Diagnosis and Treatment of the Hemolytic Uremic Syndrome Disease Spectrum in Developing Regions

 

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Abstract

There has been rapid progress in the understanding of the pathophysiology of the hemolytic uremic syndrome (HUS) disease spectrum; thus, complex diagnostic and therapeutic requirements have emerged in parallel. Current recommendations for diagnosis and therapy were rapidly adapted from the prior skilled scientific groundwork. However, such recommendations can be realized only when highly specialized laboratories and sufficient financial resources are available. Thus, many recommendations are not feasible for patients living and working in developing countries. More than one-third of the world's population has no access to essential drugs and more than half of this group lives in the poorest regions of Africa and Asia. From this perspective, distinct initial diagnostic and therapeutic recommendations, as well as international cooperations are needed to complete proper diagnostic work-ups in a stringent and cost-efficient manner and to enable patients to be adequately treated with available resources. However, while costs for complement-targeted drugs remain tremendously high, state-of-the-art treatment options remain unavailable for the vast majority of patients in developing areas.

• References

• 1 Van Weely S, Leufkens HG. Priority medicines for Europe and the world - a public health approach to innovation. In: Kaplan W, Laing R, , eds. Orphan Diseases. Geneva: World Health Organization; 2004: 95-100
  Google Scholar
• 2 Shayman JA. Thinking about rare kidney diseases. J Am Soc Nephrol 2006; 17 (1) 15-16
  PubMedGoogle Scholar
• 3 Mark Taylor C. Enterohaemorrhagic Escherichia coli and Shigella dysenteriae type 1-induced haemolytic uraemic syndrome. Pediatr Nephrol 2008; 23 (9) 1425-1431
  CrossrefPubMedGoogle Scholar
• 4 Fernández-Brando RJ, Bentancor LV, Mejías MP , et al. Update on the treatment of endemic hemolytic uremic syndrome. Pathogenesis and treatment of the most severe systemic complication of infections by Shiga toxin-producing Escherichia coli [in Spanish]. Medicina (B Aires) 2011; 71 (4) 383-389
  PubMedGoogle Scholar
• 5 López EL, Contrini MM, Glatstein E , et al. An epidemiologic surveillance of Shiga-like toxin-producing Escherichia coli infection in Argentinean children: risk factors and serum Shiga-like toxin 2 values. Pediatr Infect Dis J 2012; 31 (1) 20-24
  CrossrefPubMedGoogle Scholar
• 6 Srivastava RN, Moudgil A, Bagga A, Vasudev AS. Hemolytic uremic syndrome in children in northern India. Pediatr Nephrol 1991; 5 (3) 284-288
  CrossrefPubMedGoogle Scholar
• 7 Arora P, Kher V, Gupta A , et al. Pattern of acute renal failure at a referral hospital. Indian Pediatr 1994; 31 (9) 1047-1053
  PubMedGoogle Scholar
• 8 Lanewala A, Mubarak M, Akhter F, Aziz S, Bhatti S, Kazi JI. Pattern of pediatric renal disease observed in native renal biopsies in Pakistan. J Nephrol 2009; 22 (6) 739-746
  PubMedGoogle Scholar
• 9 Jamal A, Ramzan A. Renal and post-renal causes of acute renal failure in children. J Coll Physicians Surg Pak 2004; 14 (7) 411-415
  PubMedGoogle Scholar
• 10 Safouh H. The hemolytic uremic syndrome in Egyptian children. Paper presented at: 2nd International Conference on HUS-MPGN-PNH; June 13–June 15 2010 ; Innsbruck, Austria
  PubMedGoogle Scholar
• 11 Germani Y, Soro B, Vohito M, Morel O, Morvan J. Enterohaemorrhagic Escherichia coli in Central African Republic. Lancet 1997; 349 (9066) 1670
  PubMedGoogle Scholar
• 12 Shimelis D, Tadesse Y. Clinical profile of acute renal failure in children admitted to the department of pediatrics, Tikur Anbessa Hospital. Ethiop Med J 2004; 42 (1) 17-22
  PubMedGoogle Scholar
• 13 Bentancor AB, Ameal LA, Calviño MF, Martinez MC, Miccio L, Degregorio OJ. Risk factors for Shiga toxin-producing Escherichia coli infections in preadolescent schoolchildren in Buenos Aires, Argentina. J Infect Dev Ctries 2012; 6 (5) 378-386
  PubMedGoogle Scholar
• 14 Rivero MA, Passucci JA, Rodriguez EM, Signorini ML, Tarabla HD, Parma AE. Factors associated with sporadic verotoxigenic Escherichia coli infection in children with diarrhea from the Central Eastern Area of Argentina. Foodborne Pathog Dis 2011; 8 (8) 901-906
  CrossrefPubMedGoogle Scholar
• 15 Rivero MA, Passucci JA, Rodríguez EM, Parma AE. Seasonal variation of HUS occurrence and VTEC infection in children with acute diarrhoea from Argentina. Eur J Clin Microbiol Infect Dis 2012; 31 (6) 1131-1135
  CrossrefPubMedGoogle Scholar
• 16 de Souza RL, Abreu Carvalhaes JT, Sanae Nishimura L, de Andrade MC, Cabilio Guth BE. Hemolytic uremic syndrome in pediatric intensive care units in São Paulo, Brazil. Open Microbiol J 2011; 5: 76-82
  CrossrefPubMedGoogle Scholar
• 17 Contreras CA, Ochoa TJ, Ruiz J , et al. Phylogenetic relationships of Shiga toxin-producing Escherichia coli isolated from Peruvian children. J Med Microbiol 2011; 60 (Pt 5) 639-646
  CrossrefPubMedGoogle Scholar
• 18 Zambrano O P, Delucchi B A, Cavagnaro S F , et al. Hemolytic-uremic syndrome in Chile: clinical features, evolution and prognostic factors [in Spanish]. Rev Med Chil 2008; 136 (10) 1240-1246
  PubMedGoogle Scholar
• 19 Bhattacharya M, Dhingra D, Mantan M, Upare S, Sethi GR. Acute renal failure in children in a tertiary care center. Saudi J Kidney Dis Transpl 2013; 24 (2) 413-417
  CrossrefPubMedGoogle Scholar
• 20 Krishnamurthy S, Narayanan P, Prabha S , et al. Clinical profile of acute kidney injury in a pediatric intensive care unit from Southern India: a prospective observational study. Indian J Crit Care Med 2013; 17 (4) 207-213
  CrossrefPubMedGoogle Scholar
• 21 Hari P, Singla IK, Mantan M, Kanitkar M, Batra B, Bagga A. Chronic renal failure in children. Indian Pediatr 2003; 40 (11) 1035-1042
  PubMedGoogle Scholar
• 22 Xiong Y, Wang P, Lan R , et al. A novel Escherichia coli O157:H7 clone causing a major hemolytic uremic syndrome outbreak in China. PLoS ONE 2012; 7 (4) e36144
  CrossrefPubMedGoogle Scholar
• 23 Wang H, Jing HQ, Li HW , et al. Epidemiological study on an outbreak caused by E. coli O157:H7 in Jiangsu province [in Chinese]. Zhonghua Liu Xing Bing Xue Za Zhi 2004; 25 (11) 938-940
  PubMedGoogle Scholar
• 24 Al-Eisa A, Al-Hajeri M. Hemolytic uremic syndrome in Kuwaiti Arab children. Pediatr Nephrol 2001; 16 (12) 1093-1098
  CrossrefPubMedGoogle Scholar
• 25 Mahmoud AM, Al-Harbi MS, Al-Sowailem AM, Mattoo TK. Etiology, presentation and management of acute renal failure in Saudi children. Ann Saudi Med 1992; 12 (2) 196-200
  PubMedGoogle Scholar
• 26 Elzouki AY, Mirza K, Mahmood A, Al-Sowailem AM. Hemolytic uremic syndrome - clinical aspects and outcome of an outbreak: report of 28 cases. Ann Saudi Med 1995; 15 (2) 113-116
  PubMedGoogle Scholar
• 27 Al-Qarawi S, Fontaine RE, Al-Qahtani MS. An outbreak of hemolytic uremic syndrome associated with antibiotic treatment of hospital inpatients for dysentery. Emerg Infect Dis 1995; 1 (4) 138-140
  CrossrefPubMedGoogle Scholar
• 28 Al Harbi NN, Elawad ME, Al Homrany MA. Hemolytic-uremic syndrome in asir region. J Family Community Med 1996; 3 (1) 53-57
  PubMedGoogle Scholar
• 29 Hamed RM. The spectrum of chronic renal failure among Jordanian children. J Nephrol 2002; 15 (2) 130-135
  PubMedGoogle Scholar
• 30 Olowu WA, Adelusola KA. Pediatric acute renal failure in southwestern Nigeria. Kidney Int 2004; 66 (4) 1541-1548
  CrossrefPubMedGoogle Scholar
• 31 Olotu AI, Mithwani S, Newton CR. Haemolytic uraemic syndrome in children admitted to a rural district hospital in Kenya. Trop Doct 2008; 38 (3) 165-167
  CrossrefPubMedGoogle Scholar
• 32 Oneko M, Nyathi MN, Doehring E. Post-dysenteric hemolytic uremic syndrome in Bulawayo, Zimbabwe. Pediatr Nephrol 2001; 16 (12) 1142-1145
  CrossrefPubMedGoogle Scholar
• 33 Bhimma R, Rollins NC, Coovadia HM, Adhikari M. Post-dysenteric hemolytic uremic syndrome in children during an epidemic of Shigella dysentery in Kwazulu/Natal. Pediatr Nephrol 1997; 11 (5) 560-564
  CrossrefPubMedGoogle Scholar
• 34 Leban N, Aloui S, Touati D , et al. Atypical hemolytic uremic syndrome in the Tunisian population. Int Urol Nephrol 2011; 43 (2) 559-564
  CrossrefPubMedGoogle Scholar
• 35 Mehrazma M, Hooman N, Otukesh H. Prognostic value of renal pathological findings in children with atypical hemolytic uremic syndrome. Iran J Kidney Dis 2011; 5 (6) 380-385
  PubMedGoogle Scholar
• 36 Safouh H, Riedl M, Jeller V , et al. Causes of the atypical hemolytic uremic syndrome in Egyptian children. Poster presented at: 16th Congress of the International Pediatric Nephrology Association; August 30–September 3 2013: Shanghai, China
  PubMedGoogle Scholar
• 37 Farthing M, Lindberg G, Dite P , et al. World Gastroenterology Organisation practice guideline: Acute diarrhea. 2008 ; pp 1–29, Available at: http://www.worldgastroenterology.org/acute-diarrhea-in-adults.html . Accessed: May 1, 2014
  PubMedGoogle Scholar
• 38 Fischer Walker CL, Perin J, Aryee MJ, Boschi-Pinto C, Black RE. Diarrhea incidence in low- and middle-income countries in 1990 and 2010: a systematic review. BMC Public Health 2012; 12: 220
  CrossrefPubMedGoogle Scholar
• 39 Ake JA, Jelacic S, Ciol M , et al. Relative nephroprotection during Escherichia coliO157:H7 infections: association with intravenous volume expansion. Pediatrics 2005; 115 (6) e673-680
  CrossrefPubMedGoogle Scholar
• 40 Burton-MacLeod JA, Kane EM, Beard RS, Hadley LA, Glass RI, Ando T. Evaluation and comparison of two commercial enzyme-linked immunosorbent assay kits for detection of antigenically diverse human noroviruses in stool samples. J Clin Microbiol 2004; 42 (6) 2587-2595
  CrossrefPubMedGoogle Scholar
• 41 Rosales A, Hofer J, Zimmerhackl LB , et al; German-Austrian HUS Study Group. Need for long-term follow-up in enterohemorrhagic Escherichia coli-associated hemolytic uremic syndrome due to late-emerging sequelae. Clin Infect Dis 2012; 54 (10) 1413-1421
  CrossrefPubMedGoogle Scholar
• 42 Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 2005; 365 (9464) 1073-1086
  PubMedGoogle Scholar
• 43 Lapeyraque AL, Malina M, Fremeaux-Bacchi V , et al. Eculizumab in severe Shiga-toxin-associated HUS. N Engl J Med 2011; 364 (26) 2561-2563
  CrossrefPubMedGoogle Scholar
• 44 Orth-Höller D, Würzner R. Role of complement in enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome. Semin Thromb Hemost 2014; 40 (4) 503-507
  Article in Thieme ConnectPubMedGoogle Scholar
• 45 Awasthi S, Agarwal GG, Mishra V , et al. Four-country surveillance of intestinal intussusception and diarrhoea in children. J Paediatr Child Health 2009; 45 (3) 82-86
  CrossrefPubMedGoogle Scholar
• 46 Zhang X, McDaniel AD, Wolf LE, Keusch GT, Waldor MK, Acheson DW. Quinolone antibiotics induce Shiga toxin-encoding bacteriophages, toxin production, and death in mice. J Infect Dis 2000; 181 (2) 664-670
  CrossrefPubMedGoogle Scholar
• 47 Safdar N, Said A, Gangnon RE, Maki DG. Risk of hemolytic uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 enteritis: a meta-analysis. JAMA 2002; 288 (8) 996-1001
  CrossrefPubMedGoogle Scholar
• 48 Wong CS, Mooney JC, Brandt JR , et al. Risk factors for the hemolytic uremic syndrome in children infected with Escherichia coli O157:H7: a multivariable analysis. Clin Infect Dis 2012; 55 (1) 33-41
  CrossrefPubMedGoogle Scholar
• 49 Bell BP, Griffin PM, Lozano P, Christie DL, Kobayashi JM, Tarr PI. Predictors of hemolytic uremic syndrome in children during a large outbreak of Escherichia coli O157:H7 infections. Pediatrics 1997; 100 (1) E12
  CrossrefPubMedGoogle Scholar
• 50 Nelson JM, Griffin PM, Jones TF, Smith KE, Scallan E. Antimicrobial and antimotility agent use in persons with shiga toxin-producing Escherichia coli O157 infection in FoodNet Sites. Clin Infect Dis 2011; 52 (9) 1130-1132
  CrossrefPubMedGoogle Scholar
• 51 Osswald H, Gleiter C. Hypernatremia and kidney function [in German]. Zentralbl Chir 1993; 118 (5) 267-272
  PubMedGoogle Scholar
• 52 Farquhar WB, Morgan AL, Zambraski EJ, Kenney WL. Effects of acetaminophen and ibuprofen on renal function in the stressed kidney. J Appl Physiol (1985) 1999; 86 (2) 598-604
  PubMedGoogle Scholar
• 53 Gianviti A, Tozzi AE, De Petris L , et al. Risk factors for poor renal prognosis in children with hemolytic uremic syndrome. Pediatr Nephrol 2003; 18 (12) 1229-1235
  CrossrefPubMedGoogle Scholar
• 54 Roumenina LT, Loirat C, Dragon-Durey MA, Halbwachs-Mecarelli L, Sautes-Fridman C, Fremeaux-Bacchi V. Alternative complement pathway assessment in patients with atypical HUS. J Immunol Methods 2011; 365 (1-2) 8-26
  CrossrefPubMedGoogle Scholar
• 55 Safouh H. HUS in Developing Countries: Diagnostic and Therapeutic Difficulties. Paper presented at: 3rd International Conference on HUS-MPGN-PNH; May 22–24, 2011; Innsbruck, Austria
  PubMedGoogle Scholar
• 56 Michon B, Moghrabi A, Winikoff R , et al. Complications of apheresis in children. Transfusion 2007; 47 (10) 1837-1842
  CrossrefPubMedGoogle Scholar
• 57 Witt V, Stegmayr B, Ptak J , et al. World apheresis registry data from 2003 to 2007, the pediatric and adolescent side of the registry. Transfus Apheresis Sci 2008; 39 (3) 255-260
  CrossrefPubMedGoogle Scholar
• 58 Bamgboye EL. Barriers to a functional renal transplant program in developing countries. Ethn Dis 2009; 19 (1, Suppl 1) S1-S56 , 9
  PubMedGoogle Scholar
• 59 Rizvi SA, Naqvi SA, Hussain Z , et al. Renal transplantation in developing countries. Kidney Int Suppl 2003; (83) S96-S100
  PubMedGoogle Scholar
• 60 Akoh JA. Renal transplantation in developing countries. Saudi J Kidney Dis Transpl 2011; 22 (4) 637-650
  PubMedGoogle Scholar
• 61 Legendre CM, Licht C, Muus P , et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 2013; 368 (23) 2169-2181
  CrossrefPubMedGoogle Scholar
• 62 Zuber J, Le Quintrec M, Sberro-Soussan R, Loirat C, Frémeaux-Bacchi V, Legendre C. New insights into postrenal transplant hemolytic uremic syndrome. Nat Rev Nephrol 2011; 7 (1) 23-35
  CrossrefPubMedGoogle Scholar
• 63 Campistol JM, Arias M, Ariceta G , et al. An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document. Nefrologia 2013; 33 (1) 27-45
  PubMedGoogle Scholar
• 64 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. Nat Rev Nephrol 2012; 8 (11) 643-657
  CrossrefPubMedGoogle Scholar
• 65 Westra D, Wetzels JF, Volokhina EB, van den Heuvel LP, van de Kar NC. A new era in the diagnosis and treatment of atypical haemolytic uraemic syndrome. Neth J Med 2012; 70 (3) 121-129
  PubMedGoogle Scholar
• 66 United Nations, Department of Economic and Social Affairs, Population Division World Population Prospects: The 2010 Revision, Volume I (Comprehensive Tables) and II (Demographic Profiles) 2011 ; Available at: http://esa.un.org/unpd/wpp/Documentation/WPP%202010%20publications.htm . Accessed: May 1, 2014
  PubMed
• 67 Riedl M, Fakhouri F, Le Quintrec M , et al. The spectrum of complement-mediated thrombotic microangiopathies—pathogenetic insights identifying novel treatment approaches. Semin Thromb Hemost 2014; 40 (4) 444-464
  Article in Thieme ConnectPubMedGoogle Scholar
• 68 Hassenpflug WA, Budde U, Schneppenheim S, Schneppenheim R. Inherited thrombotic thrombocytopenic purpura in children. Semin Thromb Hemost 2014; 40 (4) 487-492
  Article in Thieme ConnectPubMedGoogle Scholar
• 69 Knöbl P. Inherited and acquired thrombotic thrombocytopenic purpura (TTP) in adults. Semin Thromb Hemost 2014; 40 (4) 493-502
  Article in Thieme ConnectPubMedGoogle Scholar
• 70 Hofer J, Giner T, Józsi M. Complement factor H-antibody-associated hemolytic uremic syndrome: pathogenesis, clinical presentation, and treatment. Semin Thromb Hemost 2014; 40 (4) 431-443
  Article in Thieme ConnectPubMedGoogle Scholar
• 71 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 (4) 687-696
  CrossrefPubMedGoogle Scholar
• 72 Würzner R, Riedl M, Rosales A, Orth-Höller D. Treatment of enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome (eHUS). Semin Thromb Hemost 2014; 40 (4) 508-516
  Article in Thieme ConnectPubMedGoogle Scholar