Inflammatory and Cardiovascular Events in CKD: The Multi-Ethnic Study of Atherosclerosis (MESA)

Chronic kidney disease (CKD) is associated with a proinflammatory state caused by maladaptive immune response, predisposing individuals to cardiovascular (CVD) and inflammatory/infectious disease outcomes. We sought to examine the association of chronic inflammation-related disease (ChrIRD) as compared with CVD events with worsening kidney function.

Longitudinal, observational study over 19 years of follow-up.

Participants free of CVD were enrolled from the Multi-Ethnic Study of Atherosclerosis (MESA), a multicenter, population-based cohort.

Baseline 5-level CKD categories based on modified KDIGO (Kidney Disease Improving Global Outcomes) groups using estimated glomerular filtration rate (eGFR, mL/min/1.73m²) and urinary albumin-creatinine ratio (UACR, mg/g).

Three outcomes of interest: time to occurrence of first ChrIRD, time to first CVD, and time to all-cause mortality. ChrIRD encompassed inflammatory or infectious conditions identified using International Classification of Diseases codes (except kidney codes).

Proportional hazards regression analysis.

The study included 6,705 participants (mean age 62 years, 53% female, 38.5% White, 27.6% Black, 22% Hispanic, 11.9% Chinese). Among the study participants, 70% had no CKD, 17% had low-risk CKD (eGFR >60+UACR10-29); 7% had moderate-risk CKD (eGFR≥60+UACR 30-299), 4.6% had high-risk CKD (eGFR 30-59+UACR<30 or eGFR 45-59+UACR 30-299 or eGFR≥60 and UACR≥300), and 0.8% had very high-risk CKD (more advanced combinations of eGFR/UACR). Over 19 years of follow-up, the unadjusted incidence density (events/1,000-person-years) of ChrIRD and CVD events, respectively, was 18 and 11.9 for no CKD, 26.3 and 18.4 for low-risk CKD, 39.7 and 29.6 for moderate-risk CKD, 60.1 and 35.4 for high-risk CKD, and 128.7 and 56.6 for very high-risk CKD. After demographic adjustment, the respective hazard ratios for ChrIRD and CVD events were 1.23 (95% CI, 1.10-1.39) and 1.35 (95% CI, 1.17-1.55) for low-risk CKD, generally increasing to 3.87 (95% CI, 2.75-5.44) and 2.84 (95% CI, 1.85-4.36) for very high-risk CKD categories.

Unmeasured confounders and selection bias.

ChrIRD increased in a graded fashion with worsening CKD risk categories, starting with UACR >10mg/g.

In this observational study, we used a large community-based sample from the Multi-Ethnic Study of Atherosclerosis to evaluate the likelihood of, and risks associated with, inflammatory conditions with worsening kidney function. We studied a novel diagnostic entity called chronic inflammation-related disease (ChrIRD) encompassing several infectious and noninfectious inflammatory conditions. Over 19 years of follow-up, we demonstrated progressively higher risk of ChrIRD with worsening kidney function. The risks of ChrIRD are apparent in individuals with low levels of proteinuria and exceed cardiovascular disease at most stages of kidney function. This study highlights the importance of recognizing both infectious and noninfectious inflammatory conditions with worsening kidney function. Future studies should focus on ways to further understand this association and mitigate the risks.