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Atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS) is a rare systemic life-threatening disease with an unfavorable prognosis [1] [2] [3] [4] . The basis of aHUS, which affects both children and adults, is thrombotic microangiopathy (TMA) [4] [5] . With TMA, blood clots form in small blood vessels (vessels of the microvasculature) of various organs, which leads to the defeat of the latter, as a result of a sudden or gradual progression of which multiple organ failure develops [1] [3] [4] . The cause of aHUS in most cases is chronic (permanent) uncontrolled activation of the complement system , part of the body’s immune system, whose action is normally aimed at destroying infectious agents and removing immune complexes and dead cells [4] [5] [6] [7] [8 ] . The destructive effect of the complement system on the body’s own tissues is prevented by special proteins that normally regulate complement activation processes. However, with aHUS, this regulation is violated, mainly due to mutations in the genes of complement regulatory proteins , which leads to a violation of their functions [6] [8] . Failures in the action of controlling mechanisms lead to excessive activation of the complement system, which begins to attack the body’s own tissues [7] [8] . Rapid diagnosis and early initiation of adequate therapy improves the prognosis of the disease and reduces the risk of life-threatening complications of TMA, including terminal renal failure , stroke, or acute myocardial infarction [4] [9] [10] [11] .

Classification

Escherichia coli

aHUS is one of the forms of HUS ( hemolytic-uremic syndrome ). In the structure of HUS in children, aHUS accounts for 5-10% of cases, while in adults, most cases of HUS are aHUS [12] . In most cases, HUS in children is caused by infection with Escherichia coli bacteria that produce Shiga toxin. The infection-induced form of the disease in the modern classification is called STEC-HUS [12] . Previously, it was called D + HUS, i.e., HUS associated with diarrhea, in contrast (D-HUS), i.e. not associated with diarrhea or atypical (aHUS). Today, this terminology should be considered obsolete [13] , since in 30% of patients with ASH, the disease begins with diarrhea [12] .

Epidemiology

AHUS is classified as sporadic or familial [2] [14] ; its prevalence is independent of race, gender, and geographic location. [12] As with all rare diseases, data on the incidence of aHUS are limited. The European registry, which lists 167 pediatric patients, provides data on 3.3 cases per million children and lower prevalence in adults. [15] [16] A recent study of 214 patients with ASHU revealed similar incidence rates in children (41.6%) and adults (58.4%). [17] According to the Orphanet website (a portal dedicated to rare diseases and orphan drugs), the prevalence of aHUS ranges from 1 to 9 per million people. [18]

Pathogenesis

The main mechanism for the development of aHUS is chronic uncontrolled activation of the complement system, leading to damage to the vascular endothelium, and, as a result, damage to organs. [5] [6] Normally, the complement system attacks and destroys pathogens, such as bacteria, viruses and altered body cells, and removes cell debris. [7] [8] [19] There are 3 different ways to activate complement: classic , lectin and alternative . [8] In the first 2 pathways, complement activation occurs only as a result of binding to immune complexes or special microorganisms, respectively, and the alternative pathway is active continuously, which leads to the continuous formation of a membrane-attacking complex (MAC) causing cell lysis. [19] In order to avoid complement-mediated damage to healthy tissues and organs, it is important for the body to tightly regulate the complement system, which is done using complement regulation proteins [14] . Genetic changes in complement regulation proteins (such as CFH, CFB, CFI, MCP, and thrombomodulin ) due to mutations in the genes encoding the synthesis of these proteins upset the fragile balance of the alternative complement activation pathway during aHUS. [6] [20] [21] [22] The resulting constant uncontrolled activation of complement leads to continuous damage to endothelial cells (cells lining the inner surface of blood vessels), [4] [9] [20] [21] which is accompanied by a constant activation of platelets and white blood cells , inducing the processes of microthrombosis and inflammation in the vascular bed of vital organs and, consequently, their ischemia , leading to irreversible damage, multiple organ failure and even death. [23] [24]

Clinical picture

AHUS often begins with nonspecific symptoms: malaise and fatigue . [12] The vast majority of patients have kidney damage, including terminal renal failure (ESR) . [6] At the same time, along with an increase in blood creatinine , [25] [26] [27] a decrease in the estimated glomerular filtration rate (rSCF), [4] [26] other symptoms may also be noted: decreased urine output, edema , [5] severe or malignant arterial hypertension , [5] proteinuria . [25]

In addition to the kidneys , other body systems may also suffer: • A third of patients develop extrarenal thrombosis. [28] • Neurological disorders: about half of the patients have signs of brain damage : [29] confusion [30] , stroke , [29] [30] convulsions , [29] [30] com [29] [31] and encephalopathy [5] • Damage to the cardiovascular system: 43% of patients with ASHU have signs of damage to the heart and blood vessels, including cardiomyopathy with the development of heart failure; [25] [32] myocardial infarction, [11] [32] high blood pressure ( hypertension [1] [25] [32] and diffuse vasculopathy. [6] • Damage to the gastrointestinal tract: 37% of patients have symptoms from the gastrointestinal tract: [3] abdominal pain, [10] vomiting [33] or diarrhea. [13] In the most severe cases, signs of pancreatitis , [33] gastroenteritis , [5] Colitis , [10] liver necrosis [5] • Complications on the part of the eye: damage to the vessels of the eye. [34] • Skin lesions: [35] ulceration, petechial rash. [36] • Pulmonary complications [11] AHUS triggers can be different conditions accompanied by additional activation of the complement system and, therefore, a high risk of developing TMA. [5] [16] [36] [37] • Diarrhea / gastroenteritis • Upper respiratory tract infections • Pregnancy and childbirth • Malignant arterial hypertension • Kidney transplantation and bone marrow • Glomerulopathy • Systemic diseases, such as systemic lupus erythematosus (SLE) and scleroderma • Malignant neoplasms

Forecast

In the long term, the prognosis for aHUS is poor. [20] Up to 79% of patients with ASHU die or receive irreversible kidney damage (development of end-stage renal failure) within 3 years from the onset of the disease with the use of only supportive therapy [5] . Kidney transplantation for ESRD in patients with ASHU has previously been rare because of the high transplant rejection rate, reaching 90% for some types of mutations. The development of aHUS in a de novo graft is also possible. [14] In this regard, most patients with ASH who have reached ESRD receive dialysis treatment, which is associated with a worsening prognosis. [38] [39] Attempts have been made to combine liver and kidney transplantation with ASH, although this complex procedure is accompanied by a high mortality rate (1 out of 2 cases) [40] .

Diagnostics

AHUS manifests with clinical signs of TMA ( thrombocytopenia , microangiopathic hemolysis and symptoms of organ dysfunction, primarily acute renal damage) . [4] Since aHUS is not the only disease causing systemic TMA, it is extremely important to conduct differential diagnosis. Other major causes of TMA include thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome caused by Escherichia coli producing shiga toxin (STEC-HUS). [4] [41] [42] After confirming the TMA using diagnostic tests to detect thrombocytopenia, microangiopathic hemolysis and organ dysfunction, it is extremely important to conduct differential diagnostics to identify the underlying disease. An analysis of ADAMTS-13 activity can distinguish between TTP and aHUS, and a shiga toxin analysis can reveal STEC-HUS [4] : • ADAMTS-13 activity of 5% or less confirms the diagnosis of TTP. • A positive test for Shiga toxin in the blood or feces confirms the diagnosis of STEC-HUS. • ADAMTS-13 activity of more than 5% and the absence of Shiga-toxin in the stool analysis increases the likelihood of confirming the diagnosis of aHUS. In the absence of ADAMTS-13 analysis results, serum creatinine (SCr) and platelet counts in patients with TMA may predict ADAMTS-13 activity. [43] Serum creatinine levels above 150-200 μmol / L (more than 1.7-2.3 mg / dL) or platelet counts above 30 000 / mm3 virtually exclude the diagnosis of severe ADAMTS-13 deficiency and, therefore, TTP. [43] Although aHUS is a genetic disease, in 30–50% of patients a genetic mutation cannot be detected. [1] [4] [5] [44] Therefore, genetic analysis seems an unreliable method for diagnosing the disease. [1] [4] Not every known genetic mutation has a prognostic value. [4] The latter consideration, combined with the limited availability of genetic analysis due to its high cost and long waiting for results, allows us to conclude that genetic analysis is not necessary for the initial diagnosis and choice of treatment tactics for ASHU. [4] [45]

Treatment

Plasma exchange / plasma infusion (PO / PI)

Although PO / IP is widely used, there are no statistically reliable controlled trials of the safety and effectiveness of this method for aHUS [46] . In some patients, an improvement in hematological parameters was noted [4] , in others, dysregulation of complement and TMA persisted despite plasma replacement therapy [45] [47] . This may be explained by the fact that PO / IP is insufficient to remove mutant complement factors or to fill in the missing factors [9] [38] , which leads to an incomplete clinical response [4] [48] .

The American Apheresis Society has assigned recommendations for the use of plasma replacement therapy in the treatment of ASHU with a 2C / weak evidence category due to the “low” and “very low” quality of evidence in favor of its use [49] .

Permanent Dialysis

Patients with aHUS with the development of ESRD usually begin dialysis therapy, in which 5-year survival is 50% [50] . Since patients with aHUS on dialysis retain systemic and uncontrolled activation of complement [34] , complement activity is higher than in dialysis patients receiving this type of treatment due to other diseases [51] . In this regard, patients with aHUS undergoing dialysis have a risk of extrarenal TMA [34] [51] [52] [53] [54] [55] [56] .

Transplantation

Although kidney transplantation is performed in patients with aHUS, it does not affect the uncontrolled activation of complement, which leads to progressive systemic TMA [45] . Depending on the genetic mutation, up to 90% of patients with aHUS suffer a relapse after kidney transplantation [13] [45] . Uncontrolled activation of complement, which continues after a kidney transplant, leads to transplant rejection, which in most patients cannot be prevented with plasma replacement therapy [6] [57] . Combined liver and kidney transplantation is possible only in a very small number of patients due to the limited number of donor organs. In addition, inflammation and TMA develop in other organs, causing a high risk of an unfavorable outcome, which is considered excessive by many doctors and patients [5] [6] .

Eculizumab

Eculizumab is a humanized monoclonal antibody that binds the C5 complement component, which is responsible for the activation of the membrane-attacking complex (MAC) [9] [58] , and thus inhibits the uncontrolled activity of the terminal complement complex [58] . In Russia, as in Europe, today Eculizumab is the only complement activity inhibitor approved for the treatment of aHUS in children and adults.

Literature

Notes

  1. ↑ 1 2 3 4 5 Kavanagh D. , Goodship TH , Richards A. Atypical haemolytic uraemic syndrome. (English) // British Medical Bulletin. - 2006. - Vol. 77-78 . - P. 5-22 . - DOI : 10.1093 / bmb / ldl004 . - PMID 16968692 .
  2. ↑ 1 2 Caprioli J. , Noris M. , Brioschi S. , Pianetti G. , Castelletti F. , Bettinaglio P. , Mele C. , Bresin E. , Cassis L. , Gamba S. , Porrati F. , Bucchioni S. , Monteferrante G. , Fang CJ , Liszewski MK , Kavanagh D. , Atkinson JP , Remuzzi G. , International Registry of Recurrent and Familial HUS / TTP. Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. (Eng.) // Blood. - 2006 .-- 15 August ( vol. 108 , no. 4 ). - P. 1267-1279 . - DOI : 10.1182 / blood-2005-10-007252 . - PMID 16621965 .
  3. ↑ 1 2 3 Langman, C. (2012) Systemic Multi-Organ Complications In Atypical Hemolyticuremic Syndrome (aHUS): Retrospective Study In A Medical Practice Setting . From Haematologica 97 (s1), 195-196: Abstract 0490.
  4. ↑ 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Laurence J. Atypical hemolytic uremic syndrome (aHUS): making the diagnosis. (English) // Clinical Advances In Hematology & Oncology: H&O. - 2012 .-- October ( vol. 10 , no. 10 Suppl 17 ). - P. 1-12 . - PMID 23187605 .
  5. ↑ 1 2 3 4 5 6 7 8 9 10 11 12 Noris M. , Caprioli J. , Bresin E. , Mossali C. , Pianetti G. , Gamba S. , Daina E. , Fenili C. , Castelletti F. , Sorosina A. , Piras R. , Donadelli R. , Maranta R. , van der Meer I. , Conway EM , Zipfel PF , Goodship TH , Remuzzi G. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype . (English) // Clinical Journal Of The American Society Of Nephrology: CJASN. - 2010 .-- October ( vol. 5 , no. 10 ). - P. 1844-1859 . - DOI : 10.2215 / CJN.02210310 . - PMID 20595690 .
  6. ↑ 1 2 3 4 5 6 7 8 Loirat C. , Noris M. , Fremeaux-Bacchi V. Complement and the atypical hemolytic uremic syndrome in children. (English) // Pediatric Nephrology (Berlin, Germany). - 2008 .-- November ( vol. 23 , no. 11 ). - P. 1957-1972 . - DOI : 10.1007 / s00467-008-0872-4 . - PMID 18594873 .
  7. ↑ 1 2 3 Meri S. Loss of self-control in the complement system and innate autoreactivity. (Eng.) // Annals Of The New York Academy Of Sciences. - 2007 .-- August ( vol. 1109 ). - P. 93-105 . - DOI : 10.1196 / annals.1398.011 . - PMID 17785294 .
  8. ↑ 1 2 3 4 5 Walport MJ Complement. First of two parts. (Eng.) // The New England Journal Of Medicine. - 2001 .-- 5 April ( vol. 344 , no. 14 ). - P. 1058-1066 . - DOI : 10.1056 / NEJM200104053441406 . - PMID 11287977 .
  9. ↑ 1 2 3 4 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. (Eng.) // The New England Journal Of Medicine. - 2013 .-- 6 June ( vol. 368 , no. 23 ). - P. 2169-2181 . - DOI : 10.1056 / NEJMoa1208981 . - PMID 23738544 .
  10. ↑ 1 2 3 Ohanian M. , Cable C. , Halka K. Eculizumab safely reverses neurologic impairment and eliminates need for dialysis in severe atypical hemolytic uremic syndrome. (English) // Clinical Pharmacology: Advances And Applications. - 2011. - Vol. 3 . - P. 5-12 . - DOI : 10.2147 / CPAA.S17904 . - PMID 22287852 .
  11. ↑ 1 2 3 Sallée M. , Daniel L. , Piercecchi MD , Jaubert D. , Fremeaux-Bacchi V. , Berland Y. , Burtey S. Myocardial infarction is a complication of factor H-associated atypical HUS. (Eng.) // Nephrology, Dialysis, Transplantation: Official Publication Of The European Dialysis And Transplant Association - European Renal Association. - 2010 .-- June ( vol. 25 , no. 6 ). - P. 2028-2032 . - DOI : 10.1093 / ndt / gfq160 . - PMID 20305136 .
  12. ↑ 1 2 3 4 5 Loirat C. , Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. (Eng.) // Orphanet Journal Of Rare Diseases. - 2011 .-- 8 September ( vol. 6 ). - P. 60-60 . - DOI : 10.1186 / 1750-1172-6-60 . - PMID 21902819 .
  13. ↑ 1 2 3 Zuber J. , Le Quintrec M. , Sberro-Soussan R. , Loirat C. , Frémeaux-Bacchi V. , Legendre C. New insights into postrenal transplant hemolytic uremic syndrome. (Eng.) // Nature Reviews. Nephrology. - 2011 .-- January ( vol. 7 , no. 1 ). - P. 23-35 . - DOI : 10.1038 / nrneph.2010.155 . - PMID 21102542 .
  14. ↑ 1 2 3 Noris M. , Remuzzi G. Atypical hemolytic-uremic syndrome. (Eng.) // The New England Journal Of Medicine. - 2009 .-- October 22 ( vol. 361 , no. 17 ). - P. 1676-1687 . - DOI : 10.1056 / NEJMra0902814 . - PMID 19846853 .
  15. ↑ Zimmerhackl LB , Besbas N. , Jungraithmayr T. , van de Kar N. , Karch H. , Karpman D. , Landau D. , Loirat C. , Proesmans W. , Prüfer F. , Rizzoni G. , Taylor MC , European Study Group for Haemolytic Uraemic Syndromes and Related Disorders. Epidemiology, clinical presentation, and pathophysiology of atypical and recurrent hemolytic uremic syndrome. (English) // Seminars In Thrombosis And Hemostasis. - 2006 .-- March ( vol. 32 , no. 2 ). - P. 113-120 . - DOI : 10.1055 / s-2006-939767 . - PMID 16575686 .
  16. ↑ 1 2 Campistol JM , Arias M. , Ariceta G. , Blasco M. , Espinosa M. , Grinyó JM , Praga M. , Torra R. , Vilalta R. , Rodríguez de Córdoba S. An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document. (English) // Nefrologia: Publicacion Oficial De La Sociedad Espanola Nefrologia. - 2013 .-- 18 January ( vol. 33 , no. 1 ). - P. 27-45 . - DOI : 10.3265 / Nefrologia.pre2012.Nov.11781 . - PMID 23364625 .
  17. ↑ Fremeaux-Bacchi V. , Fakhouri F. , Garnier A. , Bienaimé F. , Dragon-Durey MA , Ngo S. , Moulin B. , Servais A. , Provot F. , Rostaing L. , Burtey S. , Niaudet P . , Deschênes G. , Lebranchu Y. , Zuber J. , Loirat C. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. (English) // Clinical Journal Of The American Society Of Nephrology: CJASN. - 2013 .-- April ( vol. 8 , no. 4 ). - P. 554-562 . - DOI : 10.2215 / CJN.04760512 . - PMID 23307876 .
  18. ↑ Orphanet from Search for a rare disease . accessed 2014 (03 June).
  19. ↑ 1 2 Meri, S., et al. (2008) Encyclopedia of Life Sciences (ELS), John Wiley & Sons, Ltd, Chichester.
  20. ↑ 1 2 3 Hirt-Minkowski P. , Dickenmann M. , Schifferli JA Atypical hemolytic uremic syndrome: update on the complement system and what is new. (English) // Nephron. Clinical Practice. - 2010 .-- Vol. 114 , no. 4 . - P. 219-235 . - DOI : 10.1159 / 000276545 . - PMID 20090363 .
  21. ↑ 1 2 Noris M. , Mescia F. , Remuzzi G. STEC-HUS, atypical HUS and TTP are all diseases of complement activation. (Eng.) // Nature Reviews. Nephrology. - 2012 .-- November ( vol. 8 , no. 11 ). - P. 622-633 . - DOI : 10.1038 / nrneph.2012.195 . - PMID 22986360 .
  22. ↑ Sellier-Leclerc AL , Fremeaux-Bacchi V. , Dragon-Durey MA , Macher MA , Niaudet P. , Guest G. , Boudailliez B. , Bouissou F. , Deschenes G. , Gie S. , Tsimaratos M. , Fischbach M. , Morin D. , Nivet H. , Alberti C. , Loirat C. , French Society of Pediatric Nephrology. Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. (англ.) // Journal Of The American Society Of Nephrology : JASN. — 2007. — August ( vol. 18 , no. 8 ). — P. 2392—2400 . — DOI : 10.1681/ASN.2006080811 . — PMID 17599974 .
  23. ↑ Caprioli J. , Castelletti F. , Bucchioni S. , Bettinaglio P. , Bresin E. , Pianetti G. , Gamba S. , Brioschi S. , Daina E. , Remuzzi G. , Noris M. , International Registry of Recurrent and Familial HUS/TTP. Complement factor H mutations and gene polymorphisms in haemolytic uraemic syndrome: the C-257T, the A2089G and the G2881T polymorphisms are strongly associated with the disease. (англ.) // Human Molecular Genetics. — 2003. — 15 December ( vol. 12 , no. 24 ). — P. 3385—3395 . — DOI : 10.1093/hmg/ddg363 . — PMID 14583443 .
  24. ↑ Sullivan M. , Rybicki LA , Winter A. , Hoffmann MM , Reiermann S. , Linke H. , Arbeiter K. , Patzer L. , Budde K. , Hoppe B. , Zeier M. , Lhotta K. , Bock A. , Wiech T. , Gaspert A. , Fehr T. , Woznowski M. , Berisha G. , Malinoc A. , Goek ON , Eng C. , Neumann HP Age-related penetrance of hereditary atypical hemolytic uremic syndrome. (англ.) // Annals Of Human Genetics. — 2011. — November ( vol. 75 , no. 6 ). — P. 639—647 . — DOI : 10.1111/j.1469-1809.2011.00671.x . — PMID 21906045 .
  25. ↑ 1 2 3 4 Neuhaus TJ , Calonder S. , Leumann EP Heterogeneity of atypical haemolytic uraemic syndromes. (англ.) // Archives Of Disease In Childhood. — 1997. — June ( vol. 76 , no. 6 ). — P. 518—521 . — DOI : 10.1136/adc.76.6.518 . — PMID 9245850 .
  26. ↑ 1 2 Ståhl AL , Vaziri-Sani F. , Heinen S. , Kristoffersson AC , Gydell KH , Raafat R. , Gutierrez A. , Beringer O. , Zipfel PF , Karpman D. Factor H dysfunction in patients with atypical hemolytic uremic syndrome contributes to complement deposition on platelets and their activation. (англ.) // Blood. — 2008. — 1 June ( vol. 111 , no. 11 ). — P. 5307—5315 . — DOI : 10.1182/blood-2007-08-106153 . — PMID 18268093 .
  27. ↑ Ariceta G. , Besbas N. , Johnson S. , Karpman D. , Landau D. , Licht C. , Loirat C. , Pecoraro C. , Taylor CM , Van de Kar N. , Vandewalle J. , Zimmerhackl LB , European Paediatric Study Group for HUS. Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. (англ.) // Pediatric Nephrology (Berlin, Germany). — 2009. — April ( vol. 24 , no. 4 ). — P. 687—696 . — DOI : 10.1007/s00467-008-0964-1 . — PMID 18800230 .
  28. ↑ Muus, P., et al. (2013), 18th Congress of the European Hematology Association , Stockholm, Sweden, June 13–16, 2013, Abstract B1774.
  29. ↑ 1 2 3 4 George JN How I treat patients with thrombotic thrombocytopenic purpura: 2010. (англ.) // Blood. — 2010. — 18 November ( vol. 116 , no. 20 ). — P. 4060—4069 . — DOI : 10.1182/blood-2010-07-271445 . — PMID 20686117 .
  30. ↑ 1 2 3 Vesely SK , George JN , Lämmle B. , Studt JD , Alberio L. , El-Harake MA , Raskob GE ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients. (англ.) // Blood. — 2003. — 1 July ( vol. 102 , no. 1 ). — P. 60—68 . — DOI : 10.1182/blood-2003-01-0193 . — PMID 12637323 .
  31. ↑ Noris M. , Bucchioni S. , Galbusera M. , Donadelli R. , Bresin E. , Castelletti F. , Caprioli J. , Brioschi S. , Scheiflinger F. , Remuzzi G. , International Registry of Recurrent and Familial HUS/TTP. Complement factor H mutation in familial thrombotic thrombocytopenic purpura with ADAMTS13 deficiency and renal involvement. (англ.) // Journal Of The American Society Of Nephrology : JASN. — 2005. — May ( vol. 16 , no. 5 ). — P. 1177—1183 . — DOI : 10.1681/ASN.2005010086 . — PMID 15800115 .
  32. ↑ 1 2 3 Noris M. , Remuzzi G. Cardiovascular complications in atypical haemolytic uraemic syndrome. (англ.) // Nature Reviews. Nephrology. — 2014. — March ( vol. 10 , no. 3 ). — P. 174—180 . — DOI : 10.1038/nrneph.2013.280 . — PMID 24419569 .
  33. ↑ 1 2 Dragon-Durey MA , Sethi SK , Bagga A. , Blanc C. , Blouin J. , Ranchin B. , André JL , Takagi N. , Cheong HI , Hari P. , Le Quintrec M. , Niaudet P. , Loirat C. , Fridman WH , Frémeaux-Bacchi V. Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome. (англ.) // Journal Of The American Society Of Nephrology : JASN. — 2010. — December ( vol. 21 , no. 12 ). — P. 2180—2187 . — DOI : 10.1681/ASN.2010030315 . — PMID 21051740 .
  34. ↑ 1 2 3 Larakeb A. , Leroy S. , Frémeaux-Bacchi V. , Montchilova M. , Pelosse B. , Dunand O. , Deschênes G. , Bensman A. , Ulinski T. Ocular involvement in hemolytic uremic syndrome due to factor H deficiency--are there therapeutic consequences? (англ.) // Pediatric Nephrology (Berlin, Germany). — 2007. — November ( vol. 22 , no. 11 ). — P. 1967—1970 . — DOI : 10.1007/s00467-007-0540-0 . — PMID 17619907 .
  35. ↑ Ardissino G. , Tel F. , Testa S. , Marzano AV , Lazzari R. , Salardi S. , Edefonti A. Skin involvement in atypical hemolytic uremic syndrome. (англ.) // American Journal Of Kidney Diseases : The Official Journal Of The National Kidney Foundation. — 2014. — April ( vol. 63 , no. 4 ). — P. 652—655 . — DOI : 10.1053/j.ajkd.2013.09.020 . — PMID 24290245 .
  36. ↑ 1 2 Fang CJ , Richards A. , Liszewski MK , Kavanagh D. , Atkinson JP Advances in understanding of pathogenesis of aHUS and HELLP. (англ.) // British Journal Of Haematology. — 2008. — November ( vol. 143 , no. 3 ). — P. 336—348 . — DOI : 10.1111/j.1365-2141.2008.07324.x . — PMID 18691170 .
  37. ↑ Liszewski MK , Atkinson JP Too much of a good thing at the site of tissue injury: the instructive example of the complement system predisposing to thrombotic microangiopathy. (англ.) // Hematology. American Society Of Hematology. Education Program. - 2011. - Vol. 2011 . — P. 9—14 . — DOI : 10.1182/asheducation-2011.1.9 . — PMID 22160006 .
  38. ↑ 1 2 Heinen S. , Pluthero FG , van Eimeren VF , Quaggin SE , Licht C. Monitoring and modeling treatment of atypical hemolytic uremic syndrome. (англ.) // Molecular Immunology. — 2013. — May ( vol. 54 , no. 1 ). — P. 84—88 . — DOI : 10.1016/j.molimm.2012.10.044 . — PMID 23220071 .
  39. ↑ Nester C. , Stewart Z. , Myers D. , Jetton J. , Nair R. , Reed A. , Thomas C. , Smith R. , Brophy P. Pre-emptive eculizumab and plasmapheresis for renal transplant in atypical hemolytic uremic syndrome. (англ.) // Clinical Journal Of The American Society Of Nephrology : CJASN. — 2011. — June ( vol. 6 , no. 6 ). — P. 1488—1494 . — DOI : 10.2215/CJN.10181110 . — PMID 21617085 .
  40. ↑ Bresin E. , Daina E. , Noris M. , Castelletti F. , Stefanov R. , Hill P. , Goodship TH , Remuzzi G. , International Registry of Recurrent and Familial HUS/TTP. Outcome of renal transplantation in patients with non-Shiga toxin-associated hemolytic uremic syndrome: prognostic significance of genetic background. (англ.) // Clinical Journal Of The American Society Of Nephrology : CJASN. — 2006. — January ( vol. 1 , no. 1 ). — P. 88—99 . — DOI : 10.2215/CJN.00050505 . — PMID 17699195 .
  41. ↑ Benz K. , Amann K. Thrombotic microangiopathy: new insights. (англ.) // Current Opinion In Nephrology And Hypertension. — 2010. — May ( vol. 19 , no. 3 ). — P. 242—247 . — DOI : 10.1097/MNH.0b013e3283378f25 . — PMID 20186056 .
  42. ↑ Zipfel PF , Heinen S. , Skerka C. Thrombotic microangiopathies: new insights and new challenges. (англ.) // Current Opinion In Nephrology And Hypertension. — 2010. — July ( vol. 19 , no. 4 ). — P. 372—378 . — DOI : 10.1097/MNH.0b013e32833aff4a . — PMID 20539230 .
  43. ↑ 1 2 Zuber J. , Fakhouri F. , Roumenina LT , Loirat C. , Frémeaux-Bacchi V. , French Study Group for aHUS/C3G. Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies. (англ.) // Nature Reviews. Nephrology. — 2012. — November ( vol. 8 , no. 11 ). — P. 643—657 . — DOI : 10.1038/nrneph.2012.214 . — PMID 23026949 .
  44. ↑ Kavanagh D. , Goodship TH Atypical hemolytic uremic syndrome, genetic basis, and clinical manifestations. (англ.) // Hematology. American Society Of Hematology. Education Program. - 2011. - Vol. 2011 . — P. 15—20 . — DOI : 10.1182/asheducation-2011.1.15 . — PMID 22160007 .
  45. ↑ 1 2 3 4 Kavanagh D. , Goodship TH Atypical hemolytic uremic syndrome. (англ.) // Current Opinion In Hematology. — 2010. — September ( vol. 17 , no. 5 ). — P. 432—438 . — DOI : 10.1097/MOH.0b013e32833cae86 . — PMID 20613506 .
  46. ↑ Loirat C. , Garnier A. , Sellier-Leclerc AL , Kwon T. Plasmatherapy in atypical hemolytic uremic syndrome. (англ.) // Seminars In Thrombosis And Hemostasis. — 2010. — September ( vol. 36 , no. 6 ). — P. 673—681 . — DOI : 10.1055/s-0030-1262890 . — PMID 20865645 .
  47. ↑ Riedl M , Hofer J , Rosales A , Giner T , Zimmerhackl LB , Würzner R , Jungraithmayr T. Initiale Plasmatherapie bei Patienten mit atypischem HUS: kein negativer Vorhersagewert für das Outcome nach einem Jahr (нем.) // Klinische Pädiatrie. — 2011. — März ( Bd. 223 , Nr. S 01 ). — ISSN 0300-8630 . — DOI : 10.1055/s-0031-1273832 .
  48. ↑ Sarode R. , Bandarenko N. , Brecher ME , Kiss JE , Marques MB , Szczepiorkowski ZM , Winters JL Thrombotic thrombocytopenic purpura: 2012 American Society for Apheresis (ASFA) consensus conference on classification, diagnosis, management, and future research. (англ.) // Journal Of Clinical Apheresis. — 2014. — June ( vol. 29 , no. 3 ). — P. 148—167 . — DOI : 10.1002/jca.21302 . — PMID 24136342 .
  49. ↑ Szczepiorkowski ZM , Winters JL , Bandarenko N. , Kim HC , Linenberger ML , Marques MB , Sarode R. , Schwartz J. , Weinstein R. , Shaz BH , Apheresis Applications Committee of the American Society for Apheresis. Guidelines on the use of therapeutic apheresis in clinical practice--evidence-based approach from the Apheresis Applications Committee of the American Society for Apheresis. (англ.) // Journal Of Clinical Apheresis. - 2010 .-- Vol. 25 , no. 3 . — P. 83—177 . — DOI : 10.1002/jca.20240 . — PMID 20568098 .
  50. ↑ ERA-EDTA Registry Annual Report 2011: «European Renal Association-European Dialysis and Transplant Association Registry», The Netherlands: , Department of Medical Informatics.
  51. ↑ 1 2 Békássy ZD , Kristoffersson AC , Cronqvist M. , Roumenina LT , Rybkine T. , Vergoz L. , Hue C. , Fremeaux-Bacchi V. , Karpman D. Eculizumab in an anephric patient with atypical haemolytic uraemic syndrome and advanced vascular lesions. (Eng.) // Nephrology, Dialysis, Transplantation: Official Publication Of The European Dialysis And Transplant Association - European Renal Association. - 2013 .-- November ( vol. 28 , no. 11 ). - P. 2899-2907 . - DOI : 10.1093 / ndt / gft340 . - PMID 24009284 .
  52. ↑ Davin JC , Gracchi V. , Bouts A. , Groothoff J. , Strain L. , Goodship T. Maintenance of kidney function following treatment with eculizumab and discontinuation of plasma exchange after a third kidney transplant for atypical hemolytic uremic syndrome associated with a CFH mutation. (English) // American Journal Of Kidney Diseases: The Official Journal Of The National Kidney Foundation. - 2010 .-- April ( vol. 55 , no. 4 ). - P. 708-711 . - DOI : 10.1053 / j.ajkd.2009.08.08.011 . - PMID 19854549 .
  53. ↑ Malina M. , Gulati A. , Bagga A. , Majid MA , Simkova E. , Schaefer F. Peripheral gangrene in children with atypical hemolytic uremic syndrome. (English) // Pediatrics. - 2013 .-- January ( vol. 131 , no. 1 ). - P. e331-335 . - DOI : 10.1542 / peds.2012-0903 . - PMID 23230076 .
  54. ↑ Remuzzi G. , Ruggenenti P. , Colledan M. , Gridelli B. , Bertani A. , Bettinaglio P. , Bucchioni S. , Sonzogni A. , Bonanomi E. , Sonzogni V. , Platt JL , Perico N. , Noris M Hemolytic uremic syndrome: a fatal outcome after kidney and liver transplantation performed to correct factor h gene mutation. (English) // American Journal Of Transplantation: Official Journal Of The American Society Of Transplantation And The American Society Of Transplant Surgeons. - 2005 .-- May ( vol. 5 , no. 5 ). - P. 1146-1150 . - DOI : 10.1111 / j.1600-6143.2005.00783.x . - PMID 15816899 .
  55. ↑ Vergouwen MD , Adriani KS , Roos YB , Groothoff JW , Majoie CB Proximal cerebral artery stenosis in a patient with hemolytic uremic syndrome. (English) // AJNR. American Journal of Neuroradiology. - 2008 .-- May ( vol. 29 , no. 5 ). - P. e34—34 . - DOI : 10.3174 / ajnr.A0965 . - PMID 18258702 .
  56. ↑ Loirat C. , Macher MA , Elmaleh-Berges M. , Kwon T. , Deschênes G. , Goodship TH , Majoie C. , Davin JC , Blanc R. , Savatovsky J. , Moret J. , Fremeaux-Bacchi V. Non -atheromatous arterial stenoses in atypical haemolytic uraemic syndrome associated with complement dysregulation. (Eng.) // Nephrology, Dialysis, Transplantation: Official Publication Of The European Dialysis And Transplant Association - European Renal Association. - 2010 .-- October ( vol. 25 , no. 10 ). - P. 3421—3425 . - DOI : 10.1093 / ndt / gfq319 . - PMID 20530807 .
  57. ↑ Le Quintrec M. , Zuber J. , Moulin B. , Kamar N. , Jablonski M. , Lionet A. , Chatelet V. , Mousson C. , Mourad G. , Bridoux F. , Cassuto E. , Loirat C. , Rondeau E. , Delahousse M. , Frémeaux-Bacchi V. Complement genes strongly predict recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome. (English) // American Journal Of Transplantation: Official Journal Of The American Society Of Transplantation And The American Society Of Transplant Surgeons. - 2013 .-- March ( vol. 13 , no. 3 ). - P. 663-675 . - DOI : 10.1111 / ajt.12077 . - PMID 23356914 .
  58. ↑ 1 2 Keating GM Eculizumab: a review of its use in atypical haemolytic uraemic syndrome. (English) // Drugs. - 2013 .-- December ( vol. 73 , no. 18 ). - P. 2053-2066 . - DOI : 10.1007 / s40265-013-0147-7 . - PMID 24249647 .
Source - https://ru.wikipedia.org/w/index.php?title=Atypical hemolytic - uremic syndrome &oldid = 100250859


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