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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2012  |  Volume : 23  |  Issue : 5  |  Page : 1074-1076
Complement evaluation in atypical hemolytic uremic syndrome: Current concepts

1 Pediatric Nephrology, Kidney and Urology Institute, Medanta, The Medicity Hospital, Gurgaon, Haryana 122001, India
2 Division of Nephrology and Hypertension, Hofstra North Shore-LIJ School of Medicine, Great Neck, NY, USA

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Date of Web Publication13-Sep-2012

How to cite this article:
Sethi SK, Jhaveri KD. Complement evaluation in atypical hemolytic uremic syndrome: Current concepts. Saudi J Kidney Dis Transpl 2012;23:1074-6

How to cite this URL:
Sethi SK, Jhaveri KD. Complement evaluation in atypical hemolytic uremic syndrome: Current concepts. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2021 Dec 7];23:1074-6. Available from: https://www.sjkdt.org/text.asp?2012/23/5/1074/100958
To the Editor,

Hemolytic uremic syndrome (HUS) has been conventionally called D+ (preceded by a diar­rhea/dysentery prodrome) or D- (in the absence of a prodrome). The D+ or D- classification of HUS may be misleading because post-diarrheal onset does not exclude the possibility of genetic atypical HUS. On the other hand, absence of a diarrheal prodrome also does not rule out  Escherichia More Details coli 0157:H7 colonization and resultant HUS. [1]

Triggering events are known precipitants of complement-associated HUS. In the French and Italian pediatric cohorts, the onset of comple­ment-associated HUS followed an upper respi­ratory tract infection, fever or diarrhea in 63% and 85% of patients from all sub-groups. Inte­restingly, diarrhea preceded HUS in 13 patients (28%) from all sub-groups, including 0157:H7 E. coli-associated bloody diarrhea in one child with a Membrane Co-factor Protein (MCP) or CD 46 mutation. [2],[3]

We recently reported a seven-month-old child with Factor H mutation HUS preceded by a prodrome of dysentery. [4] A recent report on auto-antibodies in HUS showed a prodrome preceding the HUS episode in 32 of 45 pa­tients. Gastrointestinal symptoms were seen in 84% (diarrhea in 53%), Mallory-Weiss syn­drome in two cases, infections in four cases (one varicella, one upper respiratory tract in­fection, one Shiga-like toxin producing E. coli, one Norovirus) and urticaria and face edema in two patients. [5]

Newer studies have also suggested the con­sumption of complement in Shiga-toxin-associated HUS. [6] Also, it is now known that Shiga toxin can activate complement and that it binds to Factor H and to the regions involved in sur­face recognition function. [7] In the recent epide­mic of E. Coli 0104:H4 in Germany and Europe, promising results were seen with the use of complement blockade inhibitor- Eculizumab. [8]

Our increased understanding of the molecular mechanisms responsible for both HUS and thrombotic thrombocytopenic purpura (TTP) has led to the need to re-examine the classi­fication of these diseases. A recent publication from the European Pediatric Research Group for HUS has suggested that a new classifi­cation based on etiology has to be adopted. [8],[9]

According to the recent guidelines, any pa­tient with HUS requires complement evalua­tion if there is no recent history of diarrhea, or even if the child had a history of diarrhea but the child is less than six months old, has an insidious onset, relapsing course, previous un­explained anemia, post-transplant recurrence and asynchronous family history. A work-up for atypical HUS includes C3 (plasma/serum), Factor H and factor I concentration (plasma/ serum), Factor H autoantibody, MCP (CD46), gene mutation analysis in Factor H, factor I, MCP, factor B and C3, ADAMTS13 (vWFcp) deficiency with or without inhibitor analysis (plasma) and defects in cobalamin metabolism, depending on the clinical case. [1],[10],[11]

Some important points always to be remem­bered in evaluation of atypical HUS are summarized in [Table 1]. Newer studies in the field of aHUS have added the analysis for mutations in thromobomodulin [12] and looking for auto-antibodies to Factor H, and genes encoding Factor H-related proteins (CFHR) [5] in the panel of investigations for the disease. It is important to find antibodies in HUS, as they may be trea­ted with immunosuppression. [5]
Table 1: Clinical questions and answers on the new literature available on the hemolytic uremic syndrome (HUS).

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   References Top

1.Ariceta G, Besbas N, Johnson S, et al. European Paediatric Study Group for HUS. Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol 2009;24:687-96.  Back to cited text no. 1
2.Sellier-Leclerc AL, Fremeaux-Bacchi V, Dragon-Durey MA, et al. Differential impact of com­plement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol 2007;18:2392-400.  Back to cited text no. 2
3.Loirat C, Noris M, Fremeaux-Bacchi V. Com­plement and the atypical hemolytic uremic syndrome in children. Pediatr Nephrol 2008;23: 1957-72.  Back to cited text no. 3
4.Sethi SK, Marie-Agnes DD, Thaker N, Hari P, Bagga A. Hemolytic uremic syndrome due to homozygous factor H deficiency. Clin Exp Nephrol 2009;13:526-30.  Back to cited text no. 4
5.Dragon-Durey MA, Sethi SK, Bagga A, et al. Clinical features of anti-FH autoantibodies- associated hemolytic uremic syndrome. JASN 2010;21:2180-7.  Back to cited text no. 5
6.Thurman JM, Marians R, Emlen W, et al. Alternative pathway of complement in children with diarrhea-associated hemolytic uremic syn­drome. Clin J Am Soc Nephrol 2009;4:1920-4.  Back to cited text no. 6
7.Orth D, Khan AB, Naim A, et al. Shiga toxin activates complement and binds factor H: Evidence for an active role of complement in hemolytic uremic syndrome. J Immunol 2009; 182:6394-400.  Back to cited text no. 7
8.Lapeyraque AL, Malina M, Fremeaux-Bacchi V, et al Eculizumab in severe Shiga-toxin-associated HUS. N Engl J Med 2011;364:2561-3.  Back to cited text no. 8
9.Besbas N, Karpman D, Landau D, et al. European Paediatric Research Group for HUS. A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders. Kidney Int. 2006;70:423-31.  Back to cited text no. 9
10.Taylor CM, Machin S, Wigmore SJ, Goodship TH; working party from the Renal Association, the British Committee for Standards in Haematology and the British Transplantation Society. Clinical practice guidelines for the management of atypical haemolytic uraemic syndrome in the United Kingdom. Br J Haematol. 2010;148:37-47.  Back to cited text no. 10
11.Loirat C, Noris M, Fremeaux-Bacchi V. Com­plement and the atypical hemolytic uremic syndrome in children. Pediatr Nephrol 2008; 23:1957-72.  Back to cited text no. 11
12.Delvaeye M, Noris M, De Vriese A, et al. Thrombomodulin mutations in atypical hemolytic-uremic syndrome. N Engl J Med 2009; 361:345-57.  Back to cited text no. 12

Correspondence Address:
Sidharth Kumar Sethi
Pediatric Nephrology, Kidney and Urology Institute, Medanta, The Medicity Hospital, Gurgaon, Haryana 122001
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DOI: 10.4103/1319-2442.100958

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