Editorial Commentary

Pediatric Nephrology

, Volume 24, Issue 4, pp 687-696

First online:

Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome

  • Gema AricetaAffiliated withHospital de Cruces
  • , Nesrin BesbasAffiliated withPediatric Nephrology Unit, Department of Pediatrics, Faculty of Medicine, Hacettepe University
  • , Sally JohnsonAffiliated withDepartment of Nephrology, Birmingham Children’s Hospital
  • , Diana KarpmanAffiliated withDepartment of Paediatrics, Clinical Sciences Lund University
  • , Daniel LandauAffiliated withPediatric Nephrology, Soroka Medical Center
  • , Christoph LichtAffiliated withThe Hospital for Sick Children, University of Toronto
  • , Chantal LoiratAffiliated withAssistance Publique-Hopitaux de Paris, Universite Paris 7, Service de Nephrologie, Hopital Robert Debre
  • , Carmine PecoraroAffiliated withDepartment of Nephrology and Urology, Santobono Children’s Hospital
  • , C. Mark TaylorAffiliated withDepartment of Nephrology, Birmingham Children’s Hospital Email author 
    • , Nicole Van de KarAffiliated withUniversity Medical Center St Radboud
    • , Johan VandeWalleAffiliated withUZG Pediatrics, University Hospital
    • , Lothar B. ZimmerhacklAffiliated withUniversitäts-Klinik für Kinder-und Jugendheilkunde, Medizinische Universität Innsbruck
    • , The European Paediatric Study Group for HUS


This guideline for the investigation and initial treatment of atypical hemolytic uremic syndrome (HUS) is intended to offer an approach based on opinion, as evidence is lacking. It builds on the current ability to identify the etiology of specific diagnostic sub-groups of HUS. HUS in children is mostly due to infection, enterohemorrhagic Escherichia coli (EHEC), Shigella dysenteriae type 1 in some geographic regions, and invasive Streptococcus pneumoniae. These sub-groups are relatively straightforward to diagnose. Their management, which is outside the remit of this guideline, is related to control of infection where that is necessary and supportive measures for the anemia and acute renal failure. A thorough investigation of the remainder of childhood HUS cases, commonly referred to as “atypical” HUS, will reveal a risk factor for the syndrome in approximately 60% of cases. Disorders of complement regulation are, numerically, the most important. The outcome for children with atypical HUS is poor, and, because of the rarity of these disorders, clinical experience is scanty. Some cases of complement dysfunction appear to respond to plasma therapy. The therapeutic part of this guideline is the consensus of the contributing authors and is based on limited information from uncontrolled studies. The guideline proposes urgent and empirical plasmapheresis replacement with whole plasma fraction for the first month after diagnosis. This should only be undertaken in specialized pediatric nephrology centers where appropriate medical and nursing skills are available. The guideline includes defined terminology and audit points so that the early clinical effectiveness of the strategy can be evaluated.


Hemolytic uremic syndrome Atypical HUS Thrombotic thrombocytopenic purpura Enterohemorrhagic Escherichia coli Complement factor H Complement factor I Complement factor B Complement C3 Membrane co-factor protein MCP (CD46) A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) Plasmapheresis