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

Abstract

ObjectivesTenascin-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. MethodsIn 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). ResultsPlasma 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. ConclusionOur 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.