Strategies for the Development of Sodium-Glucose Cotransporter-2 Inhibitors for Kidney Protection in Pediatric Chronic Kidney Disease: Proceedings of a Workshop Meeting in July 2023

Abstract

Pediatric patients with chronic kidney disease (CKD) are treated with nonspecific therapies such as renin-angiotensin-aldosterone system inhibitors; however, there are no approved therapies to slow the progression of pediatric CKD across its diverse etiologies. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated efficacy in slowing the rate of decline in estimated glomerular filtration rate and CKD progression in adults. These therapies hold the promise of similar clinical benefit for pediatric patients with CKD by potentially delaying progression to kidney failure. However, clinical data informing the efficacy, safety, and dosing of these products in pediatric patients with CKD are lacking. To address this issue, a 1.5-day workshop was convened by the Kidney Health Initiative and NephCure, with participation from stakeholders that included regulators, National Institutes of Health representatives, trialists, clinicians and investigators, industry representatives, patient advocates, and caregivers. The goal of the workshop was to elucidate the challenges and strategize approaches to evaluate the use of SGLT2is in pediatric patients with CKD. To this end, presentations and discussions at the workshop focused on the data supporting the degree to which the course of CKD and expected treatment responses between adult and pediatric populations with CKD are similar, and hence, the degree to which, if any, data from the trials of SGLT2is in adults could be extrapolated to pediatric patients with CKD. Discussions also focused on trial design feasibility, end points, gaps in knowledge, and safety considerations for SGLT2is in pediatric CKD. The workshop proposed pathways to advance the evaluation of SGLT2is as therapeutic agents to treat glomerular and nonglomerular pediatric CKD while identifying remaining challenges and research priorities.