Use of Measures of Inflammation and Kidney Function for Prediction of Atherosclerotic Vascular Disease Events and Death in Patients With CKD: Findings From the CRIC Study

Abstract

Traditional risk estimates for atherosclerotic vascular disease (ASVD) and death may not perform optimally in the setting of CKD. We sought to determine whether the addition of measures of inflammation and kidney function to traditional estimation tools improves prediction of these events in a diverse cohort of patients with CKD. Observational cohort study 2399 Chronic Renal Insufficiency Cohort (CRIC) study participants without history of cardiovascular disease at study entry. Baseline plasma levels of biomarkers of inflammation (interleukin (IL)-1β, IL-1RA (IL-1 receptor antagonist), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor β (TGFβ), high sensitivity C-Reactive protein (hs-CRP), fibrinogen, and serum albumin), measures of kidney function (estimated glomerular filtration rate (eGFR) and albuminuria), and the Pooled Cohort Equation Probability (PCEP) estimate. Composite of ASVD events (incident myocardial infarction (MI), peripheral arterial disease (PAD), and stroke) and death. Cox proportional hazard models adjusted for PCEP estimates, albuminuria, and eGFR. During a median follow-up of 7.3 years, 86, 61, 48, and 323 participants experienced MI, PAD, stroke, or death, respectively. 1-decile greater levels of IL-6 (adjusted Hazard Ratio [aHR], 1.12; 95% CI, 1.08-1.16; p<0.001), TNF-α (aHR, 1.09; 95% CI, 1.05-1.13; p<0.001), fibrinogen (aHR, 1.07; 95% CI, 1.03-1.11; p<0.001), and serum albumin (aHR, 0.96; 95% CI, 0.93-0.99; p<0.002) were independently associated with the composite ASVD-death outcome. A composite inflammation score (CIS) incorporating these four biomarkers was associated with a graded increase in risk for the composite outcome. The incidence of ASVD-death increased across the quintiles of risk derived from PCEP, kidney function, and CIS. The addition of eGFR, albuminuria, and CIS to PCEP improved (p=0.003) the area under the receiver operating characteristic curve for the composite outcome from 0.68 (95% CI, 0.66-0.71) to 0.73 (95% CI, 0.71-0.76). Data on cardiovascular death were not available. Biomarkers of inflammation and measures of kidney function are independently associated with incident ASVD events and death in CKD patients. Traditional cardiovascular risk estimates could be improved by adding markers of inflammation and measures of kidney function.