Biomarkers of Cardiovascular Disease in Renal Transplant Recipients

Abstract

Background:
Cardiovascular disease is a leading cause of premature mortality in renal transplant recipients. Predicting the risk of future cardiovascular events in this patient cohort is challenging due to the prevalence of non-traditional risk factors. Biomarkers of cardiovascular disease have been demonstrated to improve the accuracy of cardiovascular prediction models in the general population, but their potential utility in renal transplant recipients is unclear.

Aims and Objectives:
This thesis aims to assess whether established biomarkers of cardiovascular disease are predictive of adverse outcomes in stable renal transplant recipients.

Patients and Methods:
A cohort of 379 renal transplant recipients were studied. Prospective follow-up data (median of 16.2 years) were available for adverse outcomes including mortality, major adverse cardiovascular events (MACE) and graft loss. C-reactive protein (CRP), troponin T (TnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and soluble ST2 (sST2) were measured from stored plasma/serum samples and investigated for an association with these outcomes. Discrimination metrics were derived to quantify the incremental value of adding biomarker concentrations to existing cardiovascular risk prediction models.

Results:
Cardiovascular disease was the leading cause of mortality in the cohort and accounted for 47% of deaths. Malignancy (28%) and infection (22%) were also common causes of mortality. All of the biomarkers associated with all-cause and cardiovascular mortality, though the strength of association varied considerably. CRP, TnT and NT-proBNP were also associated with MACE. Overall, TnT and NT-proBNP moderately improved the accuracy of risk prediction models. Several biomarkers were associated with secondary outcomes including death-censored graft loss and infection-related mortality, highlighting a potential role for these biomarkers outside of cardiovascular risk prediction.

Conclusions:
Data from these studies suggest that established biomarkers of cardiovascular disease may have a role in predicting adverse outcomes in renal transplant recipients, including several which are unrelated to cardiovascular disease.

Date of Award	Dec 2019
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	NI Kidney Research Fund
Supervisor	Peter Maxwell (Supervisor) & Christopher Cardwell (Supervisor)