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Renal transplantation has been shown to not only improve the quality of life, but also survival in recipients (1). However, with the increasing number of people joining the waiting list, there is increasing pressure to carefully screen patients as to their suitability as potential recipients. Patients with end-stage renal disease (ESRD) have an excessive risk of dying of cardiovascular causes compared to the general population (2), and this seems to mirror the increased incidence of coronary artery disease (CAD) in patients with ESRD. Consequently, cardiac evaluation prior to renal transplantation has been a pillar of this evaluation process. But the best method for screening potential recipients remains a subject of debate.

It is well known that the burden of cardiovascular risk is disproportionably high in patients with advanced chronic kidney disease (CKD) and ESRD compared to the general population (3). Coronary artery calcification (CAC) is often an early process in CKD and has been noted in a significant percentage of patients before ESRD (4).This likely reflects a combination of traditional risk factors compounded by special risk factors associated with advanced renal disease such as uremia, hyperphosphatemia anemia and left ventricular hypertrophy (5). These factors contribute to the increased risk of myocardial infarction and death in patients with ESRD such that the risk of having an acute myocardial infarction approaches 75% after a patient has been on dialysis for 3 or more years (6).

Approximately 40% of ESRD patients will have angiographic evidence of significant coronary artery stenosis (>70%) and those patients with significant stenosis have increased risk of acute myocardial infarction and death (7). It would seem to logically follow that careful cardiac screening before transplantation would improve survival after renal transplantation but it is still a subject of debate as to whether the CAC noted in advanced CKD is the true cause of the increased risk of cardiovascular mortality or perhaps more of a marker of those patients at risk (8). Consequently, the risk of contrast nephropathy and the increased risk of mortality after coronary revascularization surgery (9) should not be easily dismissed since the data confirming prolonged survival after cardiac interventions in ESRD patients are lacking. Only one randomized controlled trial seemed to show an improvement in outcomes after revascularization versus medical management of diabetic patients with significant coronary artery lesions before renal transplantation (10). However, this trial may be difficult to interpret since the trial was relatively small, had increased use of short-acting calcium channel blockers in the medically treated group and suboptimal use of aspirin.

The article by Patel et al., in this issue of AJT (11), challenges the premise that cardiovascular testing before renal transplantation improves cardiovascular mortality outcomes after transplant. Their article even suggests that cardiac testing may only serve as a barrier to being placed on the waitlist. Their study design was a prospective, observational study examining their transplant center's registry over a 4-year period in Western Scotland. Initially, the planned study was to compare all candidates by both noninvasive methods and then follow this with coronary angiography; however, this was deemed unacceptable by referring nephrologists, cardiologists and their institutional review board and so invasive evaluations occurred only on a ‘selected basis’ when requested. Obviously, this may have introduced bias depending on which referring physician evaluated a patient as to whether they would need coronary angiography and/or intervention.

Noninvasive evaluation included standard Bruce protocol treadmill exercising (ETT) and cardiac magnetic resonance (CMR) scanning. CMR was used to both evaluate left ventricular volumes and to assess the degree of CAC.

Criteria for coronary angiography were age >50 years, positive ETT (either EKG or symptomatic), ESRD secondary to diabetes and abnormal CMR findings. Coronary angiography was recorded into fairly standard categories based on whether the patients had occlusive disease (>75% stenosis) or nonocclusive disease and the number of vessels affected. However, no mention is made of the criteria that led to 17 patients having an intervention (either bypass grafting or percutaneous stenting) being done. It is interesting to note that 4 of the 13 patients who underwent percutaneous coronary intervention (PCI) had nonocclusive disease by angiography but further description of the indications for PCI in this subgroup was not described.

During this 4-year study period, over 300 patients were consecutively evaluated and 221 were eventually listed. Survival time was compared between those who received a renal transplanted versus those who did not. Their study noted a similar risk for cardiovascular complications after transplant despite cardiovascular testing and interventions in ‘high-risk’ patients before renal transplantation was performed. However, before drawing conclusions about our own patient populations, the reader must bear in mind several potential problems of the study. First, Scotland is a predominantly Caucasian population and so other ethnicities may be underrepresented, which may have a bearing on the rates of CAD in their study. Second, almost one-third of all potential recipients (n = 78) were excluded from the waiting list and perhaps cardiovascular risk factors identified during the evaluation process may have prevented many from being waitlisted. It was evident that those who were not waitlisted were older, diabetic, less mobile and more likely to suffer from ischemic heart disease but the exact causes for not being placed on the waitlist were not known to the authors. It can be surmised that those patients had excessive burden of comorbid conditions that may have contributed to their being deemed inappropriate candidates for revascularization procedures. This may explain why a large number of potential recipients (n = 117) were able to complete over 6 min of the Bruce Exercise stress testing, suggesting a bias toward younger patients with a decreased burden of underlying cardiovascular disease. This seems to be supported by the fact that those who were eventually listed were younger and less likely to have obstructive CAD (see Table 1). As has been noted in other studies examining outcomes of waitlisted recipients in Canada, the older the age the higher the risk of cardiovascular disease and death (12). However, by then evaluating the entire cohort the fact that many patients may not have undergone coronary angiography because they were deemed ‘unlistable candidates’ may have skewed the outcomes against those who were ‘listable’ and did not have angiography.

Similar to studies in the United States (13), approximately 34% of patients had significant stenosis of one or more coronary vessels by coronary angiography. However, the rate of either PCI or surgical interventions to correct these lesions was surprisingly low (n = 13) particularly in light of the fact that 34 significant stenosis were identified by angiography. Given the very small numbers, it becomes difficult to draw significant conclusions as to whether these interventions may have indeed conferred a survival benefit in such a small group.

Nonetheless, this study is very provocative and challenges the transplant community to reconsider some of our current practices. First, with the increased risk of contrast nephropathy, what new noninvasive technologies may better aid in screening for occult coronary artery disease. The authors have been instrumental in advancing CMR as a screening tool for coronary disease. Recent advancements in CMR seem to hold great promise for noninvasive screening of patients with coronary artery disease (14,15). However, this needs to be validated in the potential renal transplant recipient. We, the transplant community, need to design large, prospective, multicentered trials that are powered to answer these tremendously important questions asked in this article. What is the best method for cardiac screening before renal transplantation? Does coronary revascularization decrease cardiovascular events in transplant recipients? Will the advent of new anti-proliferative medicines that decrease the risk rate of restenosis after PCI (16) improve the cardiac risk of a patient awaiting the opportunity to receive a renal transplant?

References

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  2. References
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