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Insulin-like Growth Factor Binding Protein-7 Predicts Renal and Cardiovascular Outcomes in the Canagliflozin Cardiovascular Assessment Study

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posted on 12.11.2020, 02:00 by James L. Januzzi Jr, Javed Butler, Naveed Sattar, Jialin Xu, Wayne Shaw, Norman Rosenthal, Michael Pfeifer, Kenneth W. Mahaffey, Bruce Neal, Michael K. Hansen
Objective: To analyze the association between concentrations of plasma insulin-like growth factor binding protein-7 (IGFBP7) with renal and cardiac outcomes among participants with type 2 diabetes and high cardiovascular risk.

Research Design and Methods: Associations between IGFBP7 levels and clinical outcomes were assessed among participants in the Canagliflozin Cardiovascular Assessment Study (CANVAS) with type 2 diabetes and high cardiovascular risk.

Results: Among CANVAS participants, 3577 and 2898 had IGFBP7 measured at baseline and 1 year, respectively. Per log-unit higher concentration, baseline IGFBP7 was significantly associated with the composite renal endpoint of sustained 40% reduction in eGFR, need for renal replacement therapy, or renal death (hazard ratio [HR]=3.51; P<0.001), and the composite renal endpoint plus cardiovascular death (HR=4.90; P<0.001); other outcomes including development or progression of albuminuria were also predicted by baseline IGFBP7. Most outcomes were improved by canagliflozin regardless of baseline IGFBP7; however, those with baseline concentrations ≥96.5 ng/mL appeared to benefit more from canagliflozin relative to first progression of albuminuria compared to those with lower baseline IGFBP7 (HR=0.64 vs 0.95; Pinteraction =0.003). Canagliflozin did not lower IGFBP7 concentrations by 1 year; however, at 1 year, higher IGFBP7 concentrations more strongly predicted the composite renal endpoint (HR=15.7; P<0.001). Patients with rising IGFBP7 between baseline to 1 year had the highest number of composite renal events.

Conclusions: Plasma IGFBP7 concentrations predicted renal and cardiac events among participants with type 2 diabetes and high cardiovascular risk. More data are needed regarding circulating IGFBP7 and progression of diabetic kidney disease and its complications.

Funding

The CANVAS trial was sponsored by Janssen Research & Development, LLC. Canagliflozin has been developed by Janssen Research & Development, LLC, in collaboration with Mitsubishi Tanabe Pharma Corporation. Technical editorial assistance was provided by Alanna Kahhan, ELS, of MedErgy, and was funded by Janssen Research & Development, LLC.

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