Kidney Week

Abstract: TH-OR038

Canagliflozin Induced Reduction in TNF Receptor 1 Is Associated with a Reduction in eGFR Decline

Session Information

• Diabetic Kidney Disease Trials: Progress Being Made
  October 25, 2018 | Location: 5A, San Diego Convention Center
  Abstract Time: 05:54 PM - 06:06 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Lambers Heerspink, Hiddo Jan, University of Groningen, Groningen, Netherlands

Hiddo Jan Lambers Heerspink, PhD



• Perco, Paul, Medical University of Innsbruck, Innsbruck, Austria

Paul Perco,

• Mulder, Skander, University of Groningen, Groningen, Netherlands

Skander Mulder,

• Leierer, Johannes, Medical University of Innsbruck, Innsbruck, Austria

Johannes Leierer,

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

Michael K. Hansen,

• Heinzel, Andreas, emergentec biodevelopment GmbH, Vienna, Austria

Andreas Heinzel,

• Mayer, Gert J., Medical University of Innsbruck, Innsbruck, Austria

Gert J. Mayer,

Background

Circulating levels of the pro-inflammatory biomarker Tumor Necrosis Factor Receptor 1 (TNFR1) predict the risk of end-stage renal disease (ESRD) in patients with type 2 diabetes. Experimental studies suggested that sodium glucose co-transporter 2 (SGLT2) inhibitors exert anti-inflammatory effects. Here we examined the effect of the SGLT2 inhibitor canagliflozin (CANA) on TNFR1 and assessed whether the change in TNFR1 is associated with eGFR decline.

Methods

TNFR1 levels were measured at baseline, 52 and 104 weeks in plasma samples of 297 patients with type 2 diabetes and urinary albumin:creatinine ratio >15 mg/g participating in a phase 3 clinical trial. Patients were randomly assigned to CANA 100 or 300 mg or glimepiride (GLIM) uptitrated to 6 to 8 mg. Repeated measure models were used to compare effects of CANA vs. GLIM on TNFR1 over 104 weeks follow-up and to assess associations between change in TNFR1 with eGFR change.

Results

During 104 weeks of follow-up, TNFR1 increased in the GLIM group but stabilized or decreased in the CANA 100 and 300 mg groups. Compared with glimepiride, treatment with CANA 100 and 300 mg dose-dependently decreased TNFR1 by 5.9% (1.3 to 10.3; p=0.013) and 9.2% (4.7 to 13.5%; p<0.001). The change in TNFR1 at week 52 (the earliest available time point) was significantly and independently associated with eGFR decline during 104 weeks follow-up (p=0.0234). In increasing tertiles of TNFR1 change, eGFR change during 104 weeks follow-up was -0.4 (95%CI -2.3 to 1.5), -4.7 (95%CI -6.5 to -2.8), and -7.1 (95%CI -9.0 to -5.2) ml/min/1.73m². Reductions in HbA1c were similar with GLIM and CANA during follow-up.

Conclusion

The reduction in TNFR1 with CANA and association between changes in TNFR1 and eGFR suggests that TNFR1 may be used to monitor effects of CANA on long-term kidney function.

Funding

• Commercial Support –