Kidney Week

Abstract: TH-OR52

Association of Urinary Epidermal Growth Factor with Kidney Outcomes and Effects of SGLT2 Inhibition: Results from the CANVAS and CREDENCE Trials

Session Information

• Diabetic Kidney Disease - Clinical: Novel Insights into Precision Medicine
  October 24, 2024 | Location: Room 33, Convention Center
  Abstract Time: 05:30 PM - 05:40 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Moedt, Erik, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Erik Moedt, PharmD, MSc

• Koshino, Akihiko, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Akihiko Koshino, MD

• Jongs, Niels, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Niels Jongs, PhD

• Ju, Wenjun, University of Michigan Department of Internal Medicine, Ann Arbor, Michigan, United States

Wenjun Ju, PhD

• Hansen, Michael K., Janssen Research and Development LLC, Spring House, Pennsylvania, United States

Michael K. Hansen, PhD

• Arnott, Clare Gabrielle, The George Institute for Global Health, Sydney, New South Wales, Australia

Clare Gabrielle Arnott, MBBS, PhD

• Neal, Bruce, The George Institute for Global Health, Sydney, New South Wales, Australia

Bruce Neal

• Bakker, Stephan J.L., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Stephan J.L. Bakker, MD, PhD

• Heerspink, Hiddo Jan L., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Hiddo Jan L. Heerspink, PhD

Background

Epidermal growth factor (EGF) is involved in the regenerative processes of kidney tubular cells. Higher urinary EGF (uEGF) levels are associated with a reduced risk of kidney failure in observational studies. The SGLT2 inhibitor canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes (T2D). We investigated the association of uEGF with kidney outcomes and assessed the effect of canagliflozin on uEGF.

Methods

We performed a post-hoc analysis of the combined CANVAS and CREDENCE trials, which assessed efficacy and safety of canagliflozin versus placebo in those with T2D +/- albuminuric chronic kidney disease. The primary outcome was defined as a 40% decline in eGFR, kidney failure, or death due to kidney failure. Hazard ratios were estimated using multivariate Cox regression. We examined the effect of canagliflozin 100 mg/d on change from baseline in uEGF at years 1 and 3 in 2038 CREDENCE patients (year 3 CANVAS samples were not available) using a repeated measures model.

Results

We analyzed data for 3521 (81.3% of the total cohort) CANVAS patients (mean age 62.8 years, eGFR 77.0 mL/min/1.73m², median UACR 11.6 mg/g) and 2457 (55.8% of the total cohort) CREDENCE patients (mean age 63.2 years, eGFR 57.0 mL/min/1.73m², median UACR 918 mg/g), with available urine samples. Every doubling in baseline uEGF/Cr was associated with a reduced risk of the kidney outcome (HR 0.86 [95% CI 0.79, 0.93]; p<0.001). This association was consistent across baseline eGFR and UACR subgroups. The uEGF/Cr change from baseline to year 1 was -12.5% ([95% CI -15.6, -9.1]; p<0.001) in the placebo group and -5.4% ([95% CI -8.7, -1.9]; p=0.002) in the canagliflozin group, corresponding to a between-group difference of 8.1% ([95% CI 1.1, 15.6]; p=0.016). The effect of canagliflozin on uEGF was more pronounced at week 156 with a between-group difference of 16.5% ([95% CI 2.1, 32.8]; p=0.016).

Conclusion

Higher baseline uEGF/Cr was significantly associated with lower risk of kidney disease progression in patients with T2D with and without CKD. Canagliflozin consistently attenuated the uEGF/Cr decrease compared to placebo.

Funding

• Commercial Support – Janssen