A prospective study of the effects of renal transplantation on uraemic cardiomyopathy using cardiac magnetic resonance imaging: the RETRACT study

Pickup, Luke Christopher (2024). A prospective study of the effects of renal transplantation on uraemic cardiomyopathy using cardiac magnetic resonance imaging: the RETRACT study. University of Birmingham. Ph.D.

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Abstract

Background: There is an inverse graded relationship between cardiovascular risk and renal function, with the greatest risk observed in those with end-stage kidney disease. This relationship is attributed to the development of uraemic cardiomyopathy which is characterised by the development of myocardial fibrosis, left ventricular hypertrophy and both diastolic and systolic dysfunction. Following renal transplantation this risk reduces dramatically a finding which is often attributed to positive cardiovascular remodelling. At present, however, this has not been demonstrated in a prospective adequately powered study employing cardiac magnetic resonance imaging.

Objectives: To establish if the features of uraemic cardiomyopathy are reversible following renal transplantation.

Participants: 50 renal transplant recipients recruited from local transplant waiting list. 20 transplant-listed control participants with end stage kidney disease not scheduled for live donor transplantation.

Methods: Participants had demographic and CMR parameters recorded at baseline and follow-up at 12- 24 months. Renal transplant recipients were studied within a one-month period prior to transplantation. Measures of left ventricular mass, volume, systolic and diastolic function, myocardial fibrosis and biochemical parameters were all recorded both before and after transplantation.

Results: There were significant reductions in LVM observed in transplant recipients compared to control patients (between group mean difference -18.76g 95%CI [-30.46 - -7.05] P=0.002). There was also a significant reduction in LVMI in the transplant group compared to controls (between group mean difference -11.37g/m2 95%CI [-18.49 - -4.25] P=0.002). There were no significant differences observed in measures of either systolic or diastolic function. In terms of native T1 mapping times, there were significant reductions observed in transplant recipients compared to controls, in the global average of all segments in the mid ventricular slice (between group difference -34.37ms 95%CI [-61.01 - -7.74] P=0.01. There were no significant changes in T2 times between groups. Analysis of biochemical parameters indicated significant differences in multiple parameters including haemoglobin (18.39 g/l 95%CI[7.12- 29.66]P<0.001), NTproBNP (x0.10[0.05-0.22]P<0.001), and marker of chronic kidney disease – mineral bone disorder; parathyroid hormone (x0.40 95%CI[0.17 – 0.93]p+0.035, phosphate (-0.28 mmol/L [-0.41 - -0.16]P<0.001) and Vitamin D (31.54 nmol/L 95%CI(16.03 -47.05)P<0.001).

Conclusion: The RETRACT study has shown that the features of uraemic cardiomyopathy are reversible following renal transplantation. This works adds to the current understanding of uraemic cardiomyopathy and provides a rationale for the development of targeted therapies aimed at reversing cardiovascular remodelling in those in whom transplantation is not a treatment option.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):