Inflammatory and Cardiovascular Events in CKD: The Multi-Ethnic Study of Atherosclerosis.

Abstract

RATIONALE & OBJECTIVE Chronic kidney disease (CKD) is associated with a proinflammatory state caused by maladaptive immune response, predisposing to cardiovascular (CVD) and inflammatory/infectious disease outcomes. We sought to examine the association of chronic inflammation-related disease (ChrIRD) as compared to CVD events with worsening kidney function. STUDY DESIGN Longitudinal, observational study over 19 years follow-up. SETTING & PARTICIPANTS Participants free of CVD were enrolled from the Multi-Ethnic Study of Atherosclerosis (MESA), a multicenter, population-based cohort. EXPOSURE 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 UACR (urine albumin-creatinine ratio, mg/g). OUTCOME(S) 3 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 ICD (except kidney codes). ANALYTICAL APPROACH Proportional hazards regression analysis RESULTS: 6,705 participants (mean age 62 years, 53% female, 38.5% White, 27.6% Black, 22% Hispanic, 11.9% Chinese) were studied. Among study participants, 70% had no CKD, 17% low-risk CKD (eGFR>60 + UACR<10-29); 7% moderate-risk CKD (eGFR ≥60 + UACR 30-299), 4.6% high-risk CKD (eGFR 30-59 + UACR <30 or eGFR 45-59 + UACR 30-299 or eGFR ≥60 and UACR ≥300), 0.8% very high-risk (more advanced combinations of eGFR/UACR). Over 19-years follow-up, unadjusted incidence density (events/1000-person-years) of ChrIRD, CVD events were (respectively): 18, 11.9 for no CKD, 26.3, 18.4 low-risk, 39.7, 29.6 moderate-risk, 60.1, 35.4 high-risk CKD and 128.7, 56.6 very high-risk categories. After demographic adjustment, respective HRs (95% CI) for ChrIRD and CVD events were 1.23 (1.10-1.39), 1.35 (1.17-1.55) for low-risk, generally increasing to 3.87 (2.75-5.44), 2.84 (1.85-4.36) for very high-risk CKD categories. LIMITATIONS Unmeasured confounders and selection bias. CONCLUSIONS ChrIRD increased in a graded fashion with worsening CKD risk categories, starting with UACR > 10 mg/g.