1. SERUM LEVELS OF TISSUE INHIBITOR OF METALLOPROTEINASE-2 AND OX-LDL ARE ASSOCIATED WITH ATHEROSCLEROSIS IN PATIENTS WITH CΗRONIC KIDNEY DISEASE Grigorios G. Dimas 1, Thomas J. Tegos 2, Sofia G. Spiroglou 3, Ioannis M. Karamouzis 3, Ilias E. Kanellos 1, Christos G. Savopoulos 1, Apostolos I. Hatzitolios 1, Dimitrios M. Grekas 1. 1 1st Propaedeutic Medical Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Greece 2 1st Neurology Medical Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Greece 3 Biochemistry Laboratory, AHEPA University Hospital, Aristotle University of Thessaloniki, Greece

2. Background Conflicting studies cannot establish at present a clear role for tissue inhibitor of metalloproteinase-2 (TIMP-2) in the pathogenesis of diabetic albuminuria and atherosclerosis. The evolution of oxidant stress from early stages of renal function decline is not fully clear. The concentration of oxidized-LDL (ox-LDL) in serum has been considered as a reliable biochemical index of oxidative stress in patients with several pathological conditions including chronic kidney disease (CKD).

3. Aim The aim of the present study was to investigate the serum levels of TIMP-2 and ox- LDL and their potential role in atherosclerosis and albuminuria in patients with CKD.

4. Methods CKD patients of stages 1 and 2 (n=50) were included. As controls, there were healthy individuals (n=40). TIMP-2 and ox-LDL levels were measured by an ELISA method. Intima media thickness (IMT) of carotid and femoral arteries and atherosclerotic plaque were determined by a high resolution ultrasonography.

5. Results There was a statistically significant difference between ox-LDL (50±5, p<0.0001), TIMP-2 (100±5, p<0.0001) and IMT (0.3±0.1, p<0.0001) in the patient group. There was a statistically significant negative strong correlation between levels of ox-LDL and TIMP-2 (r= -0.7, p<0.0001), such as between TIMP-2 and IMT (r= -0.7, p<0.0001). There was a statistically positive correlation between ox-LDL and IMT (r= 0.7, p<0.0001). Further, ox-LDL and TIMP-1 levels were independently correlated with IMT and atheromatic plaque.

6. Conclusion This study suggests that serum levels of TIMP-2 and ox-LDL were found to be independent risk factors of atherosclerosis as well as of albuminuria in early stages of CKD.