Fibroblast Growth Factor 23 and Matrix-Metalloproteinases in Patients with Chronic Kidney Disease: Are They Associated with Cardiovascular Disease?

Abstract

Background: High cardiovascular risk in patients with chronic kidney disease (CKD) may be related to mineral disorder and microinflammation. Fibroblast growth factor 23 (FGF-23) is a phosphatonin and inhibitor of calcitriol synthesis, which is associated with poor prognosis in CKD patients starting dialysis. Matrix-metalloproteinases (MMP-2, MMP-9) contribute to myocardial remodeling and arterial calcification. FGF-23 and MMPs levels are altered in CKD, however, little is known about their association and relation to cardiovascular (CV) disease. Methods: Standard laboratory parameters, plasma levels of MMP-2, MMP-9, FGF-23, PAPP-A and CV disease history were assessed in 80 patients with CKD 1–5 and 44 healthy control subjects. Results: FGF-23 and MMP-2 (assessed by ELISA) were higher in CKD patients compared to controls. FGF-23 increased from CKD 3, whereas MMP-2 increased only in CKD 5. FGF-23 was positively associated with MMP-2, adjusted to age, eGFR, phosphatemia, calcitriol and parathormone. FGF-23 independently correlated with parathormone and inversely with calcitriol, whereas MMP-2 was related to phosphatemia. FGF-23 was higher in subjects with a history of CV disease compared to those free of such history (559.0 vs.184.0 RU/ml), adjusted to age and eGFR. Conclusion: Our data suggest a possible relationship between FGF-23, MMP-2 and CV disease in CKD. Potential causality of this association remains to be elucidated.

Matrix metalloproteinases (MMP-2,9) and their tissue inhibitors (TIMP-1,2) as novel markers of stress response and atherogenesis in children with chronic kidney disease (CKD) on conservative treatment

“…Serum MMP-2 concentrations in the examined population were elevated, when compared to controls, similar to the results obtained in adults by others (Peiskerova et al 2009; Chang et al 2006). The novelty of our observation was the fact that MMP-2 levels increased gradually with the progression of CKD and correlated with GFR.…”

“…Chang et al (2006) found decreased levels of gelatinase B, whereas Peiskerova et al (2009) noticed no difference between controls and CKD patients. In our group, a gradual increase was observed, together with an inverse correlation to GFR values.…”

Activation of Arterial Matrix Metalloproteinases Leads to Vascular Calcification in Chronic Kidney Disease

“…Chung et al [18] also found a positive correlation between patient serum phosphorus levels and MMP-2 expression in the inferior epigastric arteries. Similarly, in CKD patients there was a positive relationship of hyperphosphatemia with serum MMP-2 levels [20]. However, we found increased tissue expression early in the course of CKD when the animals were not yet hyperphosphatemic.…”

Changes in fibroblast growth factor 23 levels in normophosphatemic patients with chronic kidney disease stage 3 treated with lanthanum carbonate: results of the PREFECT study, a phase 2a, double blind, randomized, placebo-controlled trial

“…FGF23 levels are elevated early in CKD and increase as the disease progresses [2]. Increased circulating FGF23 levels are associated with an increased risk of peripheral vascular calcification [3], heart disease [4-9] and death [10-12]. In animal models, FGF23 can directly induce left ventricular hypertrophy, which can be prevented by blocking the intracellular signaling pathway stimulated by FGF23 [13].…”