Arginine Metabolites as Biomarkers of Myocardial Ischaemia, Assessed with Cardiac Magnetic Resonance Imaging in Chronic Kidney Disease.

Ranjit J Shah,Joseph B Selvanayagam,Sara Tommasi,Arduino A Mangoni,Randall Faull,Jonathan M Gleadle

doi:10.3390/biom11030416

Abstract

(1) Background: Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Myocardial oxygenation and perfusion response to stress, using oxygen-sensitive cardiovascular magnetic resonance (OS-CMR) and stress T1 mapping respectively, are impaired in CKD patients with and without known coronary artery disease (CAD). Endothelial dysfunction, assessed by circulating levels of asymmetric dimethylarginine (ADMA) and homoarginine (HMA), promotes atherosclerosis. We hypothesized that in CKD patients, worsening endothelial dysfunction is associated with worsening myocardial oxygenation and perfusion as assessed by change in OS-CMR signal intensity (Δ OS-CMR SI) and stress T1 (ΔT1) values. (2) Methods: 38 patients with advanced CKD underwent cardiovascular magnetic resonance (CMR) scanning at 3 Tesla. OS-CMR and T1 mapping images were acquired both at rest and after adenosine stress and analyzed semi-quantitatively. Serum ADMA and HMA concentrations were assessed using mass spectrometry. (3) Results: There was no significant correlation between Δ OS-CMR SI and ADMA or HMA. Interestingly, there was a significant negative correlation seen between Δ T1 and ADMA (r = −0.419, p = 0.037, n = 30) but not between Δ T1 and HMA. (4) Conclusions: Stress T1 response is impaired in CKD patients and is independently associated with higher circulating ADMA concentrations.

Highlights

Endothelial dysfunction is typically characterized by reduced nitric oxide (NO) synthesis, which significantly contributes to the development of atherosclerotic Cardiovascular disease (CVD) and to deterioration in renal function [5,6,7]
We studied 38 patients with chronic kidney disease (CKD) enrolled at Flinders Medical Centre (FMC) and the
This study demonstrates that there is a significant association between asymmetric dimethylarginine (ADMA) concentrations and Stress T1 response in CKD patients

Summary

Introduction

Cardiovascular disease (CVD) is common in patients with advanced chronic kidney disease (CKD) with estimates that up-to half of patients with severe CKD have significant coronary artery disease, heart failure or left ventricular hypertrophy [1,2,3]. Traditional cardiovascular risk factors such as hypertension and hypercholesterolemia, common among advanced CKD patients, can only partly explain the increased susceptibility to CVD in this group [4]. All known cardiovascular risk factors seen in CKD patients are associated with endothelial dysfunction, a key player in the pathogenesis of CVD together with. Biomolecules 2021, 11, 416 inflammation and atherosclerosis. Endothelial dysfunction is typically characterized by reduced nitric oxide (NO) synthesis, which significantly contributes to the development of atherosclerotic CVD and to deterioration in renal function [5,6,7]. Endothelial NO synthase (eNOS) catalyzes the conversion of L-arginine (ARG) and L-homoarginine (HMA)

Methods

Discussion

Conclusion