Cardiovascular disease is the major cause of premature death in patients with chronic kidney disease (CKD).^1,2 Large prospective cohort studies have documented significant associations of worse kidney function and proteinuria with cardiovascular disease and mortality that are independent of traditional risk factors.^2-4 Coronary artery calcification (CAC) is highly prevalent and more severe in patients with CKD compared with those without CKD.^5-7 Coronary artery calcification independently predicts the risk of coronary heart disease and total cardiovascular disease more than traditional risk factors in the general population.^8,9

We studied the association of inflammatory biomarkers including C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) with chronic kidney disease (CKD). We conducted a case–control study among 201 CKD patients and 201 community-based controls in the greater New Orleans area. CKD was defined as estimated-glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or albuminuria ≥30 mg/24-h. Serum CRP, TNF-α, and IL-6 were measured using standard methods. Multivariable regression models were used to examine associations between the inflammatory biomarkers and CKD adjusting for important CKD risk factors, history of cardiovascular disease, and use of antihypertensive, antidiabetic, and lipid-lowering agents and aspirin. The multivariable-adjusted medians (interquartile-range) were 2.91 (1.47, 5.24) mg/L in patients with CKD vs. 1.91 (0.99, 3.79) mg/L in controls without CKD (p = 0.39 for group difference) for CRP; 1.86 (1.51, 2.63) pg/mL vs. 1.26 (1.01, 1.98) pg/mL (p < 0.0001) for TNF-α; and 2.53 (1.49, 4.42) pg/mL vs. 1.39 (0.95, 2.15) pg/mL (p = 0.04) for IL-6, respectively. Compared to the lowest tertile, the highest tertile of TNF-α (OR 7.1, 95 % CI 3.2 to 15.5) and IL-6 (OR 2.5, 95 % CI 1.1 to 5.5) were significantly associated with higher odds of CKD in multivariable-adjusted models. Additionally, higher TNF-α and IL-6 were independently and significantly associated with lower eGFR and higher albuminuria. Our data suggest that TNF-α and IL-6, but not CRP, are associated with the prevalence and severity of CKD, independent from established CKD risk factors, history of cardiovascular disease, and use of antihypertensive, antidiabetic, and lipid-lowering agents and aspirin.

Background. The metabolic syndrome is a common risk factor for cardiovascular and chronic kidney disease (CKD) in Western populations. We examined the relationship between the metabolic syndrome and risk of CKD in Chinese adults. Methods. A cross-sectional survey was conducted in a nationally representative sample of 15 160 Chinese adults aged 35–74 years. The metabolic syndrome was defined as the presence of three or more of the following risk factors: elevated blood pressure, low high density lipoprotein (HDL)-cholesterol, high triglycerides, elevated plasma glucose and abdominal obesity. CKD was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m ² and elevated serum creatinine was defined as ≥1.14 mg/dl in men and ≥0.97 mg/dl in women (≥95th percentile of serum creatinine in Chinese men and women aged 35–44 years without hypertension or diabetes, respectively). Results. The multivariate-adjusted odds ratios [95% confidence interval (CI)] of CKD and elevated serum creatinine in participants with compared to those without the metabolic syndrome were 1.64 (1.16, 2.32) and 1.36 (1.07, 1.73), respectively. Compared to participants without any components of the metabolic syndrome, the multivariate-adjusted odds ratios (95% CI) of CKD were 1.51 (1.02, 2.23), 1.50 (0.97, 2.32), 2.13 (1.30, 3.50) and 2.72 (1.50, 4.93) for those with 1, 2, 3, and 4 or 5 components, respectively. The corresponding multivariate-adjusted odds ratios (95% CI) of elevated serum creatinine were 1.11 (0.88, 1.40), 1.39 (1.07, 2.04), 1.47 (1.06, 2.04) and 2.00 (1.32, 3.03), respectively. Conclusions. These findings suggest that the metabolic syndrome might be an important risk factor for CKD in Chinese adults.

Clinical and epidemiological data indicate that inflammation may be associated with insulin resistance. We examined the association between inflammatory markers, such as ferritin, uric acid, white cell counts, fibrinogen, and C-reactive protein, and insulin resistance among 5,959 adults, aged ≥20 years and without diabetes (fasting glucose <126 mg/dl and not taking diabetes medication), who participated in the Third National Health and Nutrition Examination Survey. Insulin resistance was calculated using the homeostasis model assessment (HOMA). Levels of ferritin, uric acid, white cell counts, fibrinogen, and C-reactive protein were significantly higher in individuals with a higher HOMA of insulin resistance (HOMA-IR). After adjustment for age, sex, race, education, physical inactivity, current and former smoking, alcohol intake, use of nonsteroidal anti-inflammatory drugs, systolic blood pressure, BMI, waist circumference, serum total cholesterol, and triglycerides, a 1-SD higher ferritin (126.1 ng/ml), uric acid (1.4 mg/dl), white blood cell count (2.2 × 10⁹/l), and fibrinogen (80.6 mg/dl) was associated with a 0.10 (95% CI 0.03–0.17, P = 0.004), 0.16 (0.08–0.24, P < 0.001), 0.16 (0.09–0.22, P < 0.001), and 0.12 (0.05–0.18, P = 0.001) higher HOMA-IR, respectively. Clinically elevated C-reactive protein (≥1.0 mg/dl) was associated with a 0.63 (0.23–1.04, P = 0.003) higher HOMA-IR. These findings indicate that elevated levels of inflammatory markers are positively and independently associated with insulin resistance. Further studies should examine the potential causal effect of inflammation on insulin resistance.