<b>Objective</b>:
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.
<p><b>Research
Design and Methods</b>: 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. </p>
<p><b>Results</b>:
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; <i>P</i><0.001), and the
composite renal endpoint plus cardiovascular death (HR=4.90; <i>P</i><0.001); other outcomes including
development or progression of albuminuria were also predicted by baseline
IGFBP7. <a>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; <i>P</i><sub>interaction </sub>=0.003).
</a>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; <i>P</i><0.001).
Patients with rising IGFBP7 between baseline to 1 year had the highest number
of composite renal events. </p>
<p><b>Conclusions</b>:
<a>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. </a></p>