SGLT2 inhibitors for kidney protection in children: expanding horizons beyond endocrinology

For over two decades, kidney protection in children has relied on angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs), which present significant limitations. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially developed as antidiabetic agents, have demonstrated significant benefits in preserving kidney function in adults with chronic kidney disease (CKD), regardless of diabetes status. The pathophysiology of paediatric CKD differs from adult CKD, with congenital anomalies of the kidney and urinary tract (CAKUT) as the predominant cause. Extrapolating adult data to paediatric patients is challenging, though preliminary studies suggest SGLT2i may mitigate hyperfiltration-related damage, reduce proteinuria, and slow CKD progression, on top of RAS-blockers. Recent paediatric case series and small clinical trials have shown promising results, though larger controlled studies are needed to confirm efficacy and safety. The ongoing DOUBLE PRO-TECT Alport trial represents a significant step toward evaluating SGLT2i kidney protection in children. While current data suggest potential benefits, careful assessment of adverse effects such as euglycaemic ketoacidosis (EuDKA) and calcium phosphorus imbalances is crucial. This review aims to explore the mechanism of action, clinical evidence, and future perspectives of SGLT2i in paediatric CKD, highlighting their potential as a novel therapeutic strategy beyond diabetes management.