Serum metalloproteinases MMP-2, MMP-9 and metalloproteinase tissue inhibitors TIMP-1 and TIMP-2 in patients on hemodialysis

Abstract

Background: We assessed the effect of hemodialysis (HD) and chronic kidney disease (CKD) on the serum levels of metalloproteinase-2 (MMP-2), MMP-9 and metalloproteinase tissue inhibitors (TIMP-1) and TIMP-2.

Methods: 18 patients on regular HD treatment with low-flux, cuprophane membrane, 15 non-dialyzed patients with CKD and 15 healthy controls were sampled. The serum MMP and TIMP concentrations were determined by ELISA assays.

Results: MMP-9, TIMP-1, and TIMP-2 serum levels were significantly decreased in HD patients to 32.7 ± 20.1 ng/ml, 178.8 ± 73.0 ng/ml, and 103.4 ± 55.3 ng/ml compared with 482.3 ± 139.5, 367.6 ± 75.5 ng/ml, and 299.7 ± 63.2 ng/ml in patients with CKD and 594.6 ± 154.7 ng/ml, 354.5 ± 81.2 ng/ml, and 272.4 ± 91.8 ng/ml in healthy controls, respectively, (P < 0.001 vs. HD patients). MMP-2 was lower in patients with CKD: 405.6 ± 106.1 ng/ml compared with 516.9 ± 81.7 ng/ml in controls (P = 0.02). The MMP-2/TIMP-2 ratio was increased in HD patients compared with both patients with CKD and controls. In the course of an HD session, MMP-2 and TIMP-1 serum levels were significantly decreased from pre-HD 570.0 ± 256.5 and 178.8 ± 66.9 ng/ml to post-HD 492.6 ± 212.5 and 144.6 ± 44.2 ng/ml (P = 0.004 and 0.013, respectively). However, the MMP-9/TIMP-1 ratio increased from pre-HD 0.15 (2.19) (median, range) to 0.23 (0.33) after a HD session (P = 0.03). CRP was positively correlated with MMP-9 and MMP-9/TIMP-1 ratio in HD patients and patients with CKD (r = 0.67; P = 0.03).

Conclusions: The MMP-9/TIMP-1 ratio increased during HD sessions, although their absolute levels were lowered. This change may represent a chronic state of enhanced fibrosis in patients undergoing HD.