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Atypical Hemolytic Uremic Syndrome in Children and Adults With the Hot Spot C3 Gene Variant p.Arg161Trp

Lieke Ter Steeg1, Romy N Bouwmeester1, Mendy Ter Avest2

  • 1Department of Pediatric Nephrology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.

Kidney International Reports
|June 19, 2026
PubMed

Insights

The C3 p.Arg161Trp variant causes atypical hemolytic uremic syndrome (CaHUS) with varied symptoms in children and adults. This condition is linked to a high risk of relapse, emphasizing the need for ongoing monitoring.

Area of Science:

  • Nephrology
  • Genetics
  • Hematology

Background:

  • A gain-of-function variant, C3 p.Arg161Trp, is identified in 25% of Dutch patients with complement-mediated atypical hemolytic uremic syndrome (CaHUS).
  • Understanding the clinical spectrum of this specific variant is crucial for patient management.

Purpose of the Study:

  • To describe the clinical phenotype and outcomes of CaHUS associated with the C3 p.Arg161Trp variant.
  • To compare presentation and disease course between pediatric and adult patients.

Main Methods:

  • Retrospective, observational study of Dutch CaHUS patients with the C3 p.Arg161Trp variant identified before October 2023.
  • Analysis of clinical data including demographics, onset presentation, treatment (eculizumab), kidney function, and relapse rates.

Main Results:

  • 37 patients (11 children, 26 adults) were included. Children showed more severe hemolysis but less acute kidney injury compared to adults.
  • Adults had a higher incidence of end-stage kidney disease within a year. Eculizumab improved kidney recovery in adults.
  • High relapse rates were observed in both children (82%) and adults (86%), with a median time to relapse of 1.9 years.

Conclusions:

  • The C3 p.Arg161Trp variant leads to heterogeneous CaHUS phenotypes with distinct differences between children and adults.
  • Children experience more pronounced hemolysis but milder acute kidney injury.
  • The C3 p.Arg161Trp variant is associated with a significant risk of disease relapse.
Abstract

Keywords:
C3 p.Arg161Trpatypical hemolytic uremic syndromeclinical phenotypecomplementeculizumabthrombotic microangiopathy

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