Circulating miRNAs and Vascular Injury Markers Associate with Cardiovascular Function in Older Patients Reaching End-Stage Kidney Disease.

Qiao Zhao,Sabine J L Nooren,Anton Jan Van Zonneveld,J Wouter Jukema,Ton J Rabelink,Laurien E Zijlstra,Jos J M Westenberg,Noeleen C Berkhout-Byrne,Marjolijn Van Buren,Roel Bijkerk,Lucia J M Kroft,Simon P Mooijaart

doi:10.3390/ncrna8010002

Abstract

The prevalence of end-stage kidney disease (ESKD) is rapidly increasing and mostly occurring in patients aged 65 years or older. The main cause of death in these patients is cardiovascular disease (CVD). Novel markers of vascular integrity may thus be of clinical value for identifying patients at high risk for CVD. Here we associated the levels of selected circulating angiogenic miRNAs, angiopoietin-2 (Ang-2) and asymmetric dimethylarginine (ADMA) with cardiovascular structure and function (as determined by cardiovascular MRI) in 67 older patients reaching ESKD that were included from ‘The Cognitive decline in Older Patients with End stage renal disease’ (COPE) prospective, multicentered cohort study. We first determined the association between the vascular injury markers and specific heart conditions and observed that ESKD patients with coronary heart disease have significantly higher levels of circulating ADMA and miR-27a. Moreover, circulating levels of miR-27a were higher in patients with atrial fibrillation. In addition, the circulating levels of the vascular injury markers were associated with measures of cardiovascular structure and function obtained from cardiovascular MRI: pulse wave velocity (PWV), ejection fraction (EF) and cardiac index (CI). We found Ang-2 and miR-27a to be strongly correlated to the PWV, while Ang-2 also associated with ejection fraction. Finally, we observed that in contrast to miR-27a, Ang-2 was not associated with a vascular cause of the primary kidney disease, suggesting Ang-2 may be an ESKD-specific marker of vascular injury. Taken together, among older patients with ESKD, aberrant levels of vascular injury markers (miR-27a, Ang-2 and ADMA) associated with impaired cardiovascular function. These markers may serve to identify individuals at higher risk of CVD, as well as give insight into the underlying (vascular) pathophysiology.

Highlights

Chronic kidney disease (CKD) has a worldwide prevalence of about 10%, which is rapidly increasing [1–3]
This study revealed that, in older patients reaching end-stage kidney disease (ESKD), vascular injury markers are associated with markers of cardiovascular structure and function
This could possibly be explained by the Windkessel effect of the arteries that is compromised in patients with arterial stiffness

Summary

Introduction

Chronic kidney disease (CKD) has a worldwide prevalence of about 10%, which is rapidly increasing [1–3]. The high incidence of CVD in ESKD relates to traditional CVD-risk factors such as hypertension and diabetes (often present in CKD patients), and CKD-specific alterations that may cause (micro)vascular dysfunction: increases in circulating levels of waste products such as uremic toxins (e.g., asymmetric dimethylarginine (ADMA), altered renal endocrine factors (renin-angiotensin-aldosterone-system, vitamin D, erythropoietin), anemia, serum calcium and phosphate levels [16–18]. These nephrogenic factors predispose these patients to eventually develop abnormal cardiovascular structure or function [14–19], as defined by arterial stiffness (pulse wave velocity (PWV)), systolic heart function (cardiac index (CI) and the ejection fraction (EF)), and eventually heart failure [20,21]. The exact underlying pathophysiological mechanisms behind the highly frequent impaired cardiovascular structure and function in ESKD patients remain unclear

Objectives

Results

Conclusion