Dapagliflozin in Patients With CKD With Fabry Disease

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been demonstrated to reduce proteinuria and disease progression in people with chronic kidney disease (CKD), but data in Fabry disease (FD) are scant. This prospective, multicenter study evaluated the 12-month effects of dapagliflozin 10 mg/dL on albuminuria, proteinuria, and renal function in patients with FD and albuminuric CKD.

Adults with FD and albuminuric CKD (estimated glomerular filtration rate [eGFR] ≥ 25 ml/min) despite stable enzyme replacement therapy (ERT) or migalastat and maximally tolerated dose of renin-angiotensin system inhibitors (RAS-i) were included. Proteinuria, urinary albumin-to-creatinine ratio (UACR), eGFR, and blood pressure were assessed 12 months before dapagliflozin initiation (T0), at treatment initiation (T1), and at 12-month follow-up (T2).

Sixteen patients were enrolled. After 12 months of dapagliflozin, UACR and 24-hour proteinuria decreased by 47.6% (300.1 [interquartile range, IQR: 106.5-856.1] mg/g [T1] vs. 142.5 [IQR: 60.7-415.7) mg/g [T2]; P = 0.01) and 22.2% (0.45 [IQR: 0.31-1.67] g/d [T1] vs. 0.35 [IQR: 0.18-1.42] g/d [T2]; P < 0.001), respectively. Mixed-effects model analysis confirmed the effect of dapagliflozin on reducing 24-hour proteinuria (P < 0.001), after adjustment for age, sex, eGFR, FD phenotype and ERT/migalastat treatments. eGFR remained stable (63.50 [SD: 25.13] ml/min per 1.73 m² [T1] vs. 64.31 [SD: 26.40] ml/min per 1.73 m² [T2]; P = 0.65), contrasting with annual decline (-5.63 [SE: 1.78] ml/min per 1.73 m²) during T0 to T1 period, adjusting for sex, age, FD phenotype, ERT/migalastat treatments and 24-hour proteinuria. Eight out of 9 fast renal progressor patients achieved an annual eGFR slope ≤ 3 ml/min during the T1 to T2 period.

this preliminary evidence shows that dapagliflozin was associated with reduction in albuminuria, proteinuria, and eGFR decline in patients with FD and albuminuric CKD receiving ERT or migalastat and RAS-i over 12 months.