Serum Metalloproteinases MMP-2, MMP-9, and Metalloproteinase Tissue Inhibitors (TIMP) in Patients Are Associated with Arteriovenous Fistula Maturation

Abstract

Objective: Many vascular surgeons construct arteriovenous fistula (AVF) for hemodialysis access as the primary choice access. However, a significant number of AVF fail to mature, leading to patient frustration and repeated operations. MMP activity, particularly MMP-2 and MMP-9, are considered important for AVF maturation. We therefore sought to identify whether serum MMPs could serve as a biomarker for predicting future successful AVF maturation. Methods: Blood was collected at the time of surgery from patients with chronic renal insufficiency requiring long-term access. Serum was separated from whole blood by the use of an ultracentrifuge at 1000g for 10 minutes. Serum aliquots were frozen at –80°C until used for analysis. MMP-2, MMP-9, TIMP-2, and TIMP-4 were assayed using the ELISA technique. Patients were divided into failed and matured groups, depending on clinical end points. Successful maturation was considered in patients who had at least three successful hemodialysis access episodes. MMP/TIMP ratios were calculated as an index of the MMP axis activity because MMP activity parallels alterations in their TIMPs. Results: Of the 20 patients who were enrolled, 13 had successful maturation, and 7 had failure of AVF maturation. Significantly higher serum levels of MMP-2/TIMP-2 were found in patients who had AVF that matured compared with those that failed (P = .003). Similarly, a trend toward increased serum levels of MMP-9/TIMP-4 was found in patients with successful AVF (P = .06; see Fig). Conclusions: These data show that serum MMPs and the associated inhibitors could potentially play a role as a biomarker for future AVF maturation.