High burden of ischaemia suggested to equate to 10% perfusion defect on MPS or 2 segments on stress echocardiography [16] [76].

This is predominantly based on expert opinion, given the paucity of strong evidence. Each centre is encouraged to interpret and adapt this to its patient population.

Suggestions for Future Research

• Are biomarkers e.g. troponin, taken at transplant assessment, able to identify patients at low or high risk of peri-transplant cardiac events?
• Does undergoing an initial anatomical or functional cardiac test as part of transplant assessment improve peri-transplant cardiac outcomes vs. receiving maximum medical therapy alone?
• What is the cost-utility of performing functional or anatomical screening tests prior to transplant listing?
• Do interventions to streamline/shorten the cardiac workup process result in improved patient outcomes (i.e. make screening an urgent set of investigations and urgent treatment to enable faster listing)?
• Do frailty scores and other functional scores identify patients who are not suitable for kidney transplantation or identify patients who benefit from additional cardiac investigations or prehabilitation?
• What are the potential unintended consequences of anatomical screening for cardiovascular disease in asymptomatic patients?

Background

Based on the observation that kidney failure carries a high risk of MACE, and that one of the commonest causes of failure of a kidney transplant is cardiac death of the recipient, it has historically been routine practice to perform non-invasive cardiac investigations for patients being considered for kidney transplantation following an initial clinical assessment.  The intention was to identify potential recipients who would benefit from cardiac revascularisation prior to organ transplantation and those at excess risk of post-transplant cardiac death contraindicating transplantation.  This strategy has been called into question by observational studies that have compared patients subjected to cardiac testing to matched patients who have not undergone such testing, showing similar postoperative outcomes in terms of death and MACE. [1] [2]

The randomised-controlled trial ISCHEMIA-CKD demonstrated that CKD patients, including the subgroups on dialysis and with diabetes, without cardiac symptoms and with moderate to severe ischaemia on a non-invasive test, did not derive a prognostic benefit from coronary angiography followed by revascularisation when compared to guideline-directed medical therapy and lifestyle modification. [3] Furthermore, those randomised to angiography and revascularisation had an increased risk of stroke and the combined safety endpoint of death from any cause or initiation of dialysis.  Some UK centres that have adopted a low rate of cardiac testing have acceptably low rates of adverse cardiac outcomes post-transplantation. [4]

Currently, practice varies between transplant centres in the UK, with a 2021 survey showing that 20 of the 23 adult kidney transplant centres perform non-invasive cardiac investigations for patients based on a local risk stratification protocol, whilst 3 centres did not require patients to undergo further cardiac investigation beyond an ECG +/- echocardiogram in the absence of symptoms.  The most frequent screening investigation was a myocardial perfusion scan (55%), followed by a stress echocardiogram (20%).  In a third of centres, the waiting time for investigations was over 10 weeks. [5]

Most studies examining non-invasive cardiac investigations have compared their utility for identifying significant coronary artery stenosis (usually defined as >70% in a major coronary vessel) with that detected by coronary angiography, given the association between angiographic coronary artery disease and post-transplant cardiac events. [6] [7] [8] [9] Others have assessed how abnormalities on non-invasive cardiac investigations compare to post-transplant outcomes such as survival.  Whilst these investigations may aid the identification of patients at lower risk of having clinically significant coronary artery stenosis, or post-operative cardiac events, there remains uncertainty as to what degree of abnormality requires further intervention, and importantly, if intervention improves patient outcomes, or dictates a degree of cardiac risk that is too great to proceed with transplantation.  Non-invasive investigations may therefore be performed in selected individuals to guide conversations about peri-operative risk or aid optimisation of GDMT, but as performing these tests has not been shown to improve post-transplant outcomes, and acknowledging the high burden of cardiovascular disease without a transplant, they should be used in transplant assessment selectively and with knowledge of local availability and sustainability of resources.  Further, although identification of CAD is usually the focus of testing, other pathologies such as arrhythmias, valvulopathies, heart failure and pulmonary hypertension are relevant to cardiac risk stratification.

The 2022 American Heart Association Scientific Statement on Emerging Evidence on Coronary Heart Disease Screening in Kidney and Liver Transplantation Candidates, endorsed by the American Society of Transplantation, provides a comprehensive overview of studies on various non-invasive cardiac investigations. [10] This guideline has been updated with more recent studies, the results of which are presented in Tables 1-14. Currently, there is no evidence to suggest that one form of non-invasive investigation substantially outperforms another in predicting clinical outcomes for patients.  If a non-invasive cardiac investigation is therefore deemed necessary to inform conversations about peri-transplant risk, the test should be chosen based on local availability and expertise.

Strategies for assessing patients’ perioperative cardiovascular risk are outlined below, including assessment of physical function, frailty, biochemical biomarkers, and non-invasive cardiac tests, followed by a suggested clinical algorithm.

History and Examination

A thorough history and examination should be undertaken initially to rule out underlying cardiac disease.  This assessment should include signs and symptoms of CAD, valvular disease, heart failure, pulmonary hypertension, peripheral arterial disease and also include information on co-morbidities, risk factors for CAD, including obesity, lipid profile, diabetes, smoking and family history, exercise tolerance, quality of life, duration of kidney failure and presence of anaemia.  Patients symptomatic for cardiac disease or those with known significant cardiac history should undergo evaluation by a cardiologist as part of their workup for kidney transplantation.

Electrocardiogram (ECG)

A 12-lead ECG should be performed on all potential candidates undergoing workup for kidney transplantation. The ECG should be reviewed by a suitably qualified clinician, and any clinically significant abnormalities should prompt referral to cardiology team.

Transthoracic echocardiography

Transthoracic echocardiography can be a valuable test in identifying significant cardiac pathology or end-organ damage prompting further optimisation of medical treatment. However, echocardiography departments across the country are inundated with requests and so appropriate and targeted testing is essential.  A TTE may be omitted if all the following are true: resting ECG showing no significant abnormality, no murmurs on cardiac auscultation, no cardiac history or suspicion of new CAD or valvular heart disease, and excellent exercise tolerance (4 metabolic equivalents or above).  Clinicians should be pragmatic in interpreting results. For example, mitral annular calcification typically reflects the duration of haemodialysis, while the degree of left ventricular hypertrophy reflects blood pressure management. Left ventricular function reflects the adequacy of haemodialysis and volume status at the time of the test.  Information provided about right heart function is also relevant to the assessment (refer to pulmonary hypertension section). Aortic stenosis may be present in 6-13% of ESRD patients and can be more challenging to detect clinically in patients with arteriovenous fistulae. [11] Patients found to have significant pathology should be referred to cardiology.  Echocardiography should not be repeated routinely in the absence of significant change in clinical status or examination findings.

Exercise tolerance test

In an exercise tolerance test, the patient is attached to an ECG monitor and exercises on a treadmill or bicycle at progressively increasing workloads as per a standardised protocol.  The ECG is examined for changes suggestive of myocardial ischaemia.  To be diagnostic, a heart rate of 85% of maximum predicted should be achieved. [12]  Studies in kidney transplant candidates show the sensitivity and specificity for CAD on angiography are poor at 35% and 68% respectively, [13] and exercise tolerance tests are frequently not feasible for patients, as many cannot achieve the required workload for a diagnostic test.  Diagnostic results are achieved in under 40% of transplant candidates. [14]

Myocardial Perfusion Scintigraphy

Myocardial perfusion scintigraphy (MPS) is the most commonly performed non-invasive myocardial ischaemia test in the UK.  Pooled analysis of 7 studies estimated a sensitivity of 0.66 and a specificity of 0.75 of MPS for the detection of angiographic CAD (≥70% stenosis) in kidney transplant candidates, [15] with the suboptimal sensitivity and false positives possibly relating to LV hypertrophy and fibrosis confounding the association between perfusion/wall motion abnormalities and epicardial coronary disease.  Despite the suboptimal sensitivity, MPS results have prognostic significance, with studies showing an association between MPS results, MACE and cardiovascular mortality as strong as that of coronary angiography. [9] Even mild perfusion abnormalities may be associated with mortality.  However, although revascularisation is performed in more patients with severe perfusion defects, this does not improve survival. [16] Abnormal MPS may predict increased mortality risk even in the context of nonobstructive CAD, perhaps as a reflection of microvascular disease or diffuse epicardial stenosis. [17] Clinicians requesting these tests should be aware that these cannot normally be used to determine patients’ access to transplantation and rarely identify patients who should be subjected to revascularisation. Therefore, these tests should be requested in specific clinical scenarios rather than by default.

Stress echocardiography

Stress echocardiography can provide both structural and ischaemic evaluation in a single test without radiation. It can be performed with physical exercise or pharmacological stress, though exercise stress is often precluded by physical limitations (especially frailty and musculoskeletal problems) in patients with kidney failure.  It provides direct assessment of myocardial function, including the presence of stress-induced abnormalities that could indicate underlying CAD.  The inability to achieve the target heart rate in dobutamine stress echo may also be a poor prognostic sign. [18] Performing stress echocardiography may be made more difficult by the presence of hypertension or the occurrence of arrhythmias with inotrope infusions in patients with advanced CKD.  Stress echocardiography performance is slightly better than MPS, with a sensitivity of 0.73 and a specificity of 0.88 for CHD, [15] though it remains unsatisfactory for identifying obstructive CAD.

Coronary Artery Calcium Score (CACS)

Coronary artery calcium scoring (CACS) quantifies calcified coronary plaque using low-dose, ECG-gated CT, producing an Agatston score. It is a highly sensitive tool for detecting coronary artery disease, with a negative predictive value of 98%. [19] Higher scores reflect a greater atherosclerotic burden and are associated with increased risk of cardiac events. [20]

In individuals without CKD undergoing primary prevention screening, CACS may support decisions regarding aspirin and statin therapy. However, current UK guidelines do not recommend routine use of CACS for screening asymptomatic individuals. [21]

In pre-dialysis CKD patients, statins are already recommended for cardiovascular prevention, reducing the utility of asymptomatic CACS screening.  In the context of kidney transplant evaluation, although a low CACS may help identify a low-risk group, coronary calcification is found in up to 83% of dialysis-dependent patients [22], limiting its discriminative value in this population.

CT Coronary Angiography (CTCA)

CT coronary angiography (CTCA) is a highly sensitive test for detecting coronary artery disease, including in advanced CKD, with reported sensitivities, in combination with CACS, ranging from 0.93 to 0.99. [23] [24] [25] In patients with stable chest pain without prior history of CAD UK guidelines recommend CTCA as a first-line diagnostic test for coronary disease. [26] However, in CKD, the diagnostic accuracy of CTCA to identify severe coronary artery stenosis is reduced due to blooming artefact caused by heavy coronary calcification. This can lead to overestimation of stenosis, with specificity reported to range from 0.63 to 0.67. [23] [24] As a result, while a normal CTCA can offer reassurance, interpretation of positive findings is more challenging.  Further, there may be concerns regarding the risk of contrast-induced acute kidney injury, particularly in patients being assessed pre-emptively (prior to the initiation of dialysis).

In clinical practice, CTCA may help exclude significant coronary disease in selected cases, though its use must be weighed against the risks of contrast exposure. In the setting of transplant assessment, CACS and CTCA may provide additional prognostic information regarding long-term survival and perioperative cardiovascular risk. [24] However, current evidence does not support their routine use, given the associated costs, radiation exposure, contrast risks (acute kidney injury estimated to occur in 12% [27]) and potential delays in transplant listing. Technical advances including the introduction of photon-counting detector cardiac CT may significantly improve the assessment of calcified coronary arteries as it offers improved spatial resolution at a lower radiation dose, and therefore could play a greater role in the pre-transplant population. [28] [29]

Cardiovascular Magnetic Resonance Imaging (CMR)

Cardiovascular magnetic resonance (CMR) is widely regarded as the gold standard for non-invasive evaluation of cardiac structure and function, and for myocardial tissue characterisation, particularly for detecting myocardial fibrosis. [30] It is especially valuable for functional assessment when echocardiographic windows are limited.

Historically, the use of contrast-enhanced CMR in ESKD was limited due to concerns over nephrogenic systemic fibrosis (NSF) associated with gadolinium-based contrast agents. However, modern macrocyclic gadolinium chelates offer significantly improved kinetic and thermodynamic stability, with a contemporary estimated risk of NSF of less than 0.07%. [31] A recent prospective study with long-term follow-up reported no cases of NSF following the administration of macrocyclic contrast in patients with advanced CKD. [32] As such, contrast-enhanced CMR is now considered safe in ESKD, with the use of reduced-dose protocols further mitigating any residual risk without compromising diagnostic quality. Additionally, non-contrast parametric mapping sequences, including native T1 mapping and post contrast extracellular volume (ECV) quantification can be useful for tissue characterisation and diagnosing infiltrative causes of cardiomyopathy. [33]

CMR is particularly useful in evaluating the aetiology of left ventricular systolic dysfunction (LVSD) and is recommended in patients with heart failure and ESKD. [30] In dialysis-dependent CKD, where echocardiography often reports a ‘speckled’ myocardium, CMR can distinguish between dialysis-associated or hypertensive left ventricular hypertrophy and cardiac amyloidosis—the latter carrying a significantly poorer prognosis.  CMR also allows for quantification of infarct size and both focal and diffuse interstitial fibrosis, the burden of which correlates with increased risk of MACE. [34] [35] [36]

Vasodilator stress perfusion CMR offers superior spatial resolution compared to myocardial perfusion scintigraphy (MPS).  In patients with stage 3 CKD, it has been shown to be safe and to provide incremental prognostic value for predicting MACE beyond traditional risk factors. [37] However, data in ESKD populations remain limited.

Although access to CMR is variable, it is increasingly becoming part of routine clinical practice. Referral should be cardiologist-led to ensure the imaging protocol is tailored to the clinical question and that results are interpreted in the appropriate context.

Cardiopulmonary exercise testing (CPET)

CPET is a dynamic test which has been used for pre-operative risk stratification and allocation of post-operative care prior to major surgery in patients without kidney failure.  It assesses both cardiorespiratory and metabolic responses during sub-maximal and peak exercise, with cardiorespiratory fitness being a strong predictor of all-cause and cardiovascular mortality, independent of age, sex, ethnicity, and co-morbidities. [38] It is considered the gold standard for assessing exercise capacity and objectively determining exercise tolerance. [39] Patients are exercised on a bicycle ergometer or treadmill, allowing for the calculation of maximal aerobic capacity and the anaerobic threshold, defined as the point during exercise at which anaerobic metabolism is used to supplement aerobic metabolism. It also provides information on stress-induced myocardial ischaemia.

Individuals with chronic kidney disease have reduced maximum aerobic exercise capacity, with contributing factors including anaemia, vascular and cardiac dysfunction, and skeletal or muscle metabolic abnormalities, including sarcopenia. [39] Many patients on dialysis cannot achieve V02 peak because of muscle wasting and weakness, rather than cardiorespiratory reserve. [40] Renal transplant can improve CPET parameters and cardiovascular fitness [41]  [42] [43], but it is less clear whether CPET has a prognostic role in screening patients before they join the transplant waiting list.

A 2016 systematic review found insufficient evidence to recommend the use of CPET as a risk assessment method in patients awaiting renal transplant and highlight this as an area for future research. [38] Two further studies suggest that the recognised risk threshold for the Anaerobic Threshold (AT) of 11 ml/kg/min is unlikely to be applicable to kidney transplant patients and a better threshold may be greater than 40% of predicted AT.  However, despite the low ATs recorded in kidney transplant candidates, there were no deaths and even in those high-risk patients, survival was improved by transplant. [44] [45]

Given the low number of studies and the clear survival benefit with renal transplantation, even in those perceived to be high risk, CPET cannot be recommended to assess risk and suitability in this patient cohort.  Furthermore, performing CPET requires significant healthcare resources and is not a cost-effective screening tool for cardiac risk stratification.

Biochemical biomarkers

The use of cardiac biomarkers, such as N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin, for risk stratification in renal transplantation is an area of research interest. While they may have future roles in cardiovascular risk stratification, there is currently insufficient evidence to recommend their routine use prior to transplantation.

NT-proBNP is the prohormone of BNP and is released by cardiac myocytes in response to stretch and stress and could vary depending on patient’s fluid balance.  NT-proBNP is renally cleared, and levels rise with worsening kidney function.  Despite this, in euvolemic, asymptomatic patients on dialysis, NT-proBNP levels are associated with increased cardiovascular risk. [46] [47] NT-proBNP measured just prior to kidney transplantation associates with post-transplant survival and cardiac events; [48] however, it has not been determined whether a specific threshold or measurement at transplant assessment can identify patients with a suitably low risk of cardiac events who do not require further investigation.

Troponin T (cTnT) levels prior to transplant are associated with the risk of post-transplant death/cardiac events, independent of cardiovascular risk factors. Elevated post-transplant cTnT is associated with reduced patient survival, whereas normalisation of cTnT post-transplant is associated with a reduced risk. [49] Troponin I did not predict cardiovascular events following liver transplantation. [50] Further studies examining troponin I in kidney transplant candidates are awaited.

Assessments of Functional Capacity and Frailty

Functional capacity and frailty metrics include a six-minute walk test, observing patients climbing a flight of stairs, the Duke Activity Status Index (DASI) and frailty assessments such as the Clinical Frailty (Rockwood) score.  These have been examined in general populations undergoing non-cardiac surgery [51] [52], but how these indices could be used to identify patients at higher risk of cardiac disease in the setting of transplantation is the subject of ongoing research.  Whilst there is insufficient published evidence to suggest a threshold or ‘cut-off’ point at which cardiac risk becomes too high, an assessment of functional capacity could be included as part of a holistic assessment to aid identification of those who would benefit from further cardiac testing.  As patients may misreport their functional capacity, it is reasonable for transplant units to use a variety of assessment tools to ensure accurate documentation of functional capacity, similar to that in elective general surgery.

Functional tests are summarised by the UK Centre for Elective Care and include the incremental shuttle walk test (ISWT), the 6-minute walk test (6MWT), the one-minute sit-to-stand test (STS) and the Timed Up-and-Go test. [53] [54] These have the advantage of being low-cost and potentially performed as part of the pre-operative outpatient appointment.  These tools are often used in elective (non-transplant) surgery to attempt to predict unfavourable outcomes, not just those related to cardiac disease.  The evidence for the use of functional assessments in kidney transplant populations is growing, but has not yet been sufficient to lead to large-scale practice changes.  Centres may choose to extrapolate findings from non-transplant surgery as part of their assessment process, but current data do not support them as a sole determinant of fitness for transplantation.  Poorer performance on these tests is modestly associated with increased rates of postoperative complications in non-transplant surgery, and this finding may prompt additional testing.  Some of the more frequently used tests and scores are discussed below.

MACE Risk Prediction Tools

A number of risk-prediction tools are available to estimate the long-term risk of MACE in kidney transplant recipients, but they do not compare this risk with that of remaining on dialysis. [55] [56] [57] Comparison of survival rates between dialysis and kidney transplantation at 1 and 3 years has been studied using US registry data, leading to the development of an online calculator for individual patient risk prediction (https://ichoosekidney.emory.edu/). [58] Overall, the data confirm the survival advantage of kidney transplantation, although there may be unquantifiable selection bias in favour of transplantation.  The calculator may underestimate the risk for the recipient receiving extended-criteria donor kidneys.

Revised Cardiac Risk Index

The Revised Cardiac Risk Index (RCRI) is a calculator that predicts the risk of cardiac complications after non-cardiac surgery based on patient and surgical factors.  It is commonly used in non-transplant surgical settings but performs less well at predicting MACE in ESKD patients undergoing elective non-transplant surgery. [59] The RCRI can be used to estimate perioperative risk but should not be used as a decision-making tool for transplant suitability.

Gait speed

Gait speed can predict outcomes on the transplant waiting list and post-kidney transplant when performed as part of a short physical performance battery. [60] [61] [62] In one observational study, slower gait speed at transplant assessment was associated with increasing mortality from time of assessment, increasing prevalence of cardiovascular events, and higher likelihood of positive cardiac tests. [63] In an observational study of patients from the general population with known cardiovascular disease, the 6-minute walk test (6MWT) was shown to be predictive of death and MACE, with predictive cut offs of 320m for death and 392m for MACE, with a sensitivity of 76% and specificity of 53%.  Each 50 meter increase in distance walked was associated with a lower hazard ratio of MACE. [64] A further observational study in kidney transplant waitlisted patients nearing the top of the list evaluated sit to stand in 60 seconds (STS60) and 6MWT in patients who were likely to receive a kidney transplant within the near future. [60] The median 6MWT distance travelled for the group was 393m (corresponding to 2.9 METS). The lowest tertile of patients achieved between 0 and 329m at assessment but just over half had died or been removed from the waiting list after 2 years.  The median distance covered was 305m in patients who died, 244m for patients removed from the wait list and 419m for transplant recipients.  Although measuring gait speed may provide a simple, low-cost method for identifying patients who require closer cardiac assessment, further corroborating studies are required to confirm this finding.  If confirmed, discussing with patients that physical activity correlates with outcomes may help encourage or motivate behaviour change.  Studies examining whether prehabilitation programmes are feasible pre-transplantation are ongoing (e.g.https://www.kidneyresearchuk.org/2024/01/29/can-prehabilitation-benefit-kidney-patients-preparing-for-transplant/).

Duke Activity Status Index

The Duke Activity Status Index (DASI) score is a structured, 12-question, validated tool for preoperative assessment of functional capacity. [65] Patients with a DASI score below 34 may be at increased risk of postoperative cardiovascular complications, which is often used in general elective surgery [52] as recommended by the UK Centre for Perioperative Care.  However, this has not been validated explicitly in kidney transplantation.  The DASI score has been modified and shortened; the modified DASI (M-DASI) score consists of 5 questions.  DASI and M-DASI scores are moderately correlated with VO₂ max determined by cardiopulmonary exercise testing (CPET) and walk tests. [66] [67] Individuals whose scores fell below the lower threshold of 34 in general surgical settings have an increased odds of 30-day emergency department visits, 30-day mortality and one-year mortality, as well as longer hospital length of stay, compared with patients whose scores exceeded the threshold. [52] A single-centre study examining the DASI score in kidney transplant candidates found that the DASI was not predictive of delayed graft function, unplanned critical care admission, length-of-stay, 30-day hospital re-admission, 30-day severe postoperative or cardiovascular complication, all-cause mortality, or death-censored graft loss, acknowledging that the examined cohort had good baseline functional status and a high median DASI score. [68]

Physical Activity Scale for the Elderly

The Physical Activity Scale for the Elderly (PASE) is a brief 5-minute survey originally designed for people aged 65 and older. [69] In one three-centre study, a PASE was administered to patients (not all of whom were elderly) at the time of kidney transplant.  Patients in the highest tertile of activity had a hazard ratio for all-cause mortality of 0.45 compared to those in the lowest tertile.  [70] This finding has been replicated in similar studies. [71] [72] However, these studies recruited participants at the time of transplantation, rather than at transplant listing. The utility of the PASE score to identify patients who would benefit from cardiac testing or who should be excluded from transplantation was not specifically examined.

Frailty assessments

Frailty assessments are multi-dimensional, covering various aspects of a patient’s functional status, including cognitive abilities, physical function, nutritional health, and psychosocial factors.  Many frailty tools have been developed.  These assessments are increasingly utilised in general surgical pathways to identify patients at risk of poorer surgical outcomes. [73] Patients identified as at risk may be offered alternative treatment options, prehabilitation, and additional support from a geriatrician-led multidisciplinary team.  This has been shown to improve postoperative outcomes in several surgical disciplines but has not been specifically evaluated in transplantation.  A raised Rockwood Clinical Frailty score ≥4 (adjusted for age and gender and often used as a screening tool for frailty in the elderly) is associated with an increased risk of death and withdrawal from the transplant waiting list. [74] In a UK study, over a third of patients aged > 60 years on the transplant list were frail or vulnerable. [75]  The prevalence of frailty in transplant candidates varies by the frailty measure used [74], and there is currently no consensus on the most appropriate tool to use in renal populations, how often frailty assessments should be performed, and what level of frailty may preclude transplantation or necessitate intervention. [76]

Cardiology involvement in transplant assessment

Given the limited sensitivity and specificity of non-invasive cardiac investigations in identifying patients with significant underlying coronary artery disease, and uncertainties regarding what threshold necessitates further investigation or intervention, we suggest a link cardiologist with an interest in kidney disease/transplantation works alongside the transplant multidisciplinary team (MDT) to guide decision making, or the creation of a formal cardio-renal MDT.  The aim is to ensure consistent, standardised practice, processes, and pathways.  Given that current tests rarely identify patients who should be subjected to revascularisation, tests should not be requested by ‘default’ and instead be used in specific clinical scenarios in liaison with cardiology.

Patients who undergo non-invasive cardiac tests demonstrating a low burden of ischaemia should have optimal medical management of CAD (see medical therapy chapter) and discussion with a link cardiologist or at a joint cardiology/renal transplant MDT.  Coronary angiography may not be required in this setting.  Patients with a high burden of ischaemia should be discussed at MDT with respect to further evaluation and consideration of coronary artery angiography.  Wherever possible, to aid communication, reduce unnecessary referrals, and speed the patient journey, units should have either a link cardiologist with an interest in kidney and familiarity with the relevant literature and guidelines, or a formal cardiac/transplant MDT.

Risk stratification

Risk stratification should initially be based on the presence or absence of cardiac disease symptoms in potential recipients.  Most studies have attempted to identify higher risk kidney transplant candidates using ‘conventional’ risk factors for CVD such as age, smoking history, dyslipidaemia, hypertension, diabetes mellitus and duration of dialysis.  Whilst some of these risk factors are potentially modifiable to improve long-term CVD outcomes for individual patients, they do not sufficiently discriminate between patients whose post-transplant prognosis precludes transplantation.  Therefore, using these ‘conventional’ risk factors to stratify potential recipients into a specific arm of the investigation pathway is not prognostically helpful.

Given that functional assessments and risk prediction tools can be performed with relative ease and speed in the outpatient clinic, we suggest that an initial risk assessment be conducted using these methods.  For patients with poor exercise tolerance (a suggestion being a DASI score of under 15 or a 6 minute walk distance of under 330m, which equates to highest cardiac intervention and event rate in observational studies [60] [64]) who are otherwise suitable for transplantation, transplant teams should consider non-invasive cardiac investigations ideally with liaison with their local link cardiologist regarding who should undergo further non-invasive cardiac investigations.  Patients with abnormalities on these investigations should be discussed with cardiology to guide medical optimisation and identify the select group of patients who may benefit from coronary intervention (see coronary revascularisation chapter).

Assessment of transplant risk is not based solely on MACE risk; a holistic consideration of other patient, organ, and immunological factors is needed.  We were unable to set a threshold for cardiac disease at which kidney transplantation is contraindicated, and there is a paucity of literature on this topic.  Furthermore, the individual patient’s understanding and acceptance of the risks associated with kidney transplantation should be considered. Figure 1 shows a suggested flow diagram for cardiovascular assessment of a potential kidney transplant candidate.

Patient perspective

This guidance was developed in collaboration with patient advocates who have personal experience with transplantation.  Patients appreciate the importance of rigorous assessment of their fitness for transplantation to confirm that the benefits outweigh the risks for the individual.  However, patients report a wide variation between transplant unit assessment protocols and delays in accessing the tests involved. [78] Pathways to transplant listing should be streamlined to eliminate unwarranted variation in assessment and reduce the burden of testing and unnecessary hospital appointments. The aim should be a personalised medicine approach to pre-transplant assessment that maintains safety while avoiding unnecessary testing and delays and ensuring equity for patients.