Serum matrix metalloproteinase‐3 in hemodialysis patients with dialysis‐related amyloidosis

Abstract

Matrix metalloproteinase-3 (MMP-3) has been linked to osteoarticular destruction in rheumatic arthritis. To investigate the role of MMP-3 in dialysis-related amyloidosis (DRA), we determined serum MMP-3 in long-term hemodialysis (HD) patients with and without clinical manifestations of DRA. Thirty-three subjects (63% female, 3% diabetic) enrolled in the study between September 2001 and June 2003. All patients underwent standard HD three times per week, using high-flux dialyzers. Four patients had active DRA complications (DRA patients), whereas the others (n = 29) had no evidence of DRA. We determined serum concentrations of MMP-3, C-reactive protein (CRP), beta(2)-microglobulin (beta(2)M), and interleukin-6 (IL-6). We also studied the effects of hemodiafiltration (HDF) on inflammatory measures by transferring the DRA patients from regular HD to predilution HDF. The DRA group had been on dialysis significantly longer than the control group. Significant positive correlations were observed between MMP-3 and IL-6 (R(2) = 0.5143, p < 0.0001) and MMP-3 and CRP (R(2) = 0.6492, p < 0.0001). IL-6 levels increased after a single dialysis treatment, but this effect was minimal with predilution HDF (the increment of IL-6 levels did not exceed 10 pg/mL). Serum MMP-3 levels decreased in parallel with the decrease of IL-6. MMP-3 serum levels increase in accordance with clinical manifestations of DRA and elevated circulating levels of IL-6. For the evaluation of the pathophysiologic state of DRA, serum MMP-3 may be a useful predictor indicative of chronic inflammation and osteoarticular disorders in DRA patients.