2025 Volume 66 Issue 4 Pages 540-546
Growth differentiation factor-15 (GDF-15), a member of the TGF-beta superfamily, is upregulated in response to tissue ischemia and proinflammatory cytokines that promote the onset and progression of atherosclerosis. Given that GDF-15 is also elevated in individuals with kidney dysfunction compared to those without, GDF-15 levels may contribute to pathways that play a role in chronic kidney disease-associated atherosclerosis.
In 338 patients with coronary artery disease, we investigated the association between GDF-15 and plaque morphology assessed by intravascular ultrasound. No association was found between log-transformed GDF-15 levels and the percentage of calcified plaque volume in chronic kidney disease (CKD) stages G1-G2 (r = 0.077, P = 0.328) or G3a (r = 0.012, P = 0.910). In contrast, a significant association was observed in stages G3b-G5 (r = 0.275, P < 0.001).
Multiple linear regression analysis showed that the highest GDF-15 tertile (≥ 2,567 ng/L) as a categorical variable and GDF-15 levels were associated with the calcified plaque percentage in the CKD stages G3b-G5 (n = 82, Estimate [95% confidence interval], 0.0038 [0.0004, 0.0071]; P = 0.0027). This association was also observed with GDF-15 as a continuous variable (estimate per 2-fold higher, 0.0128 [0.0028, 0.2281]; P = 0.0013). No association was found for other CKD stages.
A significant association was found between elevated GDF-15 levels and the presence of calcified coronary plaques, as assessed by intravascular ultrasound, in patients with coronary artery disease and CKD.
