TY - JOUR
T1 - Atypical Hemolytic Uremic Syndrome in Children and Adults With the Hot Spot C3 Gene Variant p.Arg161Trp
AU - ter Steeg, Lieke
AU - Bouwmeester, Romy N.
AU - ter Avest, Mendy
AU - Bemelman, Frederike J.
AU - Bouts, Antonia H.M.
AU - Bredewold, Obbo W.
AU - Dorresteijn, Eiske
AU - Eijgelsheim, Mark
AU - Engels, Flore A.P.T.
AU - Gracchi, Valentina
AU - Heine, Rob ter
AU - Keijzer-Veen, Mandy G.
AU - van de Logt, Anne Els
AU - van der Meijden, Wilbert A.G.
AU - van Rooij, Roos W.G.
AU - Severs, David
AU - Timmermans, Sjoerd A.M.E.G.
AU - van Zuilen, Arjan D.
AU - Michels, Marloes A.H.M.
AU - Wijnsma, Kioa L.
AU - van den Heuvel, Lambertus P.W.J.
AU - Wetzels, Jack F.M.
AU - Duineveld, Caroline
AU - van de Kar, Nicole C.A.J.
N1 - Publisher Copyright:
© 2026 The Author(s)
PY - 2026/8
Y1 - 2026/8
N2 - Introduction: The gain-of-function variant C3 p.Arg161Trp is found in a quarter of Dutch patients with complement-mediated atypical hemolytic uremic syndrome (CaHUS). In this study, we describe the clinical phenotype of C3 p.Arg161Trp–associated CaHUS. Methods: Dutch patients with CaHUS with the C3 p.Arg161Trp variant, identified before October 2023, were included in this retrospective, observational study. Results: A total of 37 patients (11 children and 26 adults) were included, with onset before and after availability of eculizumab. Presentation at onset differed between children and adults, specifically in platelet count (21 vs. 79 x 109/L, P = 0.036), lactate dehydrogenase (2644 vs. 1260 U/L, P = 0.026), estimated glomerular filtration rate (eGFR) (48 vs. 15 ml/min per 1.73 m2, P < 0.001), red-colored urine (90 vs. 24%, P = 0.001), and jaundice (50 vs. 10%, P = 0.022). None of the children developed end-stage kidney disease (ESKD) within a year after disease onset, in contrast to 11 of 26 adults. Ten children initially showed full recovery, of which 1 had received eculizumab. In adults, kidney function recovery occurred more often in those treated with eculizumab (88%, n = 7/8), compared with adults not treated with eculizumab (44%, n = 8/18). Relapse rate in the native kidneys of children and adults was high, 82% and 86%, respectively. The median (range) time between disease onset and relapse was 1.9 (0.3–17.6) years. Conclusion: The clinical phenotype of C3 p.Arg161Trp–associated CaHUS has significant heterogeneity, with differences in presentation and outcomes between children and adults. Children present with more profound hemolysis but milder acute kidney injury (AKI). Furthermore, C3 p.Arg161Trp is linked to a high risk of relapse.
AB - Introduction: The gain-of-function variant C3 p.Arg161Trp is found in a quarter of Dutch patients with complement-mediated atypical hemolytic uremic syndrome (CaHUS). In this study, we describe the clinical phenotype of C3 p.Arg161Trp–associated CaHUS. Methods: Dutch patients with CaHUS with the C3 p.Arg161Trp variant, identified before October 2023, were included in this retrospective, observational study. Results: A total of 37 patients (11 children and 26 adults) were included, with onset before and after availability of eculizumab. Presentation at onset differed between children and adults, specifically in platelet count (21 vs. 79 x 109/L, P = 0.036), lactate dehydrogenase (2644 vs. 1260 U/L, P = 0.026), estimated glomerular filtration rate (eGFR) (48 vs. 15 ml/min per 1.73 m2, P < 0.001), red-colored urine (90 vs. 24%, P = 0.001), and jaundice (50 vs. 10%, P = 0.022). None of the children developed end-stage kidney disease (ESKD) within a year after disease onset, in contrast to 11 of 26 adults. Ten children initially showed full recovery, of which 1 had received eculizumab. In adults, kidney function recovery occurred more often in those treated with eculizumab (88%, n = 7/8), compared with adults not treated with eculizumab (44%, n = 8/18). Relapse rate in the native kidneys of children and adults was high, 82% and 86%, respectively. The median (range) time between disease onset and relapse was 1.9 (0.3–17.6) years. Conclusion: The clinical phenotype of C3 p.Arg161Trp–associated CaHUS has significant heterogeneity, with differences in presentation and outcomes between children and adults. Children present with more profound hemolysis but milder acute kidney injury (AKI). Furthermore, C3 p.Arg161Trp is linked to a high risk of relapse.
KW - atypical hemolytic uremic syndrome
KW - C3 p.Arg161Trp
KW - clinical phenotype
KW - complement
KW - eculizumab
KW - thrombotic microangiopathy
UR - https://www.scopus.com/pages/publications/105041635917
U2 - 10.1016/j.ekir.2026.106599
DO - 10.1016/j.ekir.2026.106599
M3 - Article
AN - SCOPUS:105041635917
SN - 2468-0249
VL - 11
JO - Kidney International Reports
JF - Kidney International Reports
IS - 8
M1 - 106599
ER -