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Kidney Week

Abstract: PO1002

The SGLT2 Inhibitor Canagliflozin Reduces the Plasma Markers TNFR-1, TNFR-2, and KIM-1 in 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
  • Neal, Bruce, 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
  • 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 biomarkers known to predict kidney outcomes in patients with type 2 diabetes (T2D). We assessed the effect of the SGLT2 inhibitor canagliflozin (CANA) on TNFR-1, TNFR-2 and KIM-1 in CANVAS study participants to determine whether early changes were associated with subsequent kidney outcomes.

Methods

The CANVAS trial randomized participants with T2D at high cardiovascular risk to CANA or placebo (PBO). TNFR-1, TNFR-2 and KIM-1 were measured with immunoassays (proprietary multiplex assay performed by RenalytixAI, NY, USA) at baseline, and years 1, 3, and 6. Mixed effects models for repeated measures assessed the effect of CANA vs PBO on TNFR-1, TNFR-2 and KIM-1. The association between early change (baseline to year 1) for each of the 3 markers and the kidney outcome (40% eGFR decline, end-stage kidney disease, or renal death) was assessed using multivariable adjusted Cox regression.

Results

Among 2872/4330 (67%) CANVAS participants with available plasma samples at baseline and follow-up, median baseline TNFR-1, TNFR-2 and KIM-1 were 2559, 9612, and 108 pg/mL. Difference between CANA and PBO in TNFR-1, TNFR-2, and KIM-1 during follow-up were 2.8% (95%CI −3.4, −1.3; P<0.001), −1.9% (95%CI −3.5, −0.2; P=0.028) and −26.7% (−30.7, −22.7; P<0.001). Increases in TNFR-1 and TNFR-2, but not KIM-1, at year 1 were independently associated with a higher risk of the kidney outcome (Table).

Conclusion

CANA reduces TNFR-1, TNFR-2 and KIM-1 in patients with T2D at high cardiovascular risk. Early increases in TNFR-1 and TNFR-2 were independently associated with higher risk of kidney disease progression and have the potential to be pharmacodynamic markers of non-response to CANA.