Katie Lindale, MSc Candidate (Translational Medicine)
Continuous, evidence-based reassessment of clinical guidelines is a cornerstone of translational research and is a major focus when it comes to kidney transplant. Dr. Shamseddin is a Transplant Nephrologist, educator and an active leader in Nephrology and Kidney Transplant initiatives locally, provincially, and nationally. Last Thursday, our class was fortunate to learn about his work towards an improved, evidence-based guideline for asymptomatic heart disease screening in patients waitlisted for kidney transplant.
Coronary artery disease (CAD) is the highest factor for morbidity and mortality among kidney transplant patients, and is highly prevalent in this population in part because of its considerable overlap of risk factors with kidney disease. For example, by year 3 on the waitlist for kidney transplant, up to 16.7% of patients experience a myocardial infarction (MI), otherwise known as a heart attack. The need to properly manage the elevated risk of CAD for these patients is amplified by the fact that cardiovascular disease (CVD) accounts for 30% of mortality in the kidney transplant population.
Current guidelines outline the importance of cardiovascular exclusion criteria for kidney transplant, encourage risk-based, preferentially noninvasive screening options and an emphasis on medical cardio-protection with standard treatments such as statins, aspirin, and beta-blockers. Our class discussion addressed questions relating to the benefits of moving towards noninvasive testing and we learned about Dr. Shamseddin’s evidence-based preference of the utility of dobutamine stress echocardiograms (DSE).
Dr. Shamseddin explained that the research landscape for cardiovascular monitoring in waitlisted kidney transplant patients has changed significantly over the past couple of decades. Even then, invasive testing such as coronary angiogram and cardiac catheterization continue to be recommended for those at higher cardiovascular risk. These forms of invasive tests may introduce an unnecessary risk for patients in the form of contrast nephropathy[3, 5], vascular complications, and add excess cost for the healthcare system. Trends show increases in noninvasive testing for low-moderate risk groups, and continued invasive approaches for those with known risk factors such as diabetes mellitus and atherosclerotic CVD. Our class discussion highlighted that it is necessary to consider whether there could be a more sustainable CAD testing and management strategy.
To tackle these questions during our class discussion, Dr. Shamseddin shared ways in which the presence of renal disease in a patient changes the nature of their CVD, subsequently impacting how they should be treated. With reduced renal function, a patient’s cardiovascular issues and specific microvascular dysfunction may be uniquely affected by urea toxicity, along with phosphate and calcium irregularities. With inflammation and oxidative stress as key drivers for CVD in the setting of kidney disease, research is exploring the avenue of immunomodulatory therapies. A critical angle of optimizing cardiovascular monitoring is the consideration of whether the current testing and treatment strategies are addressing the root of the issue for renal patients.
A clinical trial that focuses on the intersection of kidney disease and CAD indicates that for low-moderate risk patients, invasive cardiovascular testing does not add benefit to the patient and that medical therapeutics combined with a noninvasive testing approach are sufficient for management of CAD. Despite this evidence, it’s challenging to translate findings to waitlisted kidney transplant patients because of the comorbid interactions between CAD, renal disease and other risk factors found in this population. Many trials have exclusion criteria that leads to minimal representation of the waitlisted kidney transplant population. Existing findings provide a foundation on which to build an evidence base relevant to these candidates.
In response to this knowledge gap, Dr. Shamseddin and colleagues are collaborating on a trial called Canadian-Australian Randomised Trial for Screening Kidney Transplant Recipients for CAD (CARSK), with the goal of reducing excess CVD monitoring burden. The purpose of the non-inferiority trial is to establish a patient- and system-level impact of eliminated testing for asymptomatic patients after initial screening for waitlist placement. In addition, to understand the importance of pre-transplantation revascularization of coronary stenoses. A major priority is improving cardiovascular and overall survival outcomes for waitlisted patients, as well as during the critical perioperative period and long-term. Understanding the implications of how current knowledge can be generalized to this population will be invaluable for future screening decisions in this population.
Overall, Dr. Shamseddin highlighted how CAD impacts a patient’s eligibility for kidney transplant and perioperative CAD risk, addressed the disconnect between current guidelines and what the evidence is telling physicians and concluded with specific research avenues and considerations to address these issues. Future directions indicate a need to focus on managing CVD with noninvasive testing and mechanism-targeted therapeutics.
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