Abstract: SA-OR075
SGLT2 Inhibitors in Alport Syndrome: A National Multicenter Study (GLIFAS)
Session Information
- Late-Breaking Research Orals: Pediatrics, Genetics, and Glomerular Diseases
October 24, 2026 | Location: Four Seasons Ballroom 2, Convention Center
Abstract Time: 04:54 PM - 05:06 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)
Author
- Santoro, Domenico, Universita degli Studi di Messina, Messina, Sicily, Italy
Group or Team Name
- GLIFAS Group
Background
Alport syndrome (AS) is a collagen IV nephropathy caused by pathogenic COL4A3–5 variants. Despite renin–angiotensin–aldosterone system blockade (RAASb), residual proteinuria often persists. We assessed the 12-month effects of sodium–glucose cotransporter 2 inhibitors (SGLT2i) in AS.
Methods
This longitudinal observational study enrolled adults with genetically and/or histologically confirmed AS from 16 Italian centers. Eligibility criteria were eGFR 20–90 mL/min/1.73 m2, proteinuria 300–5000 mg/day, and ongoing RAASb. Data were collected 12 months before SGLT2i initiation (T−12), at baseline (T0), and at 6- and 12-month time points. Outcomes included 24-hour proteinuria, eGFR trajectories, tolerability, and response predictors. Generalized and linear mixed-effects models assessed proteinuria and eGFR, respectively.
Results
We enrolled 101 patients (median age 52 [31–60] years; 47.5% male). Genetic confirmation was available in 77 patients; inheritance was X-linked in 45.5%, autosomal dominant in 31%, and autosomal recessive in 7%. Dapagliflozin and empagliflozin were used in 85.8% and 14.2% of cases, respectively.
Among 61 patients with complete proteinuria data, proteinuria increased from 1.2 [0.7–2.4] g/day at T−12 to 1.5 [0.9–2.6] at T0. After SGLT2i initiation, the trend changed significantly, decreasing to 1.26 [0.7–2.0] at 6 months and stabilizing at 1.35 [0.6–2.4] at 12 months (10% reduction; p=0.04;) (Figure 1 A). Males had higher proteinuria, but response did not differ by sex (interaction p=0.385) (Figure 1 B). BMI, albumin, and genetic background were not associated with response.
Among 72 patients with complete eGFR data, eGFR declined from 59 [40–90] mL/min/1.73 m2 at T−12 to 52 [38–80] mL/min/1.73 m2 at T0, and was 47 [33–74] mL/min/1.73 m2 and 49 [31–73] mL/min/1.73 m2 at 6 and 12 months, respectively (Figure 2A). Pre- and post-treatment trajectories did not differ (p=0.791). Sex modified eGFR trajectories (interaction p=0.028), with partial recovery in females and persistent decline in males (Figure 2B). BMI modulated eGFR response, whereas dyslipidemia, albumin, and genetic background did not. No serious adverse events led to discontinuation.
Conclusion
In adults with AS receiving RAASb, SGLT2i reduced proteinuria and stabilized kidney function over 12 months, supporting their use as add-on nephroprotection.
Acknowledgment
We thanks all the partecipants of GLIFAS STUDY