title: Functional magnetic resonance imaging in patients with kidney failure: optimising imaging biomarkers
Creators: name: Rankin, Alastair J.
Publisher: name: University of Glasgow
Year: 2022
Subjects: subject: End-stage kidney disease, haemodialysis, cardiovascular, magnetic resonance imaging, left ventricular hypertrophy.

description: Introduction: The prevalence of kidney failure is increasing globally. Patients with kidney failure experience a vastly increased risk of cardiovascular disease and premature death, which is incompletely offset with current kidney replacement therapies. The development of reliable biomarkers in kidney failure could allow novel therapeutics to be more readily trialled in patients with kidney failure due to enhanced patient selection, reduced participant burden and reduced trial duration and cost. The present thesis utilises 6 distinct studies to examine imaging biomarkers applied to 2 sub-populations of patients with kidney failure. Firstly, I explore several imaging techniques assessing the excess cardiovascular risk observed in patients on dialysis (studies 1-4). Secondly, I examine the utility of renal MRI to investigate kidney transplant dysfunction (studies 5, 6). Methods and Results: 1. Global longitudinal strain on cardiovascular MRI. In a retrospective study of 215 participants with kidney failure, left ventricular global longitudinal strain on cardiovascular MRI associated with all-cause mortality, independent of baseline clinical variables and future renal transplantation. 2. Effect of haemodialysis on native T1 mapping. In a prospective study of 26 patients undergoing regular haemodialysis, acute changes in cardiac volumes and myocardial composition were detectable on 3T cardiovascular MRI following a single session of haemodialysis with fluid removal. 3. Radial-VIBE MRI for the detection of vascular calcification. In a prospective study of 96 individuals with kidney failure (24 haemodialysis, 72 transplant), a radialVIBE sequence on MRI was subjectively able to detect thoracic aortic calcification. However, significant bias existed with respect to quantification of calcification volume, with MRI over-estimating volume when minimal calcification was present and under-estimating it at greater volumes. Improvements in radial-VIBE image quality are necessary, and until then CT should remain the primary modality for assessing vascular calcification in clinical practice. 4. Myocardial extracellular volume by contrast enhanced CT. In a prospective study of 23 participants on regular haemodialysis there was no correlation between extracellular volume on CT and myocardial native T1 (a surrogate for myocardial fibrosis). 5. Different regions of interest for the analysis of multiparametric renal MRI. In a pooled study consisting of 40 participants (10 healthy volunteers, 10 patients with left ventricular systolic dysfunction and 20 renal transplant recipients) comparing different regions of interest (ROI) for the analysis of renal MRI, it was found that manually drawn ROIs delineating the cortex or in a representative area of cortex could be used interchangeably, with acceptable inter-observer reproducibility. 6. Multiparametric renal MRI for the investigation of renal transplant dysfunction. In a study of 28 participants (20 with complete data) that was stopped prematurely due to the COVID-19 pandemic, there was no correlation between any renal MRI variable and the percentage of renal cortex containing fibrosis. Conclusion: There is a clear clinical need for the development and validation of reliable biomarkers for patients with kidney failure. However, the results of the present thesis suggest that, in their present form, neither functional MRI for the identification of cardiovascular disease in patients undergoing dialysis, nor renal MRI in patients with transplant dysfunction, are ready for implementation into clinical trial research protocols or clinical practice.