Date of Award

January 2015

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Olga Laur

Subject Area(s)

Medicine

Abstract

Aims: Renal dysfunction (RD) is a potent risk factor for death in patients with cardiovascular disease. This relationship may be causal since experimentally induced RD produces findings such as myocardial necrosis and apoptosis in animals. Cardiac transplantation provides an opportunity to investigate this hypothesis in humans; if direct myocardial damage is principally responsible for the substantial risk associated with RD, this risk should be transferable from a donor with RD to the recipient via the allograft.

Methods and Results: Cardiac transplantations from the UNOS registry were studied (n=23,056). RD was defined as an estimated glomerular filtration rate < 60 ml/min/1.73m2. RD was present in 17.9% of donors and 39.4% of recipients. Donor characteristics that could theoretically result in myocardial damage such as longer ischemic time, older age, diabetes, hypertension, and cigarette use were associated with increased graft failure (p≤0.007 for all). However, donor RD was not associated with graft failure (age-adjusted HR=1.00, 95% CI 0.94-1.07, p=0.92). Moreover, in recipients with RD the highest risk for graft failure occurred immediately post-transplant (0-30 day HR=1.8, 95% CI 1.54-2.02, p<0.001) with subsequent attenuation of the risk over time (30-365 day HR=0.92, 95% CI 0.77-1.09, p=0.33).

Conclusion: The risk associated with RD does not appear to be transferrable from donor to recipient via the cardiac allograft and the risk associated with recipient RD is greatest immediately following transplant. These observations suggest that the non-myocardial aspects of cardio-renal dysfunction are of particular importance in the risk associated with RD.

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This is an Open Access Thesis.

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