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Abstract: SA-OR28

Circulating Metabolites to Predict Renal Outcomes in CANVAS Type 2 Diabetes Mellitus Population

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Darshi, Manjula, Janssen Research & Development, LLC, Boston, Massachusetts, United States
  • Tefera, Eshetu, Janssen Research & Development, LLC, Spring House, Pennsylvania, United States
  • Gao, Bin, Janssen Research & Development, LLC, Spring House, Pennsylvania, United States
  • Weidner-Wells, Michele, Janssen Research & Development, LLC, Spring House, Pennsylvania, United States
  • Reilly, Dermot F., Janssen Research & Development, LLC, Boston, Massachusetts, United States
  • Coorey, Craig, School of Medicine, Western Sydney University, Sydney, New South Wales, Australia
  • Tang, Owen, Charles Perkins Centre, The University of Sydney; Dept of Cardiology, Royal North Shore Hospital; Cardiovascular Discovery Group, Kolling Institute of Medical Research, The University of Sydney; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
  • Yang, Jean, Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia
  • Neal, Bruce, The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia
  • Arnott, Clare Gabrielle, The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia
  • Mahaffey, Kenneth W., Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States
  • Perkovic, Vlado, The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia
  • Hansen, Michael K., Janssen Research & Development, LLC, Spring House, Pennsylvania, United States
  • Ferrannini, Ele, Institute of Clinical Physiology, National Research Council, Pisa, Italy
  • Figtree, Gemma, Charles Perkins Centre, The University of Sydney; Dept of Cardiology, Royal North Shore Hospital; Cardiovascular Discovery Group, Kolling Institute of Medical Research, The University of Sydney; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
Background

Albuminuria and eGFR are biomarkers for kidney disease progression but fail to explain all future risk. Additional biomarkers that better represent underlying disease pathophysiology may improve the prediction of progression from chronic kidney disease (CKD) to end stage renal disease (ESRD). We examined if baseline plasma metabolites predict renal outcomes in the Canagliflozin Cardiovascular Assessment Study (CANVAS) participants.

Methods

Plasma metabolites were assayed from a subset of the CANVAS study participants by HPLC (HILIC)-mass spectrometry using targeted assays. Forty-two metabolites were analyzed for association with the renal outcome (40% eGFR decline, end-stage kidney disease, or renal death) using Cox regression.

Results

We included 967 (22%) of the 4,330 CANVAS participants comprising 341 females (35%), mean age 63 ± 8 years, and BMI 33 ± 5 kg/m2. All patients had T2DM with mean HbA1c 8.2 ± 0.9%, eGFR 75.5 ± 18.3 mL/min/1.73m2, and median ACR (1Q, 3Q) 11.89 (6.5, 37.49). During a median follow-up of 5.6 years, 63 (6.5%) patients experienced a renal event. There were 10 metabolites significantly associated with the renal outcome (all P <0.05) when adjusted for age and gender (Figure) and treatment effect. In a fully adjusted model (age, gender, race, BMI, HbA1c, cholesterol, blood pressure, history of heart failure, baseline ACR and eGFR), arginine alone remained significant (P = 0.01).

Conclusion

Lower baseline plasma arginine levels are independently associated with high risk for renal events in patients with T2DM.

Funding

  • Commercial Support