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 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): Acute kidney injury (AKI; based on diagnosis code or Kidney Disease: Improving Global Outcomes [KDIGO] serum creatinine criteria) and a composite kidney outcome defined as a sustained>30% decrease in estimated glomerular filtration rate or kidney failure.

Analytical approach: Cause-specific Cox proportional hazards regression.

Results: 54% of the cohort was male, with a mean age of 71 years, and 59% of participants had systemic inflammation (CRP≥2mg/L). During a median follow-up of 6.4 years (IQR, 3.1-9.8 years), 8,371 kidney events, 10,757 AKI events, and 24,954 deaths were recorded. Compared with CRP<1mg/L, higher CRP categories were associated with increased risks of both outcomes. Compared with a CRP of≤1mg/L, the adjusted HRs for the composite kidney outcome were 1.16 (95% CI, 1.09-1.23) for CRP>1-3mg/L, 1.24 (1.17-1.32) for CRP>3-10mg/L, and 1.35 (1.25-1.46) for CRP>10-20mg/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, increased CRP levels were associated with higher risks of adverse kidney outcomes.

Plain-language summary: Inconsistent evidence exists regarding the association between the circulating blood marker of inflammation C-reactive protein (CRP) and kidney outcomes. We conducted an observational study in more than 83,000 adults with atherosclerotic cardiovascular disease undergoing routine care. The study showed that CRP levels were higher in participants with lower levels of kidney function and that CRP was associated with more rapid declines in kidney function over time as well as a greater risk of acute kidney injury.

Keywords: Atherosclerosis; C-reactive protein; SCREAM; chronic kidney disease; inflammation; myocardial infarction; stroke.