Association between Serum Indoxyl Sulfate Levels and Endothelial Function in Non-Dialysis Chronic Kidney Disease.

Chih-Hsien Wang,Jen-Pi Tsai,Bang-Gee Hsu,Yu-Hsien Lai,Yu-Li Lin,Chiu-Huang Kuo

doi:10.3390/toxins11100589

Abstract

Indoxyl sulfate (IS), a product metabolized from tryptophan, is negatively correlated with renal function and cardiovascular diseases in patients with chronic kidney disease (CKD). We investigated the association between serum IS levels and endothelial function in patients with CKD. Fasting blood samples were obtained from 110 patients with stages 3–5 CKD. The endothelial function, represented by vascular reactivity index (VRI), was measured non-invasively using digital thermal monitoring. Serum IS levels were determined using liquid chromatography–mass spectrometry. Twenty-one (19.1%), 36 (32.7%), and 53 (48.2%) patients had poor (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), and good (VRI ≥ 2.0) vascular reactivity. By univariate linear regression analysis, a higher prevalence of smoking, advanced age, higher systolic, and diastolic blood pressure (DBP), elevated levels of serum phosphorus, blood urea nitrogen, creatinine, and IS were negatively correlated with VRI values, but estimated glomerular filtration rate negatively associated with VRI values. After being adjusted by using multivariate stepwise linear regression analysis, DBP and IS levels were significantly negatively associated with VRI values in CKD patients. We concluded that IS level associated inversely with VRI values and had a modulating role in endothelial function in patients with stages 3–5 CKD.

Highlights

For a majority of patients with chronic kidney disease (CKD), cardiovascular disease (CVD) is the main cause of mortality not fully related to traditional risk factors such as age, hypertension (HTN), and diabetes mellitus (DM), and non-traditional factors including inflammation, abnormal bone and mineral metabolism, and endothelial damage or dysfunction [1,2]
With respect to renal function defined by CKD stage, there were more patients at more advanced CKD stages with lower vascular reactivity index (VRI) values (p < 0.001)
In a long-term observational study, which presents with endothelial dysfunction as andysfunction early marker, in thedeteriorated uremic state;inthus, atherosclerosis, which presents with endothelial asdeteriorated an early marker, the uremic state; atherosclerosis is considered as the main cause of CVD in patients with CKD [15]

Summary

Introduction

For a majority of patients with chronic kidney disease (CKD), cardiovascular disease (CVD) is the main cause of mortality not fully related to traditional risk factors such as age, hypertension (HTN), and diabetes mellitus (DM), and non-traditional factors including inflammation, abnormal bone and mineral metabolism, and endothelial damage or dysfunction [1,2]. Increasing evidence indicates that endothelial dysfunction can be measured non-invasively and is linked to adverse outcomes in patients with CKD [7,8]. Naghavi et al conducted a study in a registry of 6084 patients comparing different methods of measuring functional endothelial dysfunction, including digital thermal monitoring (DTM), flow-mediated dilatation, peripheral arterial tonometry, and photoplethysmography [11]. Digital thermal monitoring was shown to provide equivalent ability of measurements compared to other methods and was easier in terms of use and applicability to medical staff or patients [11]

Methods

Results

Conclusion