High circulating levels of large splice variants of tenascin-C is associated with mortality and cardiovascular disease in chronic kidney disease patients

Abstract

Objectives: Tenascin-C (TN-C) is an adhesion-modulating extracellular matrix glycoprotein which is overexpressed in various organs under disease conditions (infection and inflammation). In patients with heart disease, plasma TN-C levels have been shown to be predictive of cardiac remodeling. Chronic kidney disease (CKD) is associated with a state of chronic inflammation and high cardiovascular morbidity and mortality.

Methods: In a prospective observational study, we examined the relationship between plasma concentration of large splice variants of TN-C (cTN-C) and cardiovascular outcomes, we studied a cohort of 94 prevalent CKD patients (mean±SD age: 68±13; 31% at CKD stages 2-3, 31% at stages 4-5, 38% at stage 5D).

Results: Plasma cTN-C levels were elevated in this population and tended to rise as CKD progressed, with the increase becoming statistically significant at CKD stage 4-5 and 5D. Multivariate linear regression analysis indicated that CKD stage (p=0.04), IL-6 (p=0.02) and albumin (p=0.02) were independently associated with plasma cTN-C levels. During follow-up (mean duration: 969±405 days), 32 patients died (19 from CV events, 7 from infectious diseases and 6 from other causes). In a crude analysis, higher plasma cTN-C levels predicted overall and CV mortality (p=0.007 and p=0.003, respectively) and were associated with higher occurrence of CV events. Cox analyses confirmed that elevated plasma cTN-C levels were independently associated with cardiovascular events, cardiovascular and overall mortality.

Conclusion: Our findings suggest, for the first time, that plasma cTN-C levels are independently associated with cardiovascular outcomes in CKD patients. Further studies are needed in order to confirm the above observations and better understand TN-C's role in cardiovascular remodeling in CKD.