Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder characterized by globotriaosylceramide (Gb3) accumulation, resulting in kidney and cardiac dysfunction. Although enzyme replacement therapy (ERT) and chaperone therapy are the standard therapies, progression of renal decline persists. Sodium-glucose co-transporter 2 (SGLT2) inhibitors exert renoprotective effects in chronic kidney disease (CKD), but their efficacy in FD remains unknown.
Methods: We retrospectively analyzed data of 10 patients with FD treated with SGLT2 inhibitors and compared their renal outcomes to 18 patients with CKD without FD. The estimated glomerular filtration rate (eGFR) slope, urinary albumin-to-creatinine ratio (UACR), and plasma brain natriuretic peptide (BNP) levels were assessed 1 year before and after initiating SGLT2 inhibitor therapy. Linear mixed-effects models were employed for statistical analysis.
Results: In patients with FD, the annual eGFR decline significantly improved from -4.38 mL/min/1.73 m2/year (IQR: -10.57 to 0.59) before treatment to 1.25 (IQR: -4.16 to 9.74) after treatment (p < 0.05). This improvement remained significant after adjusting for confounding factors. In contrast, the annual eGFR decline in patients with CKD without FD also tended to improve, albeit without significance. Notably, the initial eGFR decline usually seen with SGLT2 inhibitors in CKD was not observed in the FD cohort. UACR and plasma BNP levels remained unchanged after SGLT2 inhibitor therapy.
Conclusions: SGLT2 inhibitors substantially attenuated the decline in eGFR in patients with FD. These findings support their potential as a renoprotective adjunct in the management of FD.
Keywords: Chronic kidney disease; Fabry disease; Sodium–glucose co-transporter 2 inhibitors; eGFR slope.
© 2025 The Authors.