Sistema de Salut de Catalunya
Institut Català de la Salut
[Sas DJ] Division of Pediatric Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA. [Bakkaloglu SA] Department of Pediatric Nephrology, Gazi University, Ankara, Turkey. [Belostotsky V] Department of Pediatrics, McMaster Children’s Hospital, Hamilton, Canada. [Hayes W] Department of Pediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. [Ariceta G] Servei de Nefrologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Zhou J] Novo Nordisk A/S, Lexington, MA, USA
Vall d'Hebron Barcelona Hospital Campus
2025-05-06T09:49:26Z
2025-05-06T09:49:26Z
2025-06
Chronic kidney disease; Gene expression; Hyperoxaluria
Malaltia renal crònica; Expressió gènica; Hiperoxalúria
Enfermedad renal crónica; Expresión génica; Hiperoxaluria
Background: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder with dysregulated glyoxylate metabolism in the liver. Oxalate over-production leads to renal stones, progressive kidney damage and renal failure, with potentially life-threatening systemic oxalosis. Nedosiran is a synthetic RNA interference therapy, designed to reduce hepatic lactate dehydrogenase (LDH) to decrease oxalate burden in PH. Methods: Currently, in the PHYOX8 study (NCT05001269), pediatric participants (2-11 years) with PH1 (N = 15) and estimated glomerular filtration rate (eGFR) ≥ 30mL/min/1.73m2 received nedosiran once monthly for 6 months. Results: Urinary oxalate:creatinine (Uox:Ucr) levels reduced by 64% on average. Mean Uox:Ucr reduction was 52% at day 60 and ˃60% at day 180. At one or more study visits, 93.3% (N = 14) of participants reached Uox:Ucr < 1.5 × upper limit of normal (ULN), and 53.3% (N = 8) reached ≤ 1.0 × ULN. Median percent change in plasma oxalate (12.0 µmol/L at baseline) to day 180 was -39.23% (n = 10). Average number of kidney stones per participant remained stable, whilst a 10.1% average decrease in summed surface area was observed. Median percent change from baseline in eGFR was 2.5%, indicating preservation of renal function. Conclusions: Nedosiran was well tolerated, with only 3 participants experiencing at least one serious adverse event, none considered treatment-related. The incidence of injection site reactions was 6.7% (1/15 participants). In conclusion, nedosiran treatment led to a significant and sustained reduction of Uox levels in children with PH1. These findings support nedosiran treatment in pediatric patients to reduce Uox and shows promise for limiting PH1-related complications.
The study was supported by Dicerna Pharmaceuticals, Inc., a Novo Nordisk Company (Lexington, MA, USA).
Article
Published version
English
Avaluació de resultats (Assistència sanitària); Infants; Hidrats de carboni - Metabolisme - Trastorns - Tractament; Ronyons - Càncer - Tractament; DISEASES::Nutritional and Metabolic Diseases::Metabolic Diseases::Metabolism, Inborn Errors::Carbohydrate Metabolism, Inborn Errors::Hyperoxaluria, Primary; Other subheadings::Other subheadings::Other subheadings::/drug therapy; NAMED GROUPS::Persons::Age Groups::Child; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome; ENFERMEDADES::enfermedades nutricionales y metabólicas::enfermedades metabólicas::alteraciones congénitas del metabolismo::trastornos congénitos del metabolismo de los carbohidratos::hiperoxaluria primaria; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; DENOMINACIONES DE GRUPOS::personas::Grupos de Edad::niño; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento
Springer
Pediatric Nephrology;40
https://doi.org/10.1007/s00467-025-06675-8
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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