PP.13.18

Abstract

Objective: Recent evidence suggests that renal vascular changes contribute to progressive renal disease and that alteration of vascular endothelial growth factor-A (VEGF-A) might play an important role in modulating microvascular loss of macrovascular remodeling in the kidney, as well as in the vessels. It remains controversial the mechanism by which VEGF works in the kidney, as well as in the vessels at least in the early stages of chronic kidney disease (CKD). Whether VEGF-A is detrimental in early stages of CKD or whether in other renal conditions has not yet been clearly answered. Tissue inhibitor of metalloproteinase -1 (TIMP-1) has been identified in humans and its expression is regulated during development and tissue remodeling. TIMP-1 overexpression in a mouse model of atherosclerosis showed a lesion reduction. The aim of the present study was to determine the serum levels of VEGF-A and TIMP-1 and to investigate their potential correlation with hypertension (HT), atherosclerotic markers and albuminuria in early stages of CKD and primary chronic glomerulonephritis (CGN). Design and method: CKD patients of stages 1 and 2 with CGN (n = 50) were included. As controls, there were healthy individuals (n = 40). Clearance of creatinine (Clcr) and albumin excretion were examined in the 24 h urine. VEGF-A and TIMP-1 levels were measured by an ELISA method. Intima media thickness (IMT) of carotid and femoral arteries and atheromatic plaque were evaluated by a high resolution ultrasonography. Results: There was a statistically significant difference between VEGF-A (200 ± 30, p < 0.0001), TIMP-1 (400 ± 20, p < 0.0001), HT (20 ± 5, p < 0.0001) and IMT (0.3 ± 0.09, p < 0.0001) in the patient group. There was a statistically significant negative strong correlation between levels of VEGF-A and TIMP-1 (r = -0.7, p < 0.0001), such as between TIMP-1 and IMT (r = -0.65, p < 0.0001). There was a statistically positive correlation between VEGF-A and IMT (r = 0.6, p < 0.0001). Further, VEGF-A and TIMP-1 levels were independently correlated with HT, IMT and atheromatic plaque. Conclusions: Our study suggests that serum levels of VEGF-A and TIMP-1 might present independent risk factors of hypertension, atherosclerosis and albuminuria, at least in the early stages of primary glomerulonephritis to the progression of CKD.