SGLT2 Inhibition in Young Patients with Alport Syndrome, with Oliver Gross, MD

Study results presented at the American Society of Nephrology Kidney Week 2023 provided the first data for the effect of SGLT2 inhibition in a younger patient population with Alport syndrome, highlighting an intermediate response in albuminuria reduction from baseline to the end of the treatment period.

The noninterventional, observational study enrolled 99 patients, including 10 children and 89 adults, with Alport syndrome from 12 countries following the initiation of SGLT2 inhibitors during early stages of chronic kidney disease (CKD). Of note, only adults with in-label use of SGLT2i were able to be included in the present study.

Among adult participants, the mean age was 37±14 years, mean estimated glomerular filtration rate (eGFR) was 63±35 ml/min/1.73qm, and mean albuminuria was 1822±1484 mg/g creatinine. At the first visit, which took place between months 1 and 3 of treatment, albuminuria decreased by 34% (P < .001) and eGFR decreased by 6% (P = .05). At visit 2, a mean duration of 5.7 months into treatment, albuminuria was reduced by 29% (P = .003) and eGFR decreased by 6% (P < .001).

Investigators pointed out albuminuria and eGFR continued to decrease at visit 3 (mean, 11.7 months of treatment), lowering by 24% and 15%, respectively (n = 26; P = .001). Additionally, BMI decreased from 27.8±6.3 to 27.2±6 kg/m2, serum albumin increased from 3.8±0.7 to 3.9±0.4 g/dL, and blood pressure decreased from 127/82 to 126/80 mmHg.

At the fourth and final visit (mean, 21 months of treatment), albuminuria was reduced by 27% and eGFR was reduced by 10% (n = 12; P = .02). Compared to baseline, eGFR slope changed from -13.6 at visit 1, -8.4 at visit 2, -7.7 at visit 3, to -4.1 ml/min/year at visit 4. Although participants showed an intermediate response in albuminuria reduction, the positive effect on long-term eGFR slope remained inconclusive at months 12 and 21. Adverse drug reactions occurred in 7 (11%) patients at a total of 50 patient-years at risk.

The editorial team of HCPLive Nephrology sat down with Oliver Gross, MD, of the department of nephrology and rheumatology at the University of Göttingen Medical Center, for further insight into the unmet need in Alport syndrome, the results of the trial, and what they add to what is already known about SGLT2 inhibition in patients with CKD.

Gross has no relevant disclosures of interest.

Reference:

1. Gross O, Boeckhaus J. SGLT2 Inhibition in Alport Syndrome: First Large-Scale Trial to Plan a Randomized Controlled Trial in Children. Paper Presented at: American Society of Nephrology Kidney Week 2023. November 1-5, 2023.