Inflammation, metalloproteinases, and growth factors in the development of carotid atherosclerosis in renal transplant patients.

BACKGROUND

Cardiovascular disease is the leading cause of death in renal transplant (RT) patients. Both traditional and emerging risk factors, some of which are controversial, have been described in the pathogenesis of cardiovascular disease. Carotid ultrasound (CUS) is considered to be an excellent diagnostic tool for subclinical atherosclerosis.

OBJECTIVE

To evaluate the relationship between biomarkers of inflammation, growth factors, metalloproteinases, and the development of subclinical atherosclerosis diagnosed by using CUS.

METHODS

We studied 93 RT patients (aged 54±12 years; 67.9% men; 13.5% with pre-RT diabetes mellitus). The following biomarkers were determined in the patients' blood hours before RT: C-reactive protein (CRP) and serum amyloid A using nephelometry; interleukin (IL) 2, 6, 8, and 10 and soluble IL-2 receptor, tumor necrosis factor (TNF) α, vascular endothelial growth factor (VEGF), epidermal growth factor, and monocyte chemotactic peptide using chemoluminescence; and pregnancy-associated plasma protein (PAPP)A using ELISA. A CUS was carried out during the first month after RT.

RESULTS

Carotid intima-media thickness (IMT) was elevated in 51% of the patients, and 50.5% of the patients had atherosclerotic plaque. Both plaque (P=.004) and IMT (P=.001) correlated with age, and the increase of IMT was progressive, on both the left and the right side. Pre-RT CRP, IL-8, TNF-α, VEGF, MCP-1, and PAPP-A were significantly more elevated in patients with plaque. In the multivariate analysis adjusted for clinical variables, age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.10; P=.04), CRP (OR, 7.5; 95% CI, 2.05-27.3; P=.002), IL-8 (OR, 4.73; 95% CI, 1.27-17.6; P=.02), and PAPP-A (OR, 4.45; 95% CI, 1.22-16.2; P=.023) were independent markers of the presence of plaque.

CONCLUSIONS

Age, CRP, IL-8, and PAPP-A, and not growth factors, are markers of carotid atheromatous plaque in RT patients.