Major National Award Funds Comparative Effectiveness Research for Children with Rare Kidney Disease

Researchers at Children’s Hospital of Philadelphia announced that the Patient-Centered Outcomes Research Institute (PCORI) approved a five-year funding award to support Comparative Effectiveness of Immunosuppressive Treatments for Children with Nephrotic Syndrome (CARE-NS), a major new research initiative in pediatric kidney care. The researchers will study the benefits and risks of the three most used medications for children with nephrotic syndrome who cannot remain on steroid treatment.

Nephrotic syndrome affects fewer than 1,500 children in the United States each year. It causes large amounts of protein to spill into the urine, low protein levels in the blood, and swelling throughout the body. While many newly diagnosed patients respond to high-dose corticosteroids, the toxic effects of long-term steroid use mean that other treatment options are often needed.

The study will run from March 2027 through February 2032. It aims to give families and clinicians clearer evidence to guide treatment decisions for this rare but serious condition. The study will enroll 700 children and young adults younger than 24 with nephrotic syndrome who are starting one of three steroid-sparing immunosuppressive medicines known as mycophenolate, rituximab, or tacrolimus. It will run across 29 health care institutions in PEDSnet and seven other PCORnet clinical research networks. The research will also encompass a separate long-term cohort study that will use electronic health record data from 9,000 children, spanning 2009 to 2029, to examine outcomes years after these treatments were received.

Although these drugs can help reduce reliance on steroids, they may carry significant side effects, and researchers do not yet know which option is most effective for patients or how their side effects compare over time. None of the medications are FDA-approved specifically for use in children with nephrotic syndrome.

Parent partners, clinicians, and researchers in the Glomerular Learning Network (GLEAN) prioritized the evidence gaps around steroid-sparing immunosuppression in nephrotic syndrome and developed this study to improve the health and well-being of children with this rare kidney disease. CARE-NS will measure outcomes that matter most to patients and families, including time in steroid-free remission, risk of serious infection, symptoms, daily functioning, and overall well-being. CARE-NS builds on prior nephrology research studies conducted by GLEAN and PEDSnet, the only PCORnet network dedicated to pediatric research.

“By comparing treatment effectiveness and both short- and long-term safety concerns, CARE-NS is expected to be the largest and most comprehensive study of steroid-sparing treatment for childhood nephrotic syndrome conducted to date,” said Michelle Denburg, MD, MSCE, the lead investigator for CARE-NS, attending physician in CHOP’s Division of Nephrology, director of GLEAN and co-director of the Penn-CHOP Kidney Innovation Center. CARE-NS will be co-led by Christopher Forrest, MD, PhD, a health science researcher at CHOP and director of PEDSnet.

Findings from CARE-NS will be shared through webinars, infographics, videos, and in-person meetings, and will support a new clinical practice guideline and shared decision-making tools designed to help families and clinicians choose the best treatment path for childhood nephrotic syndrome.