Abstract: FR-PO613
Natural History of Advanced Primary Hyperoxaluria Type 1: A Retrospective Study
Session Information
- Genetic Diseases: Tubulopathies
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Lieske, John C., Mayo Clinic, Rochester, Minnesota, United States
- Groothoff, Jaap, Emma Children's Hospital, Amsterdam, Netherlands
- Frishberg, Yaacov, Shaare Zedek Medical Center, Jerusalem, Israel
- Garrelfs, Sander Frederik, Emma Children's Hospital, Amsterdam, Netherlands
- Milliner, Dawn S., Mayo Clinic, Rochester, Minnesota, United States
- Magen, Daniella, Rambam Medical Center, Haifa, Israel
- Sellier-Leclerc, Anne-Laure All, CHU Lyon – Hôpital Femme-Mère-Enfant, Bron, France
- Shasha-Lavsky, Hadas, Galilee Medical Center, Nahariyya, Israel
- Bakkaloglu, Sevcan A., Gazi University Hospital, Ankara, Turkey
- Lemoine, Sandrine, CHU Lyon – Hôpital Edouard Herriot, Lyon, France
- Fuster, Daniel G., Bern University Hospital, Bern, Switzerland
- Devresse, Arnaud, Cliniques Universitaires Saint-Luc, Bruxelles, Belgium
- Cytter Kuint, Ruth, Shaare Zedek Medical Center, Jerusalem, Israel
- Kajbaf, Farshad, Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States
- Willey, Richard G., Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States
- Gansner, John M., Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States
Background
Primary hyperoxaluria 1 (PH1) is a genetic disease of oxalate overproduction that can cause progressive kidney damage and systemic oxalosis. We aimed to characterize the natural history of advanced PH1 in the context of standard of care.
Methods
In this retrospective, multinational chart review study, eligible patients had ≥4 healthcare visits related to PH1 spanning ≥6 months (except deceased patients) on or after January 1, 2000, and ≥2 eGFR values ≤45 mL/min/1.73m2 (or, if age <12 months, 2 serum creatinine values elevated for age [>ULN]). Diagnosis details, laboratory values, clinical events, and imaging data were collected. Patients were assigned to one or both of 2 cohorts, nondialysis (Cohort A) and hemodialysis (Cohort B). Censoring events included participation in a therapeutic clinical trial or initiation of lumasiran. Bone x-ray images were evaluated centrally for evidence of systemic oxalosis and graded using a novel bone oxalosis grading scale.
Results
Fifty-four patients met criteria for Cohort A and 53 for Cohort B; in total, 70 patients were analyzed with up to 21 years of data. Median age at cohort entry was 11.8 years and 12.2 years (Cohorts A and B, respectively); 28 and 13 patients, respectively, met cohort entry criteria prior to PH1 diagnosis. In Cohort A, eGFR slope was −2.8 mL/min/1.73m2/y (n=25). In Cohort B, patients underwent hemodialysis a median of 6 days/week (range 3–7; n=41) and 3.8 hours/session (range, 2–8; n=31). Overall, 42 patients underwent liver and/or kidney transplantation at least once (median age at first transplant, 15.3 years). Nineteen patients died at a median age of 3.9 years (range, 2.2–34.9); systemic oxalosis was evident in all. Among these, the primary cause of death was transplant-related or occurred within 6 months of transplant in 6 patients. Skeletal oxalosis grade improvement after liver-kidney transplantation generally took more than a year.
Conclusion
Advanced PH1 is associated with high morbidity and mortality; liver and/or kidney transplantation have frequently been pursued. Although liver transplantation corrects the metabolic defect, it also carries significant risk.
Funding
- Commercial Support – Alnylam Pharmaceuticals