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

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 ≥2 mg/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 <1 mg/L, higher CRP categories were associated with increased risks of both outcomes. Compared with a CRP of ≤1 mg/L, 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, 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.