disease, including severe central nervous system (CNS) involvement. Approximately two thirds of children with HUS require dialysis therapy, and about one third have milder renal involvement without the need for dialysis therapy. General management of acute renal failure includes appropriate fluid and electrolyte management, antihypertensive therapy if necessary, and initiation of renal replacement therapy when appropriate. The prognosis of HUS depends on several contributing factors. In general "classic" HUS, induced by EHEC, has an overall better outcome. Totally different is the prognosis in patients with atypical and particularly recurrent HUS. However, patients with severe disease should be screened for genetic disorders of the complement system or other underlying diseases.
Topics: Anti-Bacterial Agents; Hemolytic-Uremic Syndrome; Humans; Prognosis; Renal Dialysis; Shiga Toxin
PubMed: 18704506
DOI: 10.1007/s00467-008-0935-6 -
Nephron. Clinical Practice 2010Atypical hemolytic uremic syndrome (aHUS) is a rare disease of microangiopathic hemolytic anemia, thrombocytopenia, and predominant renal impairment. It is characterized... (Review)
Review
Atypical hemolytic uremic syndrome (aHUS) is a rare disease of microangiopathic hemolytic anemia, thrombocytopenia, and predominant renal impairment. It is characterized by the absence of Shiga toxin-producing bacteria as a triggering factor. During the last decade, aHUS has been demonstrated to be a disorder of the complement alternative pathway dysregulation, as there is a growing list of mutations and polymorphisms in the genes encoding the complement regulatory proteins that alone or in combination may lead to aHUS. Approximately 60% of aHUS patients have so-called 'loss-of-function' mutations in the genes encoding the complement regulatory proteins, which normally protect host cells from complement activation: complement factor H (CFH), factor I (CFI) and membrane cofactor protein (MCP or CD46), or have 'gain-of-function' mutations in the genes encoding the complement factor B or C3. In addition, approximately 10% of aHUS patients have a functional CFH deficiency due to anti-CFH antibodies. Recent advances in understanding the pathogenesis of aHUS have led to a revised classification of the syndrome. Normal plasma levels of CFH and CFI do not preclude the presence of a mutation in these genes. Further, genotype-phenotype correlations of aHUS have clinical significance in predicting renal recovery and transplant outcome. Therefore, it is important to make a comprehensive analysis and perform genetic screening of the complement system in patients with aHUS to allow a more precise approach, especially before transplantation. This may also provide opportunities for more specific treatments in the near future, as complement inhibition could represent a therapeutic target in these patients who have a considerably poor prognosis in terms of both mortality and progression to end-stage renal disease and a great risk of disease recurrence after transplantation.
Topics: Animals; Complement Activation; Complement System Proteins; Hemolytic-Uremic Syndrome; Humans; Mutation; Plasma Exchange; Stem Cell Transplantation
PubMed: 20090363
DOI: 10.1159/000276545 -
Clinical & Developmental Immunology 2012Atypical hemolytic uremic syndrome (aHUS) is a rare renal disease (two per one million in the USA) characterized by microangiopathic hemolytic anemia, thrombocytopenia,... (Review)
Review
Atypical hemolytic uremic syndrome (aHUS) is a rare renal disease (two per one million in the USA) characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Both sporadic (80% of cases) and familial (20% of cases) forms are recognized. The study of familial aHUS has implicated genetic variation in multiple genes in the complement system in disease pathogenesis, helping to define the mechanism whereby complement dysregulation at the cell surface level leads to both sporadic and familial disease. This understanding has culminated in the use of Eculizumab as first-line therapy in disease treatment, significantly changing the care and prognosis of affected patients. However, even with this bright outlook, major challenges remain to understand the complexity of aHUS at the genetic level. It is possible that a more detailed picture of aHUS can be translated to an improved understanding of disease penetrance, which is highly variable, and response to therapy, both in the short and long terms.
Topics: Atypical Hemolytic Uremic Syndrome; Complement System Proteins; Genetic Variation; Hemolytic-Uremic Syndrome; Humans
PubMed: 23251215
DOI: 10.1155/2012/370426 -
Archivos Argentinos de Pediatria Aug 2021The usual definition of Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) is based on the presence of anemia, thrombocytopenia, and elevated...
INTRODUCTION
The usual definition of Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) is based on the presence of anemia, thrombocytopenia, and elevated serum creatinine levels, with or without proteinuria and/or hematuria. The strict definition only considers elevated serum creatinine levels as a renal criterion. The extended definition maintains flexible renal criteria, although it replaces anemia with hemolysis and considers a sharp drop in platelet count as an indicator of platelet consumption. The objective of this study was to estimate and compare the diagnostic sensitivity of these definitions in patients with STEC-HUS as hospital discharge diagnosis.
POPULATION AND METHODS
Retrospective review of medical records of HUS patients. Sensitivity and positive predictive value, with their corresponding 95% confidence intervals (CIs), were estimated for the 3 definitions based on a discharge diagnosis of STEC-HUS (reference diagnosis). The McNemar test was used.
RESULTS
Out of 208 patients, 107 (51.4%), 133 (63.9%), and 199 (95.6%) were identified with the strict, usual, and extended definition, respectively. Sensitivity was lower for the strict definition (51.4%; 95% CI: 44.8-58.3), intermediate for the usual definition (63.9%; 95% CI: 56.9-70.4), and higher for the extended one (95.6%; 95% CI: 91.6-97.8); (p< 0.001).
CONCLUSION
The different STEC-HUS definitions showed significant differences in diagnostic sensitivity. The extended definition reached a sensitivity above 95%, so its generalized use may help to reduce diagnostic delays.
Topics: Escherichia coli Infections; Hemolytic-Uremic Syndrome; Humans; Retrospective Studies; Shiga-Toxigenic Escherichia coli
PubMed: 34309299
DOI: 10.5546/aap.2021.eng.238 -
Journal of Internal Medicine Feb 2017Haemolytic uraemic syndrome (HUS) is defined by the simultaneous occurrence of nonimmune haemolytic anaemia, thrombocytopenia and acute renal failure. This leads to the... (Review)
Review
Haemolytic uraemic syndrome (HUS) is defined by the simultaneous occurrence of nonimmune haemolytic anaemia, thrombocytopenia and acute renal failure. This leads to the pathological lesion termed thrombotic microangiopathy, which mainly affects the kidney, as well as other organs. HUS is associated with endothelial cell injury and platelet activation, although the underlying cause may differ. Most cases of HUS are associated with gastrointestinal infection with Shiga toxin-producing enterohaemorrhagic Escherichia coli (EHEC) strains. Atypical HUS (aHUS) is associated with complement dysregulation due to mutations or autoantibodies. In this review, we will describe the causes of HUS. In addition, we will review the clinical, pathological, haematological and biochemical features, epidemiology and pathogenetic mechanisms as well as the biochemical, microbiological, immunological and genetic investigations leading to diagnosis. Understanding the underlying mechanisms of the different subtypes of HUS enables tailoring of appropriate treatment and management. To date, there is no specific treatment for EHEC-associated HUS but patients benefit from supportive care, whereas patients with aHUS are effectively treated with anti-C5 antibody to prevent recurrences, both before and after renal transplantation.
Topics: Diagnosis, Differential; Hemolytic-Uremic Syndrome; Humans; Prognosis
PubMed: 27723152
DOI: 10.1111/joim.12546 -
Medicina Clinica Nov 2015The hemolytic uremic syndrome (HUS) is a clinical entity characterized by thrombocytopenia, non-immune hemolytic anemia and renal impairment. Kidney pathology shows... (Review)
Review
The hemolytic uremic syndrome (HUS) is a clinical entity characterized by thrombocytopenia, non-immune hemolytic anemia and renal impairment. Kidney pathology shows thrombotic microangiopathy (TMA) with endothelial cell injury leading to thrombotic occlusion of arterioles and capillaries. Traditionally, HUS was classified in 2 forms: Typical HUS, most frequently occurring in children and caused by Shiga-toxin-producing bacteria, and atypical HUS (aHUS). aHUS is associated with mutations in complement genes in 50-60% of patients and has worse prognosis, with the majority of patients developing end stage renal disease. After kidney transplantation HUS may develop as a recurrence of aHUS or as de novo disease. Over the last years, many studies have demonstrated that complement dysregulation underlies the endothelial damage that triggers the development of TMA in most of these patients. Advances in our understanding of the pathogenic mechanisms of aHUS, together with the availability of novel therapeutic options, will enable better strategies for the early diagnosis and etiological treatment, which are changing the natural history of aHUS. This review summarizes the aHUS clinical entity and describes the role of complement dysregulation in the pathogenesis of aHUS. Finally, we review the differential diagnosis and the therapeutic options available to patients with aHUS.
Topics: Atypical Hemolytic Uremic Syndrome; Combined Modality Therapy; Humans; Prognosis
PubMed: 25433773
DOI: 10.1016/j.medcli.2014.08.006 -
Pediatric Nephrology (Berlin, Germany) Nov 2008Over the past decade, atypical hemolytic uremic syndrome (aHUS) has been demonstrated to be a disorder of the regulation of the complement alternative pathway. Among... (Review)
Review
Over the past decade, atypical hemolytic uremic syndrome (aHUS) has been demonstrated to be a disorder of the regulation of the complement alternative pathway. Among approximately 200 children with the disease, reported in the literature, 50% had mutations of the complement regulatory proteins factor H, membrane cofactor protein (MCP) or factor I. Mutations in factor B and C3 have also been reported recently. In addition, 10% of children have factor H dysfunction due to anti-factor H antibodies. Early age at onset appears as characteristic of factor H and factor I mutated patients, while MCP-associated HUS is not observed before age 1 year. Low C3 level may occur in patients with factor H and factor I mutation, while C3 level is generally normal in MCP-mutated patients. Normal plasma factor H and factor I levels do not preclude the presence of a mutation in these genes. The worst prognosis is for factor H-mutated patients, as 60% die or reach end-stage renal disease (ESRD) within the first year after onset of the disease. Patients with mutations in MCP have a relapsing course, but no patient has ever reached ESRD in the first year of the disease. Half of the patients with factor I mutations have a rapid evolution to ESRD, but half recover. Early intensive plasmatherapy appears to have a beneficial effect, except in MCP-mutated patients. There is a high risk of graft loss for HUS recurrence or thrombosis in all groups except the MCP-mutated group. Recent success of liver-kidney transplantation combined with plasmatherapy opens this option for patients with mutations of factors synthesized in the liver. New therapies such as factor H concentrate or complement inhibitors offer hope for the future.
Topics: Child; Complement System Proteins; Education, Medical, Continuing; Hemolytic-Uremic Syndrome; Humans
PubMed: 18594873
DOI: 10.1007/s00467-008-0872-4