The CHOP/Nemours Children’s Health-led study leverages real-world data from six pediatric health systems in the PEDSnet database, overcoming the scale hurdle for a rare disease.
Chronic kidney disease (CKD) in children is rare, making it difficult to study and leaving important gaps in the quantity and quality of evidence informing the care of pediatric patients with the condition. Even the largest prospective studies have limited utility as they are limited by selection bias and relatively small sample sizes for different causes and courses of the disease.
In a new study led by Children’s Hospital of Philadelphia (CHOP) and Nemours Children’s Health, researchers overcame the scale hurdle by analyzing electronic health record data from PEDSnet, a national multicenter pediatric network, to identify a large cohort of children with CKD, evaluate the progression of CKD, and examine clinical risk factors for deterioration of renal function. The findings were published in the Clinical Journal of the American Society of Nephrology .
“The overall goal of this project was to demonstrate that real-world EHR data can be used to model decline in kidney function in children. Chronic kidney disease in children is rare and, as such, there are few high-quality studies to inform clinical decision making,” said Caroline Gluck, MD, a physician in the Division of Nephrology at Nemours Children’s Health, Delaware. "Unlike prospective cohort studies, this study represents an unbiased sample of the US source population and, to our knowledge, represents the largest cohort of children with CKD to date."
To better understand the factors that contribute to declining kidney function in patients with CKD, researchers focused on children from six pediatric health systems in the PEDSnet database who were seen between January 1, 2009 and February 28, 2022. Of more than 7.1 million children, researchers identified 11,240 (0.157%) with CKD. They divided the group into subcohorts according to the type of CKD: glomerular, non-glomerular and associated with malignancy. CKD progression was determined based on estimated glomerular filtration rate (eGFR), a calculated index of kidney function based on serum creatinine level that determines the stage of kidney disease; the need for long-term dialysis; and the need for a kidney transplant.
The researchers found that the following attributes in children with CKD were associated with a more rapid decline in kidney function: disease of glomerular origin or associated with malignancy; high levels of protein in the urine (proteinuria); hypertension; younger age; More advanced CKD; male sex; and greater medical complexity at the start of follow-up care .
For example, over a median follow-up time of five years, 40% of patients with glomerular CKD required long-term dialysis or transplantation or experienced a greater than 50% reduction in eGFR, while the same occurred with only 13% of patients with non-glomerular CKD.
Given the size of the population analyzed in the study, which also included children with cancer, who have a high burden of CKD but who have been excluded or underrepresented in previous studies, the findings may be more broadly applicable to the pediatric population. with CKD.
"Children with the risk factors identified in our study are of particular concern for CKD progression and may be the subject of comparative effectiveness studies to preserve kidney function," said lead author Michelle Denburg, MD, MSCE, a nephrologist. from Children’s Hospital of Philadelphia and co. -director of the CHOP Pediatric Center of Excellence in Nephrology and the Penn-CHOP Kidney Innovation Center. “The findings and methods of this study are critical for future research in children with CKD, including the PRESERVE study that I lead with Dr. Christopher Forrest, director of PEDSnet, which leverages EHR data from 16 pediatric health systems to analyze the blood. blood pressure management and preservation of renal function in pediatric CKD. “This study may also serve as a roadmap for the use of EHR data networks to adequately empower the study of rare diseases.”
This study was supported by grant U18FD006297 from the Institute for Advanced Clinical Trials for Children (iactc.org) under the FDA and by the Pediatric Nephrology Center of Excellence at the Children’s Hospital of Philadelphia and the National Institute of Diabetes and Digestive and Kidney Diseases. the Health Institutes with award number 5P50DK114786-05. The reported research was conducted using PEDSnet, a national pediatric learning health system, supported by PCORI award RI-CHOP-01-PS1. This study was partially funded through PCORI Award #RD-2020C2-20338.
