INCREASED CIRCULATING SERUM LEVELS OF MMP-9 AND VEGF-A ARE ASSOCIATED WITH OXIDATIVE

STRESS IN PATIENTS WITH PRIMARY GLOMERULONEPHRITIS AND EARLY STAGES OF

CHRONIC KIDNEY DISEASE

Grigorios G. Dimas1, Thomas J. Tegos2, Sofia G. Spiroglou3, Ilias E. Kanellos1, Ioannis M.Karamouzis3, Christos G Savopoulos1, Apostolos I Hatzitolios1, Dimitrios M. Grekas1.

 1 1st Propaedeutic Medical Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Greece2 1st Neurology Medical Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Greece3 Biochemistry Laboratory, AHEPA University Hospital, Aristotle University of Thessaloniki, Greece

Background

• Increased oxidative stress (OS) in chronic kidney disease (CKD) was suggested to be both a cause and an effect of renal injury.

• The concentration of 15-F2t-isoprostane (15-F2t-IsoP) in serum has been considered as a reliable biochemical index of OS in patients with several pathological conditions including primary chronic glomerulonephritis (CGN) and CKD.

• Matrix metalloproteinase-9 (MMP-9) is considered to be the main enzyme that degrades collagen type-IV (col-IV) and has been implicated in CKD and cardiovascular disease (CVD).

• It remains controversial the mechanism by which vascular endothelial growth factor (VEGF) works in the kidney, as well as in the vessels at least in the early stages of CKD.

Aim

• The aim of this study was to investigate the serum levels of MMP-9 and VEGF-A and

their potential correlation with 15-F2t-IsoP in early stages of CKD and CGN.

Methods

• CKD patients of stages 1 and 2 with CGN (n=40) were included. As controls, there were

healthy individuals (n=40). MMP-9, VEGF-A and 15-F2t-IsoP levels were determined by

ELISA.

Results

• The levels of MMP-9 were significantly higher in patients than in the control groups

(500±50, p<0.0001), such as VEGF-A (250±20, p<0.0001) and 15-F2t-IsoP (80±15,

p<0.0001).

• There was a positive strong correlation between MMP-9 and VEGF-A (r= 0.7, p<0.0001),

MMP-9 and 15-F2t-IsoP (r= 0.75, p<0.0001) and VEGF-A and 15-F2t-IsoP (r= 0.6,

p<0.0001).

• Further, MMP-9 and VEGF-A levels were independent correlates of OS.

Conclusion

• This study suggests that MMP-9 and VEGF-A might present independent correlates of

oxidative stress in early stages of CKD.