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Kidney Week

Abstract: TH-PO1117

SGLT2 Inhibition in Alport Syndrome: First Large-Scale Trial to Plan a Randomized Controlled Trial in Children

Session Information

  • Late-Breaking Posters
    November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1900 Pediatric Nephrology

Authors

  • Gross, Oliver, Universitatsmedizin Gottingen, Goettingen, Niedersachsen, Germany
  • Boeckhaus, Jan, Universitatsmedizin Gottingen, Goettingen, Niedersachsen, Germany

Group or Team Name

  • For the GuARd Alport investigators, International Alport Alliance
Background

Trials with >10,000 patients showed positive outcomes of SGLT2is in elderly patients with CKD. These trials included no children and no young adults with Alport syndrome (AS).

Methods

This multicenter, international study (NCT02378805) assessed 99 patients with AS from 12 countries after start of SGLT2i at early CKD-stages.

Results

Mean age of children (n=10) was 16 years (range 9 to 17), eGFR >90ml/min/1.73qm, and UAPR was >1.0g/gCrea. Only adults with in-label use of SGLT2i (n=89) were analyzed. At baseline, mean age was 37±14 years, eGFR 63±35 ml/min/1.73qm, and albuminuria (UACR) 1822±1484 mg/g creatinine. Because of country- and center-specific different routines and visit intervals, all data are compared to baseline (fig. 1). At V1 month 1 to 3, UACR decreased by 34% (p<0.001), and eGFR dropped by 6% (p=0.05). At V2 (mean 5.7 months), UACR dropped by 29% (p=0.003), as did eGFR by 6% (p<0.001). At V3 (11.7 months), UACR dropped by 24%, and eGFR did by 15% (n=26; p=0.001). BMI decreased from 27.8±6.3 to 27.2±6 kg/qm and serum albumin increased (3.8±0.7 vs 3.9±0.4 g/dL). Blood pressure decreased slightly from 127/82 to 126/80 mmHg. At V4 (21 months), UACR dropped by 27%, and eGFR did by 10% (n=12; p=0.02). Compared to baseline, eGFR slope changed from -13.6 (V1), -8.4 (V2), -7.7 (V3), to -4.1 ml/min/year at V4.
At a total of 50 patient-years at risk, adverse drug reactions occurred in 7/66 patients (11%).

Conclusion

For the first time, the effect of SGLT2i in a large number of young patients with AS was investigated: patients were much younger than non-diabetic CKD patients in EMPA-Kidney (37 vs. 64 years), had a similar BMI and blood pressure, a much better eGFR (63 vs. 39 ml/min/qm), and a four times higher UACR (1822 vs. 461 mg/gCrea). Patients with AS showed an intermediate response in UACR reduction. In month 12 and 21, the positive effect on long-term eGFR slope is still inconclusive. For that reason, efficacy and safety of SGLT2i in children will be addressed in the upcoming first Pediatric RCT, DOUBLE PRO-TECT Alport (NCT05944016).

Funding

  • Government Support - Non-U.S.