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Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Adipokines and their Relation to Endothelial Dysfunction in Patients with Chronic Kidney Disease
Madhusudan Ambarkar1, Srinivasarao V L N Pemmaraju2, Sivakrishna Gouroju3
1PhD Scholar, Department of Biochemistry, Sri Venkateswara Institute of Medical Sciences (SVIMS) , Alipiri Road, Tirupati, Andhra Pradesh, India .
Insights
Chronic kidney disease (CKD) is linked to cardiovascular issues due to altered adipokines and inflammation. Increased interleukin-6 (IL-6) in CKD negatively impacts nitric oxide (NO) levels, contributing to endothelial dysfunction.
Area of Science:
- Nephrology
- Cardiology
- Biochemistry
Background:
- Chronic Kidney Disease (CKD) patients face elevated cardiovascular disease (CVD) risks.
- Reduced nitric oxide (NO) bioavailability and inflammation are key factors in CKD-associated endothelial dysfunction (ED) and CVD.
- Adipose tissue-derived factors (adipokines) are implicated in inflammation and ED within CKD.
Purpose of the Study:
- To compare adipokine, inflammatory, and ED marker concentrations in CKD patients versus healthy controls.
- To investigate the associations between adipokines, inflammation, and ED in CKD patients across different disease stages.
Main Methods:
- 120 CKD patients were categorized into three groups based on Glomerular Filtration Rate (GFR) (Stages I-V), alongside 40 healthy controls.
- Measurements included adiponectin, leptin, Interleukin-10 (IL-10), Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) via ELISA, high-sensitivity C-reactive protein (hsCRP) via immunoturbidimetry, and NO via Griess method.
- Statistical analyses included Mann-Whitney U, ANOVA, Kruskal-Wallis, Spearman's rank correlation, and linear regression.
Main Results:
- CKD patients exhibited significantly higher leptin, IL-6, TNF-α, IL-6/IL-10 ratio, and hsCRP, with lower adiponectin, IL-10, and NO compared to controls (p<0.05).
- Within CKD groups, adiponectin, leptin, IL-6, IL-6/IL-10 ratio, and TNF-α increased, while IL-10 decreased progressively with declining GFR (p<0.05).
- Interleukin-6 (IL-6) showed a significant negative correlation with NO (r=-0.557; p=0.005) and a negative association in linear regression (B±SE=-0.038±0.11; p=0.002) in advanced CKD stages.
Conclusions:
- Altered adipokine profiles in CKD, progressing with renal dysfunction, contribute to inflammation.
- This inflammatory state, coupled with adipokine changes, exacerbates endothelial dysfunction (ED).
- The study highlights a pathway linking altered adipokines and inflammation to ED and cardiovascular events in CKD patients.
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/1.73m(2) (stage I, II), group II (n=40) had 15-59 ml/min/1.73m(2) (stage III, IV) and group III (n=40) had <15 ml/min/1.73m(2) (stage V). Forty healthy subjects served as controls. Adiponectin, Leptin, Interleukin-10 (IL-10), Interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) 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-α, 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-α 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.
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