Dapagliflozin in Patients With CKD With Fabry Disease

Area of Science:

• Nephrology
• Genetics
• Pharmacology

Background:

• Sodium-glucose cotransporter 2 (SGLT2) inhibitors are known to reduce proteinuria and slow disease progression in chronic kidney disease (CKD).
• Data on the effects of SGLT2 inhibitors in Fabry disease (FD), a rare genetic disorder, are limited.
• Fabry disease patients often develop albuminuric CKD, necessitating effective treatment strategies.

Purpose of the Study:

• To evaluate the 12-month efficacy of dapagliflozin in reducing albuminuria, proteinuria, and preserving renal function in patients with Fabry disease and albuminuric CKD.
• To assess the impact of dapagliflozin on estimated glomerular filtration rate (eGFR) decline in this specific patient population.

Main Methods:

• A prospective, multicenter study included adult patients with FD and albuminuric CKD on stable enzyme replacement therapy (ERT) or migalastat and maximally tolerated renin-angiotensin system inhibitors (RAS-i).
• Dapagliflozin 10 mg was administered, and urinary albumin-to-creatinine ratio (UACR), 24-hour proteinuria, and eGFR were measured at baseline and 12 months.
• Statistical analyses, including mixed-effects models, were used to evaluate treatment effects and compare eGFR changes.

Main Results:

• After 12 months, dapagliflozin significantly reduced UACR by 47.6% and 24-hour proteinuria by 22.2%.
• eGFR remained stable during the dapagliflozin treatment period, contrasting with a significant decline observed prior to treatment.
• Eight out of nine patients identified as fast renal progressors achieved an eGFR slope of ≤ 3 ml/min per year with dapagliflozin treatment.

Conclusions:

• Dapagliflozin demonstrated a significant reduction in albuminuria and proteinuria in patients with FD and albuminuric CKD.
• The study provides preliminary evidence that dapagliflozin may help stabilize renal function and reduce eGFR decline in this patient group.
• These findings suggest a potential therapeutic role for SGLT2 inhibitors in managing kidney disease in Fabry disease.