Insulin Resistance, Inflammation, and Vascular Disease in Nondiabetic Predialysis Chronic Kidney Disease Patients

Background: Chronic kidney disease (CKD) is associated with high cardiovascular morbidity and mortality, which is not fully explained by traditional risk factors; hence, the interest in nontraditional risk factors such as inflammation and insulin resistance (IR). Though IR is shown in nondiabetic CKD, its association with vascular disease and inflammation in this population is unknown, and is what this study aims to investigate. Hypothesis: IR and inflammation are related to vascular disease in nondiabetic predialysis CKD patients. Methods: We studied carotid-artery intima-media thickness (IMT) and endothelial function (brachial artery flow mediated dilation [FMD]) in 35 nondiabetic predialysis patients with stage 3-5 CKD and 35 age-and gender-matched controls. Insulin resistance was measured using the homeostasis model assessment for insulin resistance score (HOMA-IR), inflammation by high-sensitivity CRP (hsCRP), and their relationship with FMD and IMT. Results: Patients with CKD showed reduced FMD (3.34 +/- 2.14% vs 5.27 +/- 1.78%, P < 0.001) and increased IMT (0.78 +/- 0.22 mm vs 0.64 +/- 0.16 mm, P = 0.003) compared with controls. The CKD patients had a higher HOMA-IR (2.20 +/- 1.08 vs 1.13 +/- 0.64, P < 0.001) and hsCRP (3.25 +/- 5.47 mg/L vs 1.10 +/- 1.85 mg/L [median +/- interquartile range], P = 0.02). In the study population, HOMA-IR was directly related to hsCRP. After adjusting for traditional risk factors, high HOMA-IR and hsCRP were significantly related to decreased FMD (adjusted beta = -0.44, 95% confidence interval [CI]:-1.55 to -0.08, P = 0.003 and adjusted beta = -0.51, 95% CI: -0.51 to -0.15, P = 0.001) and increased IMT (adjusted beta = 0.62, 95% CI: 0.54-1.90, P = 0.001 and adjusted beta = 0.43, 95% CI: 0.08-0.57, P = 0.011), respectively. Conclusions: Subjects with systemic inflammation were more insulin-resistant, and in nondiabetic predialysis CKD, IR and systemic inflammation were independently associated with endothelial dysfunction and atherosclerosis.