Systemic Inflammation and the Risks of Adverse Kidney Outcomes in Adults With Atherosclerotic Cardiovascular Disease.

Abstract

Rationale & objective: Inflammasome activation is involved in the pathogenesis of both atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD). This study investigated whether systemic inflammation, measured by C-reactive protein (CRP), is associated with adverse kidney outcomes in adults with ASCVD.

Study design: Retrospective cohort study.

Setting & participants: 83,928 adults with ASCVD in Stockholm, Sweden, who underwent routine CRP testing between 2007 and 2021.

Exposure(s): CRP was defined as the geometric mean of serum CRP levels within a 3-month ascertainment window, excluding CRP values potentially associated with an acute inflammatory process.

Outcome(s): AKI (based on diagnosis code or KDIGO serum creatinine criteria) and a composite kidney outcome defined as sustained >30% decline in eGFR or kidney failure.

Analytical approach: Cause-specific Cox proportional hazards regression.

Results: 54% of the cohort was male, with mean age of 71 years. 59% of participants had systemic inflammation (CRP ≥2 mg/L). Over a median follow-up of 6.4 years (interquartile range, 3.1-9.8 years), 8371 kidney events, 10,757 AKI events, and 24,954 deaths were recorded. Compared with CRP <1 mg/L, higher CRP categories were associated with increased risks of both outcomes. Compared to a CRP of 1 or less, the adjusted HRs for the composite kidney outcome were 1.16 (95% CI, 1.09-1.23) for CRP >1-3 mg/L, 1.24 (1.17-1.32) for CRP >3-10 mg/L, and 1.35 (1.25-1.46) for CRP >10-20 mg/L. For AKI, the HRs were 1.18 (1.12-1.25), 1.34 (1.27-1.42), and 1.37 (1.28-1.47), respectively.

Limitations: Unmeasured confounding inherent to observational studies.

Conclusions: In this large cohort of adults with ASCVD, elevated CRP levels were associated with higher risks of adverse kidney outcomes.