Mahmoud, Huda S.
(2022)
The application of cardiac and renal imaging in the assessment of acute kidney injury and chronic kidney disease.
PhD thesis, University of Nottingham.
Abstract
Despite pathological diversity, chronic kidney disease and acute kidney injury are inextricably linked in a perpetual cycle of renal and cardiovascular damage and decline.
In the 21st century, CKD is considered a global health crisis; comparatively, AKI is an emergent and escalating healthcare concern, the true scale of which is still to be established. Persons with CKD experience more episodes of AKI compared to individuals without established renal disease. Equally, those afflicted by AKI have an increased prospect of advancing to CKD and ESRF than those not afflicted by AKI.
Within CKD and AKI populations, the capability to predict progressive renal function decline remains elusive. In CKD populations, previous renal trajectory can be used to predict future renal decline. However, historic serum biochemistry data is often incomplete or absent. Predicting renal outcomes in the AKI population is even more challenging; in many, there is an apparent biochemical recovery on the background of significant renal parenchymal damage. As a result, insidious and undetected renal disease often develops to CKD and ESRF, as does the secondary cardiovascular sequelae of renal disease.
CKD and AKI are associated with a significant risk of developing end-stage renal failure and are connected by an increased cardiovascular burden. In particular, persons with CKD are more likely to die of cardiovascular disease than reach end-stage renal failure. Most patients with ESRF have established and substantial cardiovascular disease that continues to amass on renal replacement therapy. Equally, AKI episodes are associated with higher all-cause and cardiovascular mortality rates, that remains for many years after hospital discharge.
The work in this thesis aims to develop cardiac and renal imaging in the assessment of individuals with renal disease. The first half of the thesis is dedicated to understanding cardiovascular morbidity in acute and chronic renal replacement therapy.
Firstly, thirteen individuals requiring acute RRT for AKI were assessed using intradialytic echocardiography and speckle-tracking software. Acute reductions in cardiac function in response to therapy were identified in all participants. The pattern of segmental LV dysfunction was suggestive of subclinical myocardial ischaemia and persisted after the dialysis cessation.
Secondly, a post hoc analysis study of ten individuals requiring chronic haemodialysis was performed. Assessments of systolic and diastolic dysfunction were produced from intradialytic cardiac magnetic resonance images. Systolic and diastolic dysfunction were independently, adversely affected by dialysis and these deteriorations were related with ultrafiltration volume and rate.
The second half of the thesis relates to the application of renal multiparametric magnetic resonance imaging to the understanding of pathophysiological processes in AKI and CKD.
The initial multiparametric study involved 49 participants; 25 had stable CKD stage 3-4 and underwent serial renal functional and structural multiparametric magnetic resonance imaging(MRI). Multiparametric MRI successfully differentiated between healthy and CKD cohorts. The CKD population showed excellent reproducibility of MR measures. The functional and structural MR measures evidenced smaller renal volumes, reduced perfusion, increased T1 values (suggesting increased inflammation/fibrosis) but no change in T2* values (markers of renal parenchymal hypoxia). Importantly, biochemical and histological measures of renal disease correlated with MR measures. Longitudinally there was some evidence to suggest the detection of pathophysiological changes in spite of biochemical evidence to suggest clinical stability.
The final multiparametric MRI study assessed ten individuals with AKI stage 2/3. This study was the first to utilise multiparametric MRI to evaluate the pathophysiology of AKI by assessing renal function and structure both at the time of AKI and longitudinally into the post-AKI recovery period. At the time of AKI injury, renal volume increased, renal perfusion declined, increased T1 values (suggesting increased inflammation) and decreased T2* values, suggesting a decline in renal tissue hypoxia. Biochemical recovery occurred within 90-days; at this point, multiparametric results revealed a regression to normal physiology but not complete recovery. Renal volumes were still enlarged, a reduction in renal perfusion remained and increased markers of inflammation were still present. Many participants’ multiparametric measures had normalised at one year, but evidence of altered pathophysiology remained in others.
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