Biomarkers of Cardiovascular Disease and Mortality Risk in Patients with Advanced CKD

Abstract

Background and objectives The high risk of cardiovascular disease (CVD) and premature death in patients with CKD associates with a plethora of elevated circulating biomarkers that may reflect distinct signaling pathways or simply, are epiphenomena of CKD. We compared the predictive strength of 12 biomarkers analyzed concomitantly in patients with stage 5 CKD.Design, setting, participants, & measurements From 1994 to 2014, 543 patients with stage 5 CKD (median age =56 years old; 63% men; 199 patients had CVD) took part in our study on malnutrition, inflammation, and CVD in incident dialysis patients. Circulating levels of albumin, ferritin, high-sensitivity C-reactive protein (hsCRP), IGF-1, IL-6, orosomucoid, troponin T (TnT), TNF, soluble intracellular adhesion molecule, soluble vascular cellular adhesion molecule 1 (sVCAM-1), and platelet and white blood cell (WBC) counts were analyzed as predictors of the presence of clinically overt CVD at baseline, protein-energy wasting (PEW), and subsequent all-cause mortality. During follow-up for a median of 28 months, there were 149 deaths, 81 of which were caused by CVD.Results Most biomarkers were elevated compared with reference values and--except for albumin, ferritin, and IGF-1-higher in patients with CVD. In receiver operating characteristic analysis, age, IL-6, TnT, hsCRP, and IGF-1 were classifiers of baseline CVD and predictors of all-cause mortality. In addition to age, diabetes mellitus, smoking (for CVD), and PEW, only IL-6, relative risk (RR) 1.10 and 95% confidence interval ([95% CI], 1.02 to 1.19), sVCAM-1 RR 1.09 (95% CI, 1.01 to 1.17), and serum albumin RR 0.89 (95% CI, 0.83 to 0.95) associated with baseline CVD, and only WBC, hazard ratio (HR) 1.94 (95% CI, 1.34 to 2.82), IL-6 HR 1.79 (95% CI, 1.20 to 2.67), and TNF HR 0.65 (95% CI, 0.44 to 0.97) predicted all-cause mortality.Conclusions In addition to age and comorbidities, only IL-6, sVCAM-1, and albumin could-independently of other biomarkers-classify clinical CVD, and only IL-6, WBC, and TNF could-independently of other biomarkers-predict all-cause mortality risk. These data underscore the robustness of IL-6 as a classifier of clinically overt CVD and predictor of all-cause mortality in patients with stage 5 CKD.

IL‐10‐specific autoantibodies predict major adverse cardiovascular events in kidney transplanted patients ‐ a retrospective cohort study

“…In accordance with our data, persistent systemic inflammation is associated with all‐cause mortality in populations without kidney disease , and CRP is associated with death from coronary heart disease and ischemic stroke as well as nonvascular mortality in a large meta‐analysis . In regard to patients with advanced kidney disease, persistent inflammation is common and is associated with CVD and high mortality risk . We found no association between systemic inflammation or c‐aAbs before transplantation and the rate of graft loss although systemic inflammation was associated with delayed graft function.…”

Interaction of Soluble CXC Ligand 16 and Cardiac Injury Markers in Hemodialysis Patients

“…However, chronic inflammation is a complex pathological process that involves multiple pathways and numerous inflammatory factors. CRP is not a potent predictor of cardiovascular risk when compared with other cytokines [30]. In terms of our results, the tighter correlations of CXCL16 with cardiac injury markers suggest that the effect of CXCL16 and its associated inflammatory pathway on cardiomyocytes is possibly more direct and potent than that of CRP.…”

The Cardiovascular Burden in End-Stage Renal Disease

“…In several studies, it has been shown that IL-6 plasma levels were strong predictors of CV mortality in patients in pre-dialysis and dialysis stages, and it was more accurate than the albumin, PCR or TNF-α levels [25] . Guanidine compounds are able to induce the …”