Adipokines and their Relation to Endothelial Dysfunction in Patients with Chronic Kidney Disease

摘要

Introduction: Chronic Kidney Disease (CKD) patients are at high risk of cardiovascular diseases (CVDs). Reduced nitric oxide (NO) bioavailability is a key element in connecting kidney disease to endothelial dysfunction (ED) and cardiovascular (CV) complications. Further, inflammation is implicated in ED in CKD. Besides these, adipose tissue factors were thought to have a role in inflammation and ED in CKD. Aim: It is proposed to evaluate the concentration changes of adipokines, inflammatory and ED markers in CKD patients compared to healthy controls. Further, to assess the associations between adipokines, inflammation and ED in CKD patients. Materials and Methods: A total of 120 CKD patients were included and classified into 3 groups based on Glomerular filtration rate (GFR). Group I (n=40) patients had a GFR between 60-119 ml/min/1.73m2 (stage I, II), group II (n=40) had 15-59 ml/min/1.73m2 (stage III, IV) and group III (n=40) had <15 ml/min/1.73m2 (stage V). Forty healthy subjects served as controls. Adiponectin, Leptin, Interleukin-10 (IL-10), Interleukin-6 (IL-6), tumour necrosis factor-a (TNF-a) were estimated by ELISA. High sensitivity C-reactive protein (hsCRP) was estimated by immunoturbidimetry and NO by Griess method. Statistical Analysis: Mann-Whitney U test was used to compare the difference in variables between controls and CKD patients. One-way ANOVA Kruskalwallis test was used for comparison of variables between groups in CKD patients. Spearman?s rank correlation was used to explore the associations between variables. Simple univariate linear regression analysis was used to predict the value of variable from another variable. Results: A significant increase in leptin, IL-6, TNF-a, IL-6/IL-10 ratio, hsCRP and decrease in adiponectin, IL-10, NO was observed in CKD patients compared to controls (p<0.05). In CKD patients, adiponectin, leptin, IL-6, IL-6/IL-10 ratio, TNF-a were significantly increased and IL-10 levels were decreased from group I to group III (p<0.05). In group III CKD patients IL-6 showed a significant negative correlation with NO (r=-0.557; p=0.005). In linear regression analysis also, IL-6 showed a significant negative association with NO (B±SE=-0.038±0.11; p=0.002) in CKD patients. Conclusion: The present study demonstrates that adipokine levels are altered from initial to final stages of CKD due to renal dysfunction which in association with an exaggerated inflammation may contribute to the ED and CV events.