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Abstract: PO0988

Associations Between TNFR-1, TNFR-2, and KIM-1 with Kidney and Cardiovascular Outcomes: Results from the CANVAS Trial

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Sen, Taha, Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, Netherlands
  • Li, Jingwei, The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia
  • Neuen, Brendon Lange, The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia
  • Parikh, Chirag R., Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Coca, Steven G., Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Neal, Bruce, The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia
  • Perkovic, Vlado, The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia
  • de Zeeuw, Dick, Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, Netherlands
  • Mahaffey, Kenneth W., Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States
  • Hansen, Michael K., Janssen Research & Development, LLC, Spring House, Pennsylvania, United States
  • L Heerspink, Hiddo Jan, Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, Netherlands
Background

Tumor Necrosis Factor Receptor (TNFR)-1, TNFR-2 and Kidney Injury Molecule-1 (KIM-1) are blood-based biomarkers that are known to predict kidney outcomes in patients with diabetic kidney disease. We sought to examine the association of baseline TNFR-1, TNFR-2 and KIM-1 with cardiovascular (CV) and kidney outcomes in patients with type 2 diabetes mellitus (T2DM) in the CANagliflozin cardioVascular Assessment Study (CANVAS) study, and secondly, whether these markers modified the effect of the SGLT2 inhibitor canagliflozin (CANA) on these outcomes.

Methods

The CANVAS trial randomized participants with T2DM at high CV risk to CANA or placebo. Plasma TNFR-1, TNFR-2 and KIM-1 were measured with immunoassays (proprietary multiplex assay performed by RenalytixAI, NY, USA). Associations between the 3 biomarkers and the CV (nonfatal myocardial infarction, stroke, or CV death) and kidney outcome (40% eGFR decline, end-stage kidney disease, or renal death) were assessed using multivariable adjusted Cox regression.

Results

We included 3548 (82% of original cohort of 4330) CANVAS participants with available baseline plasma samples (mean age 62.8 y, 33.0% female, mean eGFR 76.9 mL/min/1.73 m2, median uACR 11.6 mg/g, median TNFR-1, TNFR-2 and KIM-1: 2578 pg/mL, 9684 pg/mL, and 110 pg/mL). During a mean follow-up of 5.6 y, 554 CV and 137 kidney outcomes occurred. After adjustment for demographics and clinical characteristics, each doubling of baseline TNFR-1, TNFR-2, KIM-1 was significantly associated with higher risk of kidney outcomes: TNFR-1, HR 3.74 (95% CI 2.28, 6.15); TNFR-2, HR 2.68 (95% CI 2.01, 3.57); KIM-1, HR 1.50 (95% CI 1.23, 1.82). The biomarkers were not associated with the CV outcome. The protective effect of CANA on the CV and kidney outcome (HR 0.56, 95% CI 0.40, 0.78) was consistent regardless of baseline TNFR-1, TNFR-2, or KIM- 1 (all P-interaction>0.10).

Conclusion

Higher levels of TNFR-1, TNFR-2 and KIM-1 were independently associated with a higher risk of kidney but not CV outcomes in patients with T2DM at high CV risk. The baseline markers did not modify the effect of CANA on these outcomes.

Funding

  • Commercial Support –