Low-grade inflammation and cardiovascular events among patients with chronic kidney disease

Chronic inflammation is associated with cardiovascular disease in the general population, but data on patients with chronic kidney disease (CKD) are limited. We sought to assess whether systemic low-grade inflammation is independently associated with cardiovascular events in CKD patients not yet on kidney replacement therapy, with or without a history of atherosclerotic cardiovascular disease (ASCVD).

CKD-REIN is a prospective cohort study of adults with CKD stages 2-5, conducted in 40 French nephrology outpatient facilities. Baseline high-sensitivity plasma C-reactive protein (hs-CRP) was centrally measured using an immunoturbidimetric method. Systemic low-grade inflammation was defined as hs-CRP ≥2 mg/L. Cox proportional hazards models estimated cause-specific hazard ratios (HR) and 95% confidence intervals (CI) for major adverse cardiovascular events (MACE; composite of stroke, myocardial infarction, or cardiovascular death) or hospitalization for heart failure (HHF).

We included 2078 patients: 67% men, mean (SD) age 67(13) years, mean eGFR 36(12) mL/min/1.73 m2, 38% with history of ASCVD, median hs-CRP concentration 2.4 mg/L (inter-quartile range 1.1-5.1). After median follow-up of 5 years, 171 patients had a MACE and 207 had HHF. After controlling for potential confounders, a twofold increase in hs-CRP was associated with a 12% (95% CI 0-26) higher cause-specific hazard of MACE and a 26% (95% CI 13-40) higher cause-specific hazard of HHF.

In CKD patients not yet on kidney replacement therapy, systemic low-grade inflammation, measured through hs-CRP, is associated with occurrence of cardiovascular events independently of traditional risk factors, including a history of ASCVD.