Distinguishing characteristics of pediatric patients with primary hyperoxaluria type 1 in PEDSnet.

Characteristics Children Primary hyperoxaluria

Journal

Journal of pediatric urology
ISSN: 1873-4898
Titre abrégé: J Pediatr Urol
Pays: England
ID NLM: 101233150

Informations de publication

Date de publication:
06 Oct 2023
Historique:
received: 28 06 2023
revised: 04 09 2023
accepted: 01 10 2023
medline: 18 10 2023
pubmed: 18 10 2023
entrez: 17 10 2023
Statut: aheadofprint

Résumé

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inborn error of metabolism that causes oxalate deposition, leading to recurrent calcium oxalate kidney stones, chronic kidney disease and systemic oxalosis, which produces a broad range of serious life-threatening complications. Patients with PH1 have delayed diagnosis due to the rarity of the disease and the overlap with early-onset kidney stone disease not due to primary hyperoxaluria. The objective of this study was to determine the clinical features of individuals <21 years of age with PH1 that precede its diagnosis. We hypothesized that a parsimonious set of features could be identified that differentiate patients with PH1 from patients with non-primary hyperoxaluria-associated causes of early-onset kidney stone disease. We determined the association between clinical characteristics and PH1 diagnosis in a case-control study conducted between 2009 and 2021 in PEDSnet, a clinical research network of eight US pediatric health systems. Each patient with genetically confirmed PH1 was matched by sex and PEDSnet institution to up to 4 control patients with kidney stones without PH of any type. We obtained patient characteristics and diagnostic test results occurring before to less than 6 months after study entrance from a centralized database query and from manual chart review. Differences were examined using standardized differences and multivariable regression. The study sample included 37 patients with PH1 and 147 controls. Patients with PH1 were younger at diagnosis (median age of 3 vs 13.5 years); 75 % of children with PH1 were less than 8 years-old. Patients with PH1 were more likely to have combinations of nephrocalcinosis on ultrasound or CT (43 % vs 3 %), lower eGFR at diagnosis (median = 52 mL/min/1.73 m Children with PH1 are characterized by presentation before adolescence, nephrocalcinosis, decreased eGFR at diagnosis, and calcium oxalate monohydrate stone composition. If externally validated, these characteristics could facilitate earlier diagnosis and treatment of children with PH1.

Sections du résumé

BACKGROUND BACKGROUND
Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inborn error of metabolism that causes oxalate deposition, leading to recurrent calcium oxalate kidney stones, chronic kidney disease and systemic oxalosis, which produces a broad range of serious life-threatening complications. Patients with PH1 have delayed diagnosis due to the rarity of the disease and the overlap with early-onset kidney stone disease not due to primary hyperoxaluria.
OBJECTIVE OBJECTIVE
The objective of this study was to determine the clinical features of individuals <21 years of age with PH1 that precede its diagnosis. We hypothesized that a parsimonious set of features could be identified that differentiate patients with PH1 from patients with non-primary hyperoxaluria-associated causes of early-onset kidney stone disease.
STUDY DESIGN METHODS
We determined the association between clinical characteristics and PH1 diagnosis in a case-control study conducted between 2009 and 2021 in PEDSnet, a clinical research network of eight US pediatric health systems. Each patient with genetically confirmed PH1 was matched by sex and PEDSnet institution to up to 4 control patients with kidney stones without PH of any type. We obtained patient characteristics and diagnostic test results occurring before to less than 6 months after study entrance from a centralized database query and from manual chart review. Differences were examined using standardized differences and multivariable regression.
RESULTS RESULTS
The study sample included 37 patients with PH1 and 147 controls. Patients with PH1 were younger at diagnosis (median age of 3 vs 13.5 years); 75 % of children with PH1 were less than 8 years-old. Patients with PH1 were more likely to have combinations of nephrocalcinosis on ultrasound or CT (43 % vs 3 %), lower eGFR at diagnosis (median = 52 mL/min/1.73 m
CONCLUSIONS CONCLUSIONS
Children with PH1 are characterized by presentation before adolescence, nephrocalcinosis, decreased eGFR at diagnosis, and calcium oxalate monohydrate stone composition. If externally validated, these characteristics could facilitate earlier diagnosis and treatment of children with PH1.

Identifiants

DOI: 10.1016/j.jpurol.2023.10.001 PMID: 37848358
pubmed: 37848358
pii: S1477-5131(23)00426-6
doi: 10.1016/j.jpurol.2023.10.001
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Disclosures Gregory Tasian is on the Scientific Advisory Board of, is a consultant for, and receives research funding from NovoNordisk and Alnylam Pharmaceuticals. Akanksha Mittal and Nathan Cheng are employed by Alnylam Pharmaceuticals. Alnylam Pharmaceutics funded this study.

Auteurs

Gregory E Tasian (GE)

Department of Surgery, Division of Urology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: tasiang@chop.edu.

Kimberley Dickinson (K)

Applied Clinical Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Grace Park (G)

Applied Clinical Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Nicole Marchesani (N)

Applied Clinical Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Akanksha Mittal (A)

Alnylam Pharmaceuticals, Cambridge, MA, USA.

Nathan Cheng (N)

Alnylam Pharmaceuticals, Cambridge, MA, USA.

Christina B Ching (CB)

Department of Pediatric Urology, Nationwide Children's Hospital, Columbus, OH, USA.

David I Chu (DI)

Department of Surgery, Division of Urology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.

Ryan Walton (R)

Department of Surgery, Division of Urology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.

Karyn Yonekawa (K)

Department of Pediatrics, Division of Nephrology, Seattle Children's Hospital, Seattle, WA, USA.

Caroline Gluck (C)

Department of Pediatrics, Division of Nephrology, Nemours Children's Health, Wilmington, DE, USA.

Samina Muneeruddin (S)

Department of Pediatrics, Division of Nephrology, Nemours Children's Health, Wilmington, DE, USA.

Kathleen M Kan (KM)

Department of Surgery, Division of Urology, Stanford University, Palo Alto, CA, USA.

William DeFoor (W)

Department of Surgery, Division of Urology, Cincinnati Children's Hospital and Medical Center, Cincinnati, OH, USA.

Kyle Rove (K)

Department of Pediatric Urology, Division of Urology, Children's Hospital Colorado, Aurora, CO, USA.

Christopher B Forrest (CB)

Applied Clinical Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Classifications MeSH