SGLT-2 inhibition in pediatric CKD: advances, challenges, and opportunities.

Abstract

This editorial comments on the report on a 2023 multistakeholder workshop addressing the development of sodium-glucose cotransporter-2 inhibitors for children with chronic kidney disease. Despite adult trials showing strong renal and cardiovascular benefits, pediatric studies are lacking because regulatory waivers excluded this population. Workshop participants emphasized urgent medical need, but also highlighted challenges: pediatric chronic kidney disease differs from adults, with congenital anomalies and nonglomerular disorders predominating, slower progression, and less proteinuria, limiting extrapolation from adult data. Safety concerns specific to children include dehydration, infections, and growth, bone, and neurodevelopmental effects. Lessons from adult trials underscore the need for pediatric-specific end points and biomarkers, including for cardiovascular outcomes. Recent regulatory actions, including the US Food and Drug Administration's mandate for pediatric empagliflozin studies, mark progress. Upcoming clinical trials (A Study to Find Out How EMPAgliflozin is Tolerated and if it Helps Children and Adolescents With Chronic KIDNEY Disease [EMPA-KIDNEY-Kids], Phase 3 Clinical Trial with Dapagliflozin in Chronic Kidney Disease in Adolescents and Young Adult Patients [DOUBLE-PROTECT] Alport) will require collaborative international efforts by the pediatric nephrology community to close the knowledge gap and ensure equitable access to renoprotective therapies for children with chronic kidney disease.