Kidney Week

Abstract: FR-PO1179

Differences in Plasma Proteomic Profiles between Patients with and without Type 2 Diabetes and CKD: New insights from DAPA-CKD

Session Information

• CKD: Mechanisms - 2
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• De la Rambelje, Mark Andre, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Mark Andre De la Rambelje, MSc

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

Niels Jongs, PhD

• Greasley, Peter J., AstraZeneca, Gothenburg, Sweden

Peter J. Greasley, PhD

• Ågren, Rasmus, AstraZeneca, Gothenburg, Sweden

Rasmus Ågren, PhD

• Hammarstedt, Ann, AstraZeneca, Gothenburg, Sweden

Ann Hammarstedt, PhD

• Sjostrom, David, AstraZeneca, Gothenburg, Sweden

David Sjostrom, MD, PhD

• Voors, Adriaan A., Universitair Medisch Centrum Groningen Afdeling Cardiologie, Groningen, Groningen, Netherlands

Adriaan A. Voors, MD

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

Hiddo Jan L. Heerspink, PhD

Group or Team Name

• DAPA-CKD Biomarker Committee.

Background

The pathophysiology of chronic kidney disease (CKD) in patients with and without type 2 diabetes (T2D) may share common and distinct pathways. To better understand potential pathophysiological differences between patients with CKD with or without T2D, we compared circulating protein profiles between these two groups.

Methods

We used baseline plasma samples and clinical data from 2485 patients with CKD with and without T2D from the phase 3, randomized, placebo-controlled DAPA-CKD trial. We used the Olink® Explore 3072 panel with 2941 unique proteins for obtaining biomarker profiles of patients with CKD. We cross-sectionally compared patients with vs. without T2D. Differentially abundance testing was performed using Wilcoxon rank-sum test. Pathway analysis was performed with ingenuity pathway analysis (IPA).

Results

The 2485 included patients had a similar eGFR, UACR, and diabetes distribution compared with the overall clinical trial population. Patients with T2D compared with those without T2D were older (64.8 vs. 56.8 years), had a higher eGFR (44.4 vs 41.8 mL/min/1.73m²), and a higher UACR (median 990 vs. 870 mg/g). Patients with T2D compared to those without had higher levels of adhesion G protein-coupled receptor G1, keratin 8, kidney injury marker-1, natriuretic peptide B and interleukin 6 with respectively significant (Bonferroni adjusted p-value < 0.05) fold changes of 2.39, 1.97, 1.74, 1.56, and 1.39. These differentially expressed proteins, along with others, were associated with atherosclerosis signaling and increased inflammation and immune system activity in those with vs without T2D and CKD.

Conclusion

Plasma proteomic profiles of patients with CKD and T2D were revealed to be related to atherosclerosis and increased inflammation and immune system activity compared to CKD patients without T2D. These findings may aid in identifying new treatment targets for patients with diabetic and non-diabetic CKD.

Funding

• Commercial Support – AstraZeneca