Portal de Periódicos da CAPES

Invasive Management of Coronary Artery Disease in Advanced Renal Disease

2021; Elsevier BV; Volume: 6; Issue: 6 Linguagem: Inglês

10.1016/j.ekir.2021.02.041

2468-0249

Keyvan Karimi Galougahi, Steven J. Chadban, Roxana Mehran, Sripal Bangalore, Glenn M. Chertow, Ziad A. Ali,

Renal and Vascular Pathologies

Coronary artery disease (CAD) is highly prevalent in chronic kidney disease (CKD). CKD modifies the effects of traditional risk factors on atherosclerosis, with CKD-specific mechanisms, such as inflammation and altered mineral metabolism, playing a dominant pathophysiological role as kidney function declines. Traditional risk models and cardiovascular screening tests perform relatively poorly in the CKD population, and medical treatments including lipid-lowering therapies have reduced efficacy. Clinical presentation of cardiac ischemia in CKD is atypical, whereas invasive therapies are associated with higher rates of complications than in with patients with normal or near normal kidney function. The main focus of the present review is on the invasive approach to management of CAD in late-stage CKD, with an in-depth discussion of the findings of the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA)-CKD trial, and their implications for therapeutic approach and future research in this area. We also briefly discuss the existing evidence in the epidemiology, pathogenesis, diagnosis, and medical management of CAD in late-stage CKD, end-stage kidney disease (ESKD), and kidney transplant recipients. We enumerate the evidence gap left by the frequent exclusion of patients with CKD from randomized controlled trials and highlight the priority areas for future research in the CKD population. Coronary artery disease (CAD) is highly prevalent in chronic kidney disease (CKD). CKD modifies the effects of traditional risk factors on atherosclerosis, with CKD-specific mechanisms, such as inflammation and altered mineral metabolism, playing a dominant pathophysiological role as kidney function declines. Traditional risk models and cardiovascular screening tests perform relatively poorly in the CKD population, and medical treatments including lipid-lowering therapies have reduced efficacy. Clinical presentation of cardiac ischemia in CKD is atypical, whereas invasive therapies are associated with higher rates of complications than in with patients with normal or near normal kidney function. The main focus of the present review is on the invasive approach to management of CAD in late-stage CKD, with an in-depth discussion of the findings of the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA)-CKD trial, and their implications for therapeutic approach and future research in this area. We also briefly discuss the existing evidence in the epidemiology, pathogenesis, diagnosis, and medical management of CAD in late-stage CKD, end-stage kidney disease (ESKD), and kidney transplant recipients. We enumerate the evidence gap left by the frequent exclusion of patients with CKD from randomized controlled trials and highlight the priority areas for future research in the CKD population. Cardiovascular disease is the leading cause of mortality in patients with CKD.1Sarnak M.J. Amann K. Bangalore S. et al.Chronic kidney disease and coronary artery disease: JACC state-of-the-art review.J Am Coll Cardiol. 2019; 74: 1823-1838Crossref PubMed Scopus (114) Google Scholar Patients with stages G3 to G4 CKD (estimated glomerular filtration rate [eGFR] 15–59 ml/min per 1.73 m2) have 2 to 3 times higher mortality compared with patients without CKD, with the probability of developing CAD increasing linearly as the glomerular filtration rate drops below 60 ml/min per 1.73 m2.2Manjunath G. Tighiouart H. Ibrahim H. et al.Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community.J Am Coll Cardiol. 2003; 41: 47-55Crossref PubMed Scopus (663) Google Scholar Patients maintained on dialysis incur the greatest risk of experiencing major adverse cardiovascular events,3Cozzolino M. Mangano M. Stucchi A. et al.Cardiovascular disease in dialysis patients.Nephrol Dial Transplant. 2018; 33: iii28-iii34Crossref PubMed Scopus (108) Google Scholar and although kidney transplantation is the best strategy to reduce this risk, cardiovascular disease remains the greatest cause of death for kidney transplant recipients.4Ying T. Shi B. Kelly P.J. et al.Death after kidney transplantation: an analysis by era and time post-transplant.J Am Soc Nephrol. 2020; 31: 2887-2899Crossref PubMed Scopus (7) Google Scholar Although atherosclerosis in early CKD is driven by standard risk factors compounded by albuminuria, nonstandard CKD-related risk factors (e.g., inflammation, oxidative stress, and metabolic bone disease, and vascular calcification) play a major role as glomerular filtration rate declines.3Cozzolino M. Mangano M. Stucchi A. et al.Cardiovascular disease in dialysis patients.Nephrol Dial Transplant. 2018; 33: iii28-iii34Crossref PubMed Scopus (108) Google Scholar,1Sarnak M.J. Amann K. Bangalore S. et al.Chronic kidney disease and coronary artery disease: JACC state-of-the-art review.J Am Coll Cardiol. 2019; 74: 1823-1838Crossref PubMed Scopus (114) Google Scholar,3Cozzolino M. Mangano M. Stucchi A. et al.Cardiovascular disease in dialysis patients.Nephrol Dial Transplant. 2018; 33: iii28-iii34Crossref PubMed Scopus (108) Google Scholar,5Fox C.S. Matsushita K. Woodward M. et al.Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis.Lancet. 2012; 380: 1662-1673Abstract Full Text Full Text PDF PubMed Scopus (594) Google Scholar,6Mahmoodi B.K. Matsushita K. Woodward M. et al.Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis.Lancet. 2012; 380: 1649-1661Abstract Full Text Full Text PDF PubMed Scopus (290) Google Scholar Adding to the complexity, the clinical presentation of cardiac ischemia in the CKD population is often atypical. Compared with approximately 70% of patients with normal or near normal kidney function, only 40% of patients with stages G3 to G5 CKD presenting with myocardial infarction (MI) have typical angina symptoms.7Sosnov J. Lessard D. Goldberg R.J. et al.Differential symptoms of acute myocardial infarction in patients with kidney disease: a community-wide perspective.Am J Kidney Dis. 2006; 47: 378-384Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar The atypical presentation of cardiac ischemia in patients with CKD thus warrants special effort to identify anginal equivalent symptoms, such as dyspnea or fatigue.1Sarnak M.J. Amann K. Bangalore S. et al.Chronic kidney disease and coronary artery disease: JACC state-of-the-art review.J Am Coll Cardiol. 2019; 74: 1823-1838Crossref PubMed Scopus (114) Google Scholar Diminished exercise tolerance, especially in patients with ESKD, may further limit presentation of classical angina. Indeed, patients with CKD are more likely to have MI as an initial manifestation of CAD,8Go A.S. Bansal N. Chandra M. et al.Chronic kidney disease and risk for presenting with acute myocardial infarction versus stable exertional angina in adults with coronary heart disease.J Am Coll Cardiol. 2011; 58: 1600-1607Crossref PubMed Scopus (38) Google Scholar and most present with non–ST-segment elevation MI (STEMI).9Shroff G.R. Li S. Herzog C.A. Trends in discharge claims for acute myocardial infarction among patients on dialysis.J Am Soc Nephrol. 2017; 28: 1379-1383Crossref PubMed Scopus (6) Google Scholar The higher frequency of presentation with non-STEMI compared with STEMI in patients with CKD may reflect left ventricular hypertrophy and subendocardial ischemia, the burden of atherosclerosis and degree of calcification, and a lower likelihood of ruptured fibrous cap as opposed to plaque erosion as the substrate for acute coronary syndromes.1Sarnak M.J. Amann K. Bangalore S. et al.Chronic kidney disease and coronary artery disease: JACC state-of-the-art review.J Am Coll Cardiol. 2019; 74: 1823-1838Crossref PubMed Scopus (114) Google Scholar In this review, we provide an overview of cardiovascular risk stratification and diagnostic approach to screening for CAD in late-stage CKD and in candidates for kidney transplantation. We discuss the conservative treatment with optimal medical therapy (OMT) alone or OMT in combination with invasive management, including cardiac catheterization using ultralow contrast volumes and zero-contrast percutaneous coronary intervention (PCI) to minimize the risk of contrast-induced nephropathy (CIN). We discuss the findings of the ISCHEMIA-CKD trial and make recommendations for future research in studying invasive versus conservative approach for management of CAD in advanced CKD. Predictive models in the general population (e.g., Framingham equation) have poor discrimination (i.e., the ability to separate those who experience a cardiac event from those who do not) in CKD.10Goff Jr., D.C. Lloyd-Jones D.M. Bennett G. et al.2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.Circulation. 2014; 129: S49-S73Crossref PubMed Scopus (1839) Google Scholar Predicted risks based on these models systematically fall below the actual observed risk.11Weiner D.E. Tighiouart H. Elsayed E.F. et al.The Framingham predictive instrument in chronic kidney disease.J Am Coll Cardiol. 2007; 50: 217-224Crossref PubMed Scopus (214) Google Scholar This systemic underestimation of cardiovascular risk is nonuniform and is driven by events competing with death, together with significantly higher cardiac event rates in CKD; thus, refitting the equations and assigning different weighted coefficients to traditional risk factors do not adequately improve risk stratification in CKD.11Weiner D.E. Tighiouart H. Elsayed E.F. et al.The Framingham predictive instrument in chronic kidney disease.J Am Coll Cardiol. 2007; 50: 217-224Crossref PubMed Scopus (214) Google Scholar Although the addition of eGFR and albuminuria can improve calibration (i.e., the measure of how closely predicted outcomes agree with actual outcomes) and risk discrimination of the predictive models,12Matsushita K. Coresh J. Sang Y. et al.Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data.Lancet Diabetes Endocrinol. 2015; 3: 514-525Abstract Full Text Full Text PDF PubMed Scopus (324) Google Scholar current clinical guidelines do not formally incorporate these readily available kidney-specific variables.13Stone N.J. Robinson J.G. Lichtenstein A.H. et al.2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.J Am Coll Cardiol. 2014; 63: 2889-2934Crossref PubMed Scopus (2940) Google Scholar Addition of biomarkers (e.g., vascular calcification, troponin I or T, C-reactive protein) may improve performance of the risk prediction models in early stage CKD; nonetheless, these risk assessment methods function poorly in ESKD.14Anker S.D. Gillespie I.A. Eckardt K.U. et al.Development and validation of cardiovascular risk scores for haemodialysis patients.Int J Cardiol. 2016; 216: 68-77Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar Dialysis modifies the effects of standard risk factors, although the increased rates of heart failure and sudden death in the dialysis population are not captured by the standard risk methods.1Sarnak M.J. Amann K. Bangalore S. et al.Chronic kidney disease and coronary artery disease: JACC state-of-the-art review.J Am Coll Cardiol. 2019; 74: 1823-1838Crossref PubMed Scopus (114) Google Scholar Thus, new cardiovascular risk models need to be developed and validated in ESKD. Finally, the Framingham equation underestimates cardiovascular risk in kidney transplant recipients, and modified equations have not been adequately validated in this population.15Kasiske B.L. Chakkera H.A. Roel J. Explained and unexplained ischemic heart disease risk after renal transplantation.J Am Soc Nephrol. 2000; 11: 1735-1743Crossref PubMed Google Scholar Regular screening for CAD in asymptomatic patients with CKD is not recommended because there is no evidence supporting efficacy of coronary revascularization in reducing death or MI in this group of patients.16Young L.H. Wackers F.J. Chyun D.A. et al.Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial.JAMA. 2009; 301: 1547-1555Crossref PubMed Scopus (606) Google Scholar In contrast, screening for CAD in symptomatic and asymptomatic, high-risk kidney transplant candidates is currently recommended but remains controversial. Although evidence from randomized controlled trials on the impact of this approach on clinical outcomes is lacking,17Lentine K.L. Costa S.P. Weir M.R. et al.Cardiac disease evaluation and management among kidney and liver transplantation candidates: a scientific statement from the American Heart Association and the American College of Cardiology Foundation.J Am Coll Cardiol. 2012; 60: 434-480Crossref PubMed Scopus (228) Google Scholar the perioperative safety of kidney transplantation in patients with high risk for CAD remains a rationale for screening and revascularization. In the non-CKD population, functional stress testing and noninvasive coronary imaging are used to assess ischemia and atherosclerosis burden, to evaluate prognosis, and to risk-stratify patients for coronary revascularization and optimization of medical therapy. Diagnosing CAD in patients with CKD may be more challenging. Exercise testing and pharmacologic perfusion imaging have reduced accuracy for detecting CAD in CKD, with higher rates of false-negative and false-positive tests.9Shroff G.R. Li S. Herzog C.A. Trends in discharge claims for acute myocardial infarction among patients on dialysis.J Am Soc Nephrol. 2017; 28: 1379-1383Crossref PubMed Scopus (6) Google Scholar,18Winther S. Svensson M. Jorgensen H.S. et al.Diagnostic performance of coronary CT angiography and myocardial perfusion imaging in kidney transplantation candidates.JACC Cardiovasc Imaging. 2015; 8: 553-562Crossref PubMed Scopus (61) Google Scholar Exercise testing is limited by frequently low functional capacity in patients with CKD19Patel R.K. Mark P.B. Johnston N. et al.Prognostic value of cardiovascular screening in potential renal transplant recipients: a single-center prospective observational study.Am J Transplant. 2008; 8: 1673-1683Crossref PubMed Scopus (96) Google Scholar and baseline electrocardiographic abnormalities (e.g., left ventricular hypertrophy) that may affect interpretation of ST-segment changes. In addition, most of the current evidence is from studies in transplant candidates. Patients with ESKD, who are deemed unsuitable candidates for kidney transplantation, typically have lower functional capacity, more comorbidities, and higher burden of CAD; the prognostic value of cardiovascular risk stratification in this larger population of patients with ESKD is unknown.1Sarnak M.J. Amann K. Bangalore S. et al.Chronic kidney disease and coronary artery disease: JACC state-of-the-art review.J Am Coll Cardiol. 2019; 74: 1823-1838Crossref PubMed Scopus (114) Google Scholar Given the high pretest probability of CAD and the moderate sensitivity of noninvasive tests, these tests may have a low negative predictive value, that is, they may not exclude functionally significant or anatomically high-risk disease. Coronary artery calcium score or computed tomography angiography (CTA) has some potential advantages over functional imaging in the CKD population. In a comparison of coronary artery calcium score, CTA, exercise, or pharmacologic stress single-photon emission computed tomography in which stenosis >50% was detected by quantitative coronary angiography in 138 kidney transplant candidates, coronary artery calcium score and single-photon emission computed tomography had modest specificity (67% and 53%, respectively) and sensitivity (77% and 82%, respectively), whereas CTA had a high sensitivity (93%) but low specificity (63%).18Winther S. Svensson M. Jorgensen H.S. et al.Diagnostic performance of coronary CT angiography and myocardial perfusion imaging in kidney transplantation candidates.JACC Cardiovasc Imaging. 2015; 8: 553-562Crossref PubMed Scopus (61) Google Scholar Risk of acute kidney injury (AKI) should be considered with CTA, particularly in late-stage CKD,20Winther S. Svensson M. Jørgensen H.S. et al.Repeated contrast administration is associated with low risk of postcontrast acute kidney injury and long-term complications in patients with severe chronic kidney disease.Am J Transplant. 2016; 16: 897-907Crossref PubMed Scopus (12) Google Scholar including the diminished use of CTA in the CKD population with accelerated coronary calcification (predominantly medial vascular calcification), which can confound the assessment of occlusive atherosclerotic CAD.21Kruk M. Noll D. Achenbach S. et al.Impact of coronary artery calcium characteristics on accuracy of CT angiography.JACC Cardiovasc Imaging. 2014; 7: 49-58Crossref PubMed Scopus (52) Google Scholar Assessment of myocardial perfusion with positron emission tomography (PET) using various tracers allows for quantification of rest and stress myocardial blood flow to compute coronary flow reserve (CFR = stress myocardial blood flow/rest myocardial blood flow) in addition to semiquantitative analysis of ischemia and scar.22Murthy V.L. Naya M. Foster C.R. et al.Coronary vascular dysfunction and prognosis in patients with chronic kidney disease.JACC Cardiovasc Imaging. 2012; 5: 1025-1034Crossref PubMed Scopus (87) Google Scholar In the non-CKD population, sensitivity of flurpiridaz PET for detection of CAD with ≥50% stenosis on angiography was higher than single-photon emission computed tomography (71.9% vs. 53.7%), with improved image quality, diagnostic certainty, and lower radiation exposure23Maddahi J. Lazewatsky J. Udelson J.E. et al.Phase-III clinical trial of fluorine-18 Flurpiridaz positron emission tomography for evaluation of coronary artery disease.J Am Coll Cardiol. 2020; 76: 391-401Crossref PubMed Scopus (15) Google Scholar; nonetheless, this comparison has not been performed in the CKD population. Compared with patients with preserved kidney function, PET-CFR is lower in early stage CKD, without further decrement in stage 5 or dialysis-dependent ESKD.24Charytan D.M. Skali H. Shah N.R. et al.Coronary flow reserve is predictive of the risk of cardiovascular death regardless of chronic kidney disease stage.Kidney Int. 2018; 93: 501-509Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar In late-stage CKD, PET-CFR below the median value of 1.5 was associated with a 2.1-fold increase in the adjusted risk of cardiac death.22Murthy V.L. Naya M. Foster C.R. et al.Coronary vascular dysfunction and prognosis in patients with chronic kidney disease.JACC Cardiovasc Imaging. 2012; 5: 1025-1034Crossref PubMed Scopus (87) Google Scholar Incorporation of PET-CFR in cardiac death risk assessment models resulted in a net reclassification improvement, with 8% upward and 12% downward reclassification of patients into more accurate risk categories.22Murthy V.L. Naya M. Foster C.R. et al.Coronary vascular dysfunction and prognosis in patients with chronic kidney disease.JACC Cardiovasc Imaging. 2012; 5: 1025-1034Crossref PubMed Scopus (87) Google Scholar PET-CFR was also independently associated with all-cause and cardiovascular mortality in ESKD, and addition of PET-CFR resulted in risk reclassification in 27% of patients.25Shah N.R. Charytan D.M. Murthy V.L. et al.Prognostic value of coronary flow reserve in patients with dialysis-dependent ESRD.J Am Soc Nephrol. 2016; 27: 1823-1829Crossref PubMed Scopus (42) Google Scholar Cardiac troponins are frequently elevated in advanced CKD. The mechanisms for elevated troponin levels are not fully understood; nevertheless, troponin T and I elevations are associated with increased all-cause and cardiovascular mortality in CKD.26Eggers K.M. Lindahl B. Carrero J.J. et al.Cardiac troponins and their prognostic importance in patients with suspected acute coronary syndrome and renal dysfunction.Clin Chem. 2017; 63: 1409-1417Crossref PubMed Scopus (8) Google Scholar,27Gunsolus I. Sandoval Y. Smith S.W. et al.Renal dysfunction influences the diagnostic and prognostic performance of high-sensitivity cardiac troponin I.J Am Soc Nephrol. 2018; 29: 636-643Crossref PubMed Scopus (29) Google Scholar Severe CAD is more common among patients with ESKD and elevated troponin T.28deFilippi C. Wasserman S. Rosanio S. et al.Cardiac troponin T and C-reactive protein for predicting prognosis, coronary atherosclerosis, and cardiomyopathy in patients undergoing long-term hemodialysis.JAMA. 2003; 290: 353-359Crossref PubMed Scopus (335) Google Scholar Elevation may also indicate subclinical myocardial damage, for example, transient myocardial stunning during hemodialysis.29Breidthardt T. Burton J.O. Odudu A. et al.Troponin T for the detection of dialysis-induced myocardial stunning in hemodialysis patients.Clin J Am Soc Nephrol. 2012; 7: 1285-1292Crossref PubMed Scopus (39) Google Scholar Although the sensitivity of high-sensitivity troponin I in the diagnosis of MI is not modified by kidney function, its specificity progressively decreases from 93%–95% in patients with preserved renal function to 40%–41% in ESKD.27Gunsolus I. Sandoval Y. Smith S.W. et al.Renal dysfunction influences the diagnostic and prognostic performance of high-sensitivity cardiac troponin I.J Am Soc Nephrol. 2018; 29: 636-643Crossref PubMed Scopus (29) Google Scholar Dynamic changes in troponin levels compared with the baseline levels may increase the specificity for diagnosing MI in ESKD.1Sarnak M.J. Amann K. Bangalore S. et al.Chronic kidney disease and coronary artery disease: JACC state-of-the-art review.J Am Coll Cardiol. 2019; 74: 1823-1838Crossref PubMed Scopus (114) Google Scholar Deceased donor kidney transplantation is an elective surgery performed under emergent situations.1Sarnak M.J. Amann K. Bangalore S. et al.Chronic kidney disease and coronary artery disease: JACC state-of-the-art review.J Am Coll Cardiol. 2019; 74: 1823-1838Crossref PubMed Scopus (114) Google Scholar Screening of transplant candidates for CAD is performed to guide selection of appropriate candidates, inform transplant options, maintain eligibility during wait-listing, minimize and inform the risk of peritransplant events, and optimize post-transplant survival. Cardiovascular events after transplantation may compromise long-term survival and allograft function.1Sarnak M.J. Amann K. Bangalore S. et al.Chronic kidney disease and coronary artery disease: JACC state-of-the-art review.J Am Coll Cardiol. 2019; 74: 1823-1838Crossref PubMed Scopus (114) Google Scholar Nonetheless, whether treatment guided by screening prevents early post-transplant cardiovascular events and improves long-term outcomes is not known. Patients with signs or symptoms suggestive of CAD should be tested.30Bhatti N.K. Karimi Galougahi K. Paz Y. et al.Diagnosis and management of cardiovascular disease in advanced and end-stage renal disease.J Am Heart Assoc. 2016; 5e003648Crossref PubMed Scopus (36) Google Scholar Among asymptomatic patients, screening for subclinical CAD is recommended by the US guidelines and has been integrated in clinical transplant practice despite limited evidence that screening reduces the risk of CAD events.17Lentine K.L. Costa S.P. Weir M.R. et al.Cardiac disease evaluation and management among kidney and liver transplantation candidates: a scientific statement from the American Heart Association and the American College of Cardiology Foundation.J Am Coll Cardiol. 2012; 60: 434-480Crossref PubMed Scopus (228) Google Scholar Transplant guidelines recommend screening based on the presence of cardiovascular risk factors, using noninvasive screening tests at the time of activation to the wait-list and periodically during wait-listing, with the objective of identifying patients with subclinical CAD who are candidates for revascularization or medical therapy.30Bhatti N.K. Karimi Galougahi K. Paz Y. et al.Diagnosis and management of cardiovascular disease in advanced and end-stage renal disease.J Am Heart Assoc. 2016; 5e003648Crossref PubMed Scopus (36) Google Scholar It is possible that screening may, paradoxically, cause harm by unnecessarily subjecting patients to invasive procedures and delaying/excluding them from transplantation.31Friedman S.E. Palac R.T. Zlotnick D.M. et al.A call to action: variability in guidelines for cardiac evaluation before renal transplantation.Clin J Am Soc Nephrol. 2011; 6: 1185-1191Crossref PubMed Scopus (41) Google Scholar There are several issues regarding the current screening paradigm. First, cardiovascular mortality in CKD may be secondary to arrhythmia rather than MI. Second, noninvasive screening tests lack sensitivity and specificity to identify asymptomatic patients with clinically significant CAD warranting revascularization.32Wang L.W. Fahim M.A. Hayen A. et al.Cardiac testing for coronary artery disease in potential kidney transplant recipients.Cochrane Database Syst Rev. 2011; 2011: CD008691Google Scholar Last, evidence that revascularization would improve outcomes is lacking.17Lentine K.L. Costa S.P. Weir M.R. et al.Cardiac disease evaluation and management among kidney and liver transplantation candidates: a scientific statement from the American Heart Association and the American College of Cardiology Foundation.J Am Coll Cardiol. 2012; 60: 434-480Crossref PubMed Scopus (228) Google Scholar The American Heart Association/American College of Cardiology scientific statement recommends that initial screening before wait-list activation "may be considered in transplant candidates with no active disease but with multiple risk factors for CAD" (class IIB, level of evidence: C).17Lentine K.L. Costa S.P. Weir M.R. et al.Cardiac disease evaluation and management among kidney and liver transplantation candidates: a scientific statement from the American Heart Association and the American College of Cardiology Foundation.J Am Coll Cardiol. 2012; 60: 434-480Crossref PubMed Scopus (228) Google Scholar As described earlier, noninvasive testing for CAD has modest sensitivity and specificity in ESKD. Current guidelines recommend exercise or pharmacologic stress echocardiogram or nuclear scintigraphy. There are limited data on the role of CTA in dialysis patients undergoing screening before renal transplantation.33Mao J. Karthikeyan V. Poopat C. et al.Coronary computed tomography angiography in dialysis patients undergoing pre-renal transplantation cardiac risk stratification.Cardiol J. 2010; 17: 349-361PubMed Google Scholar Given the absence of contemporary data to support revascularization of screen-detected CAD before transplantation to improve transplant outcomes, the 2020 Kidney Disease: Improving Global Outcomes guidelines do not recommend revascularization in asymptomatic candidates.34Chadban S.J. Ahn C. Axelrod D.A. et al.KDIGO clinical practice guideline on the evaluation and management of candidates for kidney transplantation.Transplantation. 2020; 104: S11-S103Crossref PubMed Scopus (58) Google Scholar The risks of perioperative delayed graft function and death are lower among living compared with deceased donor transplantation patients. Nonetheless, the consequences of adverse perioperative events are more troublesome in living donor than in the deceased donor recipients—losing a living donor kidney may have substantial emotional impact.1Sarnak M.J. Amann K. Bangalore S. et al.Chronic kidney disease and coronary artery disease: JACC state-of-the-art review.J Am Coll Cardiol. 2019; 74: 1823-1838Crossref PubMed Scopus (114) Google Scholar In the US health care system, it may lead to increased regulatory scrutiny and penalties for transplant programs. Consequently, there may be an even lower threshold to screen and intervene in asymptomatic living donor candidates despite the relative absence of evidence that this approach is beneficial.1Sarnak M.J. Amann K. Bangalore S. et al.Chronic kidney disease and coronary artery disease: JACC state-of-the-art review.J Am Coll Cardiol. 2019; 74: 1823-1838Crossref PubMed Scopus (114) Google Scholar Given these differences from deceased donor transplantation, development of an evidence-based screening strategy for living donor candidates is warranted. In addition to screening before acceptance into the transplant waiting list, the current standard of care involves screening asymptomatic patients at variable intervals after wait-listing until transplantation (class IIB, level of evidence: C).17Lentine K.L. Costa S.P. Weir M.R. et al.Cardiac disease evaluation and management among kidney and liver transplantation candidates: a scientific statement from the American Heart Association and the American College of Cardiology Foundation.J Am Coll Cardiol. 2012; 60: 434-480Crossref PubMed Scopus (228) Google Scholar Some transplant programs have adopted a strategy of deferred screening in which only patients who have accrued significant waiting time and are expected to receive a deceased donor offer in the near future are screened.1Sarnak M.J. Amann K. Bangalore S. et al.Chronic kidney disease and coronary artery disease: JACC state-of-the-art review.J Am Coll Cardiol. 2019; 74: 1823-1838Crossref PubMed Scopus (114) Google Scholar Until new evidence becomes available, the benefit of periodically screening asymptomatic patients during wait-listing remains uncertain. The Canadian-Australasian Randomised Trial of Screening Kidney Transplant Reci