Kidney Week

Abstract: TH-PO1053

Cumulative Effects of Aldosterone Synthase and SGLT2 Inhibition on Albuminuria in People with CKD

Session Information

• CKD: Therapeutic Advances
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Rossing, Peter, Steno Diabetes Center Copenhagen, Herlev, Capital Region of Denmark, Denmark

Peter Rossing, MD, DrMed

• Hauske, Sibylle Jenny, Boehringer Ingelheim International GmbH, Ingelheim, Rheinland-Pfalz, Germany

Sibylle Jenny Hauske, DrMed

• Cronin, Lisa, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, United States

Lisa Cronin, DrMed, MD, MS, MSc

• Heerspink, Hiddo Jan L., University Medical Centre Groningen, Groningen, Netherlands

Hiddo Jan L. Heerspink, PhD

• Meyerhoff, Juliane, Boehringer Ingelheim International GmbH, Ingelheim, Rheinland-Pfalz, Germany

Juliane Meyerhoff, PhD

• Shah, Shimoli, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, United States

Shimoli Shah, MD

• Sun, Zhichao, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, United States

Zhichao Sun, PhD

• de Zeeuw, Dick, University Medical Centre Groningen, Groningen, Netherlands

Dick de Zeeuw, MD, PhD

• Tuttle, Katherine R., Providence Inland Northwest Health, Spokane, Washington, United States

Katherine R. Tuttle, MD, FASN

Group or Team Name

• On behalf of the ASi in CKD Group.

Background

A phase II trial reported efficacy and safety of the aldosterone synthase inhibitor (ASi) BI 690517 in chronic kidney disease (CKD) showing significant albuminuria reduction with or without empagliflozin (EMPA) in the background. This post hoc analysis estimates the cumulative effects of ASi and EMPA 10mg on urine albumin:creatinine ratio (UACR) vs ASi alone.

Methods

Participants receiving a maximally tolerated dose of a renin-angiotensin system inhibitor were first randomized (R1) to an 8-week run-in period to receive EMPA 10mg daily or EMPA_PBO, followed by a second randomization (R2) to a 14-week treatment period to receive ASi (3, 10, or 20mg daily) or ASi_PBO. For the run-in period, EMPA effects were assessed by pooling participants into EMPA vs EMPA_PBO groups, regardless of ASi dose levels at R2. Randomized ASi dose groups on top of EMPA/EMPA_PBO were assessed from R2 to 14 weeks. R2 served as the baseline reference time point and mixed-effect model for repeated measures (MMRM) was used to assess change in UACR. Cumulative effects of both ASi and EMPA were calculated by adding UACR changes from R1 to R2 and R2 to the end of treatment period.

Results

UACR data were available from 249 participants who were randomized at R1 to receive EMPA 10mg and 254 who received EMPA_PBO. Estimated cumulative effects on UACR reduction from R1 to week 14 were larger with EMPA+ASi 10mg (-61%) compared to ASi 10mg alone (-40%) and vs EMPA_PBO+ASi_PBO (-3%) (Table).

Conclusion

Meaningfully larger UACR reductions across all ASi doses were achieved in participants with CKD who received both active components of EMPA+ASi compared to treatment with either ASi or EMPA alone. Combination of ASi with SGLT2 inhibitors is a promising, novel therapy strategy that may afford superior benefits over AS or SGLT2 inhibition alone and will be tested further in a phase III clinical trial.

Funding

• Commercial Support – Boehringer Ingelheim

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.202455w7qxng