Peripheral blood level alterations of MMP-2 and MMP-9 in patients with chronic kidney disease on conservative treatment and on hemodialysis
Introduction
Patients with chronic kidney disease (CKD) and on hemodialysis (HD) treatment are at significantly higher cardiovascular risk than the general population [1]. Even mild kidney dysfunction should be considered a medical condition predisposing to increased cardiovascular risk [2]. Atherosclerotic cardiovascular disease (CVD) is further accelerated by long-term HD treatment and appears to increase mortality and morbidity of these patients [3].
Matrix metalloproteinases (MMPs) are involved in the process of atherosclerosis. MMPs, such as MMP-2 and 9 degrade the type IV collagen, the major structural component of basement membrane. There has been an emphasis on these two MMPs because their elevated expression were demonstrated within plaques. They play a part in plaque rupture by weakening it [4]. In previous study, Chang et al. [5] suggested that increased MMP-2 and decreased MMP-9 levels contribute to the pathogenesis of CKD. More recent studies found that increased MMP-2 levels correlates with proteinuria, oxidative stress, CVD prevalence and the atherosclerosis marker — intima media thickness (IMT) both in CKD patients [6], [7] and in dialyzed population [8], [9]. In the case of MMP-9, its reduced levels were observed in CKD patients [5]. Moreover, Ebihara et al. [10] showed that chronic dialysis induced expression of the mRNA MMP-9 in peripheral blood monocytes, without significant elevation of serum MMP-9. In our previous studies [8], [9] we also did not observed the differences in the MMP-9 levels between the dialyzed patients and healthy controls and we could not find the correlation between this metalloproteinase and oxidative stress markers, CVD prevalence or atherosclerosis.
Inflammation in patients with end-stage renal disease is associated with malnutrition, cardiovascular morbidity and death [11]. Inflammatory stimuli leads to release of cytokines that are involved in many systemic changes, including increased synthesis and release of acute-phase proteins, such as C-reactive protein (CRP), and the suppression of other acute-phase proteins such as albumin [12]. MMP gene expression is regulated by inflammatory cytokines, and their excessive or inappropriate synthesis has been associated with the pathogenesis of many tissue destructive processes in uremia such as atherosclerotic CVD [4], [6], [7], [8], [9].
MMP-2 and MMP-9 are the important factors participating in progression of atherosclerosis in CKD and HD patients [6], [7], [8], [9]; however the results from data concerning their blood levels in these populations of patients are conflicting and incomplete. The purpose of the current study was to measure the serum MMP-2 and MMP-9 concentrations in CKD stages from 1 + 2 to 5, as well before and after the HD session, and also to identify potential factors that may affect their levels in these patients.
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Subjects
The study involved 58 adult patients with different stages of CKD and 23 patients on HD treatment; they were clinically stable and free of active infection and autoimmune diseases. None of the patients received immunosuppressive treatment, lipid-lowering agents, non-steroidal anti-inflammatory drugs or antioxidants such as vitamin E, C or allopurinol at the time of the study. Eighteen healthy subjects who were receiving no drugs or vitamin supplements at the time of the study volunteered as
Demographic data
Detailed characteristics of subjects are shown in Table 1. In patients with CKD from stage 3 we noted the decrease in erythrocyte count, hemoglobin concentration (both p < 0.01), iron levels (p < 0.05), whereas creatinine and leukocyte count were increased (both p < 0.05) compared to controls. We noted in patients with CKD from stage 3 the decrease in erythrocyte count, hemoglobin concentration (both p < 0.01), iron levels (p < 0.05), whereas creatinine and leukocyte count were increased (both p < 0.05).
Discussion
According to our knowledge, this is the first study that demonstrates the parallel alteration of the MMP-2 and MMP-9 serum concentrations in patients with different CKD stages, as well before and after the HD session. Moreover, we have tried to find the factors that affect these MMP levels in the studied groups of uremic patients.
In the present investigation, we did not observed the differences in the MMP-2 levels in different stages of CKD patients compared to the controls. Starting from stage
Acknowledgments
This work was supported by a grant no. 3-28568F provided by the Medical University in Bialystok.
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