Abstract
Objective: Matrix metalloproteinase-2 (MMP-2) is considered to be the main enzyme that degrades collagen type-IV (col-IV) and has been implicated in chronic kidney disease (CKD) and cardiovascular disease (CVD). Tissue inhibitor of metalloproteinase-2 (TIMP-2) participates in nephron morphogenesis and inhibits endothelial cell growth induced by fibroblast growth factor, as well MMP-2. Conflicting studies cannot establish at present a clear role for TIMP-2 in the pathogenesis of albuminuria and atherosclerosis. The aim of the present study was to investigate the serum levels of TIMP-2 and MMP-2 and their potential role in hypertension, atherosclerosis and albuminuria in patients with 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. Patients with active inflammatory disease or malignancy were excluded. As controls, there were healthy individuals (n = 40). Clearance of creatinine (Clcr) and albumin excretion were examined in the 24 h urine. TIMP-2 and MMP-2 levels were measured by an ELISA method. Blood pressure (BP) was taken using a manual sphygmomanometer. Intima media thickness (IMT) of carotid and femoral arteries and atherosclerotic plaque were determined by a high resolution ultrasonography. Results: There was a statistically significant difference between MMP-2 (250 ± 10, p < 0.0001), TIMP-2 (100 ± 20, p < 0.0001), BP (25 ± 15, p < 0.0001) and IMT (0.15 ± 0.2, p < 0.0001) in the patient group. There was a statistically significant negative strong correlation between levels of MMP-2 and TIMP-2 (r = -0.7, p < 0.0001), such as between TIMP-2 and IMT (r = -0.62, p < 0.0001). There was a statistically positive correlation between MMP-2 and IMT (r = 0.75, p < 0.0001). Further, MMP-2 and TIMP-1 levels were independently correlated with BP, IMT and atheromatic plaque. Conclusions: This study suggests that serum levels of TIMP-2 and MMP- 2 were found to be independent risk factors of hypertension, atherosclerosis as well as of albuminuria in early stages of CKD and CGN.
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