Serum Matrix Metalloproteinases MMP-2 and MMP-3 Levels in Dialysis Patients Vary Independently of CRP and IL-6 Levels

Abstract

Background: Patients on chronic hemodialysis or peritoneal dialysis often develop an inflammatory state that causes morbidity and mortality. Cross-sectional studies of dialysis patients have determined that C-reactive protein (CRP) is a predictor of morbidity. Little is known as to whether CRP, cytokines, such as IL-6 and IL-1β that stimulate the synthesis of CRP, or matrix metalloproteinases (MMPs) are markers of inflammation in patients on dialysis. Methods: We assayed by ELISA serum levels of MMP-2, MMP-3, IL-6 and CRP in healthy individuals and in patients with pre-end-stage renal disease (pESRD, n = 10), peritoneal dialysis (PD, n = 11), hemodialysis (HD, n = 17) and renal transplant (TX, n = 10). Results: MMP-2 was significantly elevated before dialysis, perhaps indicative of progressive chronic renal sclerosis. MMP-3 was markedly elevated in hemodialysis patients but not in pESRD or PD patients, and may be related to the hemodialysis process and/or accelerated atherogenesis in these patients. IL-6 was significantly elevated in all patient groups, including pESRD patients. There were no statistically significant differences in CRP levels among the study groups. CRP correlated with IL-6, but not with MMP-2 or MMP-3. Conclusions: The data indicate that there are measurable differences in the expression of MMPs within the dialysis patient population. Because dialysis can be associated with local and systemic inflammation, increased levels of MMP-3 in the hemodialyis group may be a reflection of gene stimulation induced by inflammatory cytokines and should be considered as a marker of chronic, local inflammation.