Outcomes included 24-hour proteinuria, eGFR trajectories, tolerability, and predictors of response. The team used generalized mixed effects models for proteinuria and linear mixed effects models for eGFR, with each patient serving as their own control.

The 101 patients had a median age of 52 years (interquartile range [IQR], 31-60), and 47.5% were men. Of the 77 patients with genetic confirmation, 45.5% had X-linked inheritance, 31% autosomal dominant, and 7% autosomal recessive. Dapagliflozin was used in 85.8% of patients and empagliflozin in 14.2%.

SGLT2 Inhibitors, Proteinuria, and eGFR in Alport Syndrome

Among 61 patients with complete proteinuria data, median proteinuria rose from 1.2 g/day (IQR, 0.7-2.4) 12 months before treatment to 1.5 g/day (IQR, 0.9-2.6) at SGLT2 inhibitor initiation.¹ After initiation, the trend reversed. Proteinuria fell to 1.26 g/day (IQR, 0.7-2.0) at 6 months and was 1.35 g/day (IQR, 0.6-2.4) at 12 months, a 10% reduction (P = .04).

Men had higher proteinuria, but the proteinuria response did not differ by sex (P = .39 for interaction). Body mass index (BMI), albumin, and genetic background were not associated with response.

Among 72 patients with complete eGFR data, median eGFR declined from 59 mL/min/1.73 m² (IQR, 40-90) 12 months before treatment to 52 mL/min/1.73 m² (IQR, 38-80) at initiation. It was 47 mL/min/1.73 m² (IQR, 33-74) at 6 months and 49 mL/min/1.73 m² (IQR, 31-73) at 12 months. Pre- and post-treatment eGFR trajectories did not differ significantly (P = .79).

Sex did modify eGFR trajectories (P = .03 for interaction): women showed partial recovery, and men showed persistent decline. BMI also modulated eGFR response, while dyslipidemia, albumin, and genetic background did not. No serious adverse events led to discontinuation.

Prospective SGLT2 Inhibitor Trials Needed in Alport Syndrome

The investigators concluded that the findings support SGLT2 inhibitors as add-on nephroprotection for adults with Alport syndrome on RAAS blockade.¹ In his interview, Santoro framed the data more cautiously.

“This finding should be considered hypothesis generating and does not establish a causal or sustained kidney protective effect,” Santoro said.

He said prospective controlled studies are needed to determine long-term benefit. They should also test whether the effect differs by genotype, sex, mode of inheritance, and disease stage.

“Until a few years ago, we had just one treatment for patients with Alport syndrome,” Santoro said. “This is a hope for patients with Alport syndrome to have another option, another treatment.”

Editor’s Note: Santoro reported no relevant disclosures.

ReferencesSantoro D; GLIFAS Group. SGLT2 inhibitors in Alport syndrome: a national multicenter study (GLIFAS). Abstract SA-OR075. Presented at: American Society of Nephrology Kidney Week 2026; October 21-25, 2026; Denver, CO. doi:10.1681/ASN.2026mh3dxkvtBoeckhaus J, Gale DP, Simon J, et al. SGLT2-inhibition in patients with Alport syndrome. Kidney Int Rep. 2024;9(12):3490-3500. doi:10.1016/j.ekir.2024.09.014Toso D, Cinquina V, Ritelli M, et al. Sodium-glucose cotransporter-2-inhibitors in adult patients with Alport syndrome. Kidney Int Rep. 2026;11(5):106417. doi:10.1016/j.ekir.2026.106417