Cardiovascular risk biomarkers in CKD: the inflammation link and the road less traveled

Abstract

End-stage renal disease patients suffer a syndrome of accelerated aging characterized by a 10- to 100-fold increase in cardiovascular and all-cause mortality when compared to age-matched controls. No specific therapeutic interventions have been shown to improve this dismal outcome. Inflammation, chronic kidney disease-mineral and bone disorder (CKD-MBD) and other biomarkers predict outcome in observational studies. However, we lack clinical trials that address the role of these biomarkers in risk stratification and therapeutic decision making. Biomarkers may also provide insights into the pathophysiology of disease and identify novel therapeutic targets. Inflammation emerges as a prime potential target for intervention. Thus, CKD-MBD biomarkers, asymmetrical dimethyl arginine and tri-iodothyronine have a link to inflammation. Interleukin-6 (IL-6) is one of the inflammation biomarkers with highest predictive value for outcome in ESRD. Biologicals targeting IL-6 are approved for the treatment of chronic inflammatory conditions such as rheumatoid arthritis. Furthermore, trials are underway to test IL-6 targeting potential to decrease cardiovascular injury in non-CKD patients. In this regard, targeting IL-1 was recently shown to decrease systemic inflammation in hemodialysis patients. The success of these trials will likely influence future studies on biomarker targeting in CKD.