Matrix metalloproteinase-1 and-2 as markers of mineral bone disease in chronic kidney disease patients

Background: In the past few years, a distinct and multifactorial clinical entity called chronic kidney disease-mineral and bone disorder (CKD-MBD) that leads to decreased bone density and osteoporosis has been identified. The aim of this study was to assess the levels of the matrix metalloproteinase-1 and -2 (MMP-1 and MMP-2) in chronic kidney disease (CKD) patients of various disease stages in correlation to other bone turnover markers (BTM). This study is an initial investigative approach to a possible role of matrix metalloproteinases (MMPs) in the evaluation of bone disease in uremic patients. Methods: We enrolled 60 patients at different stages of pre-dialysis CKD, 20 patients on hemodialysis (HD), and 20 age-matched healthy controls. Serum intact parathyroid hormone (iPTH), osteocalcin (OC), N-terminal propeptide of type I collagen (P1NP), and beta-C-terminal telopeptide of type I collagen (beta-CTX), were measured by electrochemiluminescence on automatic analyzers. Serum MMP-1 and MMP-2 levels were estimated using a commercial enzyme-linked immunosorbent assay (ELISA). Serum levels of urea, creatinine, calcium, phosphorus, and alkaline phosphatase were estimated. Creatinine clearance (ClCr) was calculated using the traditional clearance formula based on a 24-hour urine collection. Results: Serum iPTH, OC, P1NP, beta-CTX concentrations were significantly higher (p < 0.0001) while ClCr was significantly lower (p < 0.0001) in CKD patients, as compared with those of healthy controls. A positive correlation was established between serum MMP-1 and OC levels (r = 0.245, p = 0.014), as well as with serum beta-CTX levels (r = 0.197, p = 0.048), and a negative correlation between MMP-2 and OC (r = -0.222, p = 0.025). Conclusions: In CKD patients MMP-1 serum levels may reflect increased bone turnover rates.