Intrafamilial Disease Heterogeneity in Primary Hyperoxaluria Type 1

• Published in: Kidney international reports Vol. 9; no. 10; pp. 3006 - 3015
• Main Authors: Deesker, Lisa J., Karacoban, Hazal A., Metry, Elisabeth L., Garrelfs, Sander F., Bacchetta, Justine, Boyer, Olivia, Collard, Laure, Devresse, Arnaud, Hayes, Wesley, Hulton, Sally-Anne, Martin-Higueras, Cristina, Moochhala, Shabbir H., Neuhaus, Thomas J., Oh, Jun, Prikhodina, Larisa, Sikora, Przemyslaw, Oosterveld, Michiel J.S., Groothoff, Jaap W., Mandrile, Giorgia, Beck, Bodo B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2024; Elsevier
• Subjects: Clinical Research; discordance; families; intrafamilial heterogeneity; kidney failure; PH1; primary hyperoxaluria; kidney failure; PH1; discordance; primary hyperoxaluria; intrafamilial heterogeneity; families
• ISSN: 2468-0249; 2468-0249
• DOI: 10.1016/j.ekir.2024.07.026

Primary hyperoxaluria type 1 (PH1) is known for its variable clinical course, even within families. However, the extent of this heterogeneity has not been well-studied. We aimed to analyze intrafamilial clinical heterogeneity and disease course among siblings in a large cohort of familial PH1 cases.
A retrospective registry study was performed using data from OxalEurope. All PH1 families with 2 or more affected siblings were included. A 6-point PH1 clinical outcome scoring system was developed to grade heterogeneity within a family. Intrafamilial clinical heterogeneity was defined as a score ≥2. Kaplan-Meier analyses were used to analyze differences in kidney survival between index cases and siblings.
We included 88 families, encompassing 193 patients with PH1. The median interquartile range (IQR) follow-up time was 7.8 (1.9–17) years. Intrafamilial clinical heterogeneity, as defined by our score, was found in 38 (43%) PH1 families. In 54% of the families, affected siblings had a better outcome than the index case. Clinically asymptomatic siblings at the time of their diagnosis had a significantly more favorable clinical outcome based on the authors’ scoring system than siblings with clinical signs and index cases (P < 0.001). Kaplan-Meier analyses revealed that index cases reached kidney failure at an earlier age and earlier in follow-up compared to siblings (P < 0.001).
Intrafamilial clinical heterogeneity was found in a substantial number of familial PH1 cases. Compared to index cases, siblings had significantly better clinical outcomes and kidney survival; thereby supporting the policy of family screening to diagnose affected siblings early to improve their prognosis.
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