714 - Determining Clinical Characteristics of Pediatric Patients with Primary Hyperoxaluria Type I in PEDSnet

Poster Number: 714
Publication Number: 714.105

Kimberley Dickinson, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Gregory E. Tasian, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Julia Schuchard, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Grace Park, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Nicole Marchesani, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Akanksha Mittal, Alnylam Pharmaceuticals, Boston, MA, United States; Nathan H. Cheng, Alnylam Pharmaceuticals, Cambridge, MA, United States; Christina Ching, Nationwide Children's Hospital, Columbus, OH, United States; David Chu, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States; Karyn Yonekawa, Seattle Children's, seattle, WA, United States; Caroline Gluck, NemoursAlfred I. duPont Hospital for Children, Wilmington, DE, United States; Kathleen M. Kan, Lucile Packard Children's Hospital Stanford, Stanford, CA, United States; Kyle O. Rove, Children’s Hospital Colorado, Aurora, CO, United States; Christopher B. Forrest, Children's Hospital of Philadelphia, Philadelphia, PA, United States

Background: Primary hyperoxaluria type I (PH1) is a rare genetic condition characterized by overproduction of oxalate by the liver and impairment of the body’s ability to eliminate oxalate, producing a broad range of life-threatening complications. The rarity of PH1 presents complexities to studying the condition at a large scale. Lack of known strong predictors of PH1 may delay testing and treatment in a patient’s disease progression.

Objective: We sought to determine clinical features and health services utilization patterns of pediatric patients preceding diagnosis of PH1 in contrast with non-PH1 kidney stone formers in a retrospective case-control study in PEDSnet.

Design/Methods: We identified a cohort of patients with diagnosed PH1 before 21 years of age between 2009 and 2021 using PEDSnet, a learning health system composed of pediatric institutions across the United States that standardize their data to a common data model (CDM). We validated the presence and date of PH1 diagnosis through chart review at each PEDSnet institution. Each PH1 patient (case) was matched with up to four patients with kidney stones not due to PH1 (controls) in the PEDSnet CDM based on health system and sex. Additional chart review was performed to supplement CDM data with information in the medical record but not represented in a standardized fashion. After data collection and data quality assessment, we selected candidate predictor variables based on clinical importance and data availability. We required at least 10% capture of the variable in both cases and controls to be considered as a predictor to lessen effects influenced by missingness of data in one or both cohorts. We examined differences between cases and controls for each predictor using standardized mean differences (SMD).

Results: Our sample included 37 PH1 patients and 147 controls across 8 health systems. PH1 patients were more likely to have nephrocalcinosis (SMD 1.13) and less likely to have immobility (-0.51) than controls (Figure 1). They were on average younger (-1.36) and had lower estimated glomerular filtration rate (eGFR) (-1.65) at first diagnosis and had higher calcium oxalate monohydrate stone composition levels over the course of disease (2.5) (Figure 2).

Conclusion(s): A parsimonious set of readily ascertained clinical characteristics in a pediatric population, including very early onset kidney stone diagnosis, nephrocalcinosis, decreased eGFR, and lack of immobility, were strongly associated with PH1. These characteristics, when present, may help identify pediatric patients who have a high probability of PH1 and thus may benefit from genetic testing.