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Abstract: TH-PO237

Multi-Marker Biomarker Panel Predicts Adverse Cardiovascular and Kidney Outcomes in People With Diabetes and Albuminuric CKD in the CREDENCE Trial

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Hansen, Michael K., Janssen Research & Development, LLC, Spring House, Pennsylvania, United States
  • Vaduganathan, Muthiah, Division of Cardiovascular Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States
  • Tefera, Eshetu, Janssen Research & Development, LLC, Spring House, Pennsylvania, United States
  • Yavin, Yshai, Janssen Research & Development, LLC, Spring House, Pennsylvania, United States
  • Sattar, Naveed, University of Glasgow BHF Glasgow Cardiovascular Research Centre, Glasgow, Glasgow, United Kingdom
  • L Heerspink, Hiddo Jan, Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, Netherlands
  • Januzzi, James, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
Background

Circulating biomarkers reflecting different mechanistic pathways may identify patients at greatest clinical risk and who may be most likely to benefit from sodium glucose co-transporter-2 inhibitors. We evaluated the prognostic value of 4 biomarkers (N-terminal pro–B-type natriuretic peptide [NT-proBNP], high sensitivity cardiac troponin T [hs-cTnT], insulin-like growth factor binding protein 7 [IGFBP7], and growth differentiation factor 15 [GDF15]) either alone or in combination in people with T2D and CKD.

Methods

Among 2,627 participants in the CREDENCE trial with available biomarker data, we created a multi-marker panel assigning 1 point for each elevated concentration of NT-proBNP, hs-cTnT, IGFBP7, and GDF15. Multivariable Cox regression analysis was used to examine the association with risk of cardiac and kidney outcomes using each biomarker alone or as a multi-marker panel compared to a base clinical model alone for each outcome.

Results

Among all participants at baseline, 61% had elevated levels of NT-proBNP >125 pg/mL, 69% had hs-cTnT ≥14 ng/L, 50% had IGFBP7 >122 ng/mL, and 77% had GDF15 >1800 pg/mL. Overall, 7%, 15%, 23%, 27%, and 28% had 0, 1, 2, 3, and 4 elevated biomarkers. Increasing numbers of elevated biomarkers independently predicted each outcome in a graded fashion (Figure). Canagliflozin consistently reduced outcomes across multi-marker scores (Pinteraction>0.20 for all).

Conclusion

Biomarkers of myocardial injury and remodeling are frequently abnormal in T2D and CKD and, when combined, may identify patients at the greatest risk of progressing to cardiovascular and kidney outcomes.