How to Manage the Renal Patient with Coronary Heart Disease
Authors: Charles A. Herzog
Journal: Journal of the American Society of Nephrology (2003)

The management of ischemic heart disease in patients with chronic kidney disease (CKD) is a special challenge for clinicians. The recent heightened awareness of CKD as an important risk factor for cardiovascular death is a welcome development; the eventual outcome will be clinical trials targeting CKD patients for prevention and treatment of coronary heart disease and its devastating complications. The reader is urged to consult National Kidney Foundation (NKF) task forces dealing with cardiovascular disease in chronic renal failure (1,2) and, most recently, lipid management (3). At the present time, however, clinicians are often faced with a nettlesome dilemma in their approach to renal patients with ischemic heart disease; most of the evidence-based practice guidelines are based on clinical trials performed in patients without CKD. Patients with renal disease have typically been excluded from major cardiovascular treatment trials in the past; although there is no shortage of recent reviews on cardiovascular disease in renal disease (4–10), there is most certainly a paucity of good clinical trial data in CKD patients. The application of imperfect data to clinical practice, however, is nothing new for clinicians, as this is common in medical practice. It is not my intention to offer a general review on cardiovascular disease and renal disease, but rather to present my (admittedly idiosyncratic) approach to clinical management of coronary heart disease in renal patients distilled partly from the literature and personal experience. This paper will focus on cardiac disease in dialysis patients, but I will also attempt to frame special cardiac management issues pertaining to nondialysis CKD patients. Background Epidemiology and the Burden of Cardiovascular Disease in ESRD Patients Patients receiving renal replacement therapy on dialysis are at extraordinarily high risk for death. The death rate for all US dialysis patients in 1998–2000 was 236/1000 patient-years (11). Cardiac disease is the major cause of death in dialysis patients, accounting for about 45% of all-cause mortality (12). Approximately 20% of cardiac deaths are attributed to acute myocardial infarction (AMI) (12). The burden of coronary heart disease in end-stage renal disease (ESRD) patients is projected to increase, as the greatest increase in treated ESRD has occurred in patients with the highest risk for cardiovascular disease, older patients and those with diabetic nephropathy. There were an estimated 315,000 US dialysis patients in 2002 (11), with a projected number of 520,000 US dialysis patients in 2010 (12). The number of patients with non–dialysis-dependent renal failure is considerably larger. In 1988–1994, there were an estimated 10.9 million US patients having chronic renal insufficiency with serum creatinine > 1.5 mg/dl (13). These projections raise an interesting "paradox of the missing dialysis patients"— why is the "feeder" population of CKD more than 30 times larger than the dialysis population? It appears that the risk of death for (nondialysis) CKD patients is considerably greater than developing ESRD (11). A plausible explanation is that excess cardiovascular death (including coronary heart disease) in the CKD population prevents most CKD patients from developing ESRD; even "mild" renal insufficiency is associated with increased cardiovascular mortality (14,15). Logically, the greatest potential survival benefit from cardiac intervention in patients with renal disease would be derived from targeting patients for CHD prevention and treatment before the development of severe CKD. Chronic renal failure is a condition characterized by generalized vasculopathy (16). A variety of risk factors (many of them important in CKD patients before the development of ESRD) contributing to accelerated cardiovascular morbidity and mortality in renal patients include hypertension, dyslipidemia, hyperglycemia, smoking, physical inactivity, enhanced thrombogenicity, hyperparathyroidism, hyperhomocystinemia, increased sympathetic tone (including sleep apnea), and elevated levels of ADMA (asymmetric dimethyl arginine). The development of left ventricular hypertrophy may be promoted by anemia and vascular noncompliance. Aortic stiffness (assessed by aortic pulse wave velocity) is an independent predictor of cardiovascular and all-cause death in dialysis patients (17). Premature coronary artery calcification has been detected in young dialysis patients, and the metabolic milieu of ESRD, including elevated calcium-phosphate product (18), and the synergistic effect of hyperparathyroidism, and inflammation (as reflected by levels of C-reactive protein) (19) may be implicated. Vascular endothelial dysfunction likely contributes to the expression of atherosclerotic disease, and even a single hemodialysis run may adversely affect endothelial function (20). Hyperglycemia may markedly reduce coronary vasodilator function (21) (by promoting the formation of advanced glycation end-products, which oppose nitric oxide-mediated endothelial-dependent relaxation) (22). The composition of coronary plaques in patients with ESRD may be qualitatively different, with increased media thickness and marked calcification of the affected coronary arteries (23,24). The pathophysiologic significance of coronary artery calcification in ESRD patients, therefore, may be different from the nonrenal population. It is nearly impossible to accurately apportion the absolute contribution of "obstructive" coronary artery disease to cardiovascular morbidity and mortality in ESRD patients. This may strike some readers as pedantic, but it does have implications for the potential magnitude of therapeutic benefit that can be derived from coronary revascularization. Sudden cardiac death may be implicated in 60% of all cardiac deaths in dialysis patients. In the United States Renal Data System (USRDS) database, "cardiac arrest, cause unknown" accounts for 47% of all cardiac deaths, and another 13% are attributed to arrhythmia (25). Besides obstructive coronary artery disease (CAD), factors contributing to the peculiar vulnerability of ESRD patients to sudden death include left ventricular hypertrophy, electrolyte shifts in hemodialysis patients, and abnormalities in myocardial ultrastructure and function, including endothelial function, interstitial fibrosis, decreased perfusion reserve, and diminished ischemia tolerance (26–29). The nonphysiologic nature of conventional hemodialysis schedules (usually administered thrice weekly in the United States on Monday, Wednesday, Friday or Tuesday, Thursday, Saturday) may also contribute to increased cardiac death; this hypothesis is based on a study by Bleyer et al. (30), who found that significantly higher cardiac mortality occurs on Mondays (and to a lesser extent, Tuesday, the other dialysis day after the long interdialytic weekend). It is plausible that long-duration daily hemodialysis might lead to improved survival in ESRD patients, particularly if maintenance of "physiologic loading conditions" is accompanied by the amelioration of left ventricular hypertrophy and avoidance of significant electrolyte abnormalities (interdialytic hyperkalemia and intradialytic hypokalemia). Acute Myocardial Infarction Acute myocardial infarction in dialysis patients is a catastrophic event associated with dismal long-term survival (31–33). We have previously reported a 1-yr 59% mortality and 2-yr 73% mortality in 34,189 dialysis patients hospitalized with AMI in the US from 1977 to 1995 (31) (Figure 1). Even more striking is the poor outcome of patients treated in the "era of reperfusion," with 1-yr and 2-yr mortalities of 62% and 74% in 1990–95, and 2-yr mortality of 78% in 1991–97 (34). Renal transplant recipients fare better, with a 2-yr mortality of 34% after hospitalization for AMI in 1977–96 (35).Figure 1.: Estimated mortality of dialysis patients after acute myocardial infarction (MI). Reprinted with permission from Herzog CA, Ma JZ, Collins AJ: Poor long-term survival after acute myocardial infarction among patients on long-term dialysis. N Engl J Med 339: 799–805, 1998.We have speculated that the poor outcome of these patients may be due to a combination of underdiagnosis and undertreatment (i.e., therapeutic nihilism) (36) — "To the guy with a hammer, everything looks like a nail." If a dialysis patient arrives on a Monday morning in the outpatient dialysis unit 5 kg above dry weight and complaining of dyspnea and angina, what procedure is most likely to occur first: an electrocardiogram (ECG) or the scheduled dialysis run? Circulatory congestion attributable to the ingestion of pepperoni pizzas and myocardial ischemia due to AMI might cause the same symptoms, and a nephrologist could easily choose dialysis as the first procedure under these clinical circumstances, with potentially devastating results if the patient's primary problem is actually AMI and not pepperoni pizza. Ongoing preliminary work at the Cardiovascular Special Studies Center of USRDS and a recent publication by Berger et al. (36a) suggest both underrecognition of AMI due to "atypical clinical presentations" and undertreatment. Poor survival after AMI is a general phenomenon in patients with CKD, and it is not restricted to dialysis patients. There is an increasing gradient of mortality risk observed with more severe renal dysfunction in AMI (37–39). In-hospital mortality is correlated with renal function, and there is a strikingly greater risk of death in patients with estimated creatinine clearance (CrCl) < 60 ml/min. (Figure 2) One-year AMI mortality in elderly (≥65 yr) patients enrolled in the Cooperative Cardiovascular Project (CCP) in 1994–95 was 24% in patients with serum creatinine <1.5 mg/dl, 46% for Cr = 1.5 to 2.4 mg/dl, and 66% for Cr = 2.5 to 3.9 mg/dl (38). Similar findings were reported by Walsh et al. (40). In a recent pooled analysis from the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO II-b, GUSTO-III) studies, Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrillin Therapy (PURSUIT), and Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON-A) acute coronary syndrome trials, both ST-segment elevation and non-ST-segment elevation MI with CrCl < 70 ml/min were associated with increased 1-mo and 6-mo mortality (41).Figure 2.: In-hospital mortality as a function of creatinine (Cr) clearance (P < 0.001). Reprinted with permission from Wright RS, Reeder GS, Herzog CA, Albright RC, Williams BA, Dvorak DL, Miller WL, Murphy JG, Kopecky SL, Jaffe AS: Acute myocardial infarction and renal dysfunction: a high-risk combination. Ann Intern Med 137: 563–570, 2002.One astounding finding in patients with CKD and AMI is that the likelihood of receiving therapies proven to reduce mortality in clinical trials on AMI treatment is inversely related to the severity of renal failure (36a,37–39,42). This applies to the use of aspirin, β-blockers, and reperfusion therapy. In the study by Wright et al. (37), the use of angiotensin-converting enzyme (ACE) inhibitors at hospital discharge was also inversely related to the degree of renal impairment. Importantly, in these observational studies, the use of all these standard therapies were associated with decreased mortality. In the McCullough et al. study (42) from Henry Ford Hospital, the age-adjusted relative risk reduction of in-hospital mortality for patients receiving aspirin and β-blockers ranged from 64% to 80% across all renal function groups (compared with no treatment with either agent). In the Wright et al. study at the Mayo Clinic, the use of aspirin and β-blocker therapy at discharge and initial treatment with reperfusion therapy were independently associated with a 30% reduction in post-discharge deaths. In the Shlipak et al. study (38) of Medicare beneficiaries in the CCP database, aspirin was associated with a 48% to 60% range of reduction in 1-mo mortality across renal function categories, β-blockers were associated with a 38 to 42% reduction in 1-mo mortality, and ACE inhibitors were associated with a 48% to 59% reduction in 1-mo mortality. We have reported preliminary findings on the apparent under-utilization of thrombolytic therapy in dialysis patients. Using claims data from USRDS, we identified 33,277 dialysis patients hospitalized for AMI in 1991–97 who did not receive coronary reperfusion therapy and suffered a 2-yr mortality rate of 78%, compared with 176 patients receiving intravenous thrombolytic therapy with a 2-yr mortality rate of 60%. In a comorbidity-adjusted Cox model, thrombolytic therapy was associated with a 28% reduction in all-cause death risk (34). The poor outcome of CKD patients with AMI would appear to be partially attributable to therapeutic nihilism (and for dialysis patients, perhaps fueled by fear of potential complications such as hemorrhage and the unavailability of clinical trial outcome data due to the exclusion of ESRD patients from all AMI trials). For patients with AMI, no treatment is equivalent to bad treatment. The use of glycoprotein IIb/IIIa receptor antagonists as adjunctive therapy in acute coronary syndromes and percutaneous coronary intervention (PCI) in CKD is more controversial but supported by recent data. In the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial of tirofiban in acute coronary syndrome (ACS) (patients excluded for Cr ≥ 2.5 mg/dl), tirofiban was effective in reducing ischemic ACS complications, and there was no synergistic relationship between use of tirofiban and degree of renal impairment for the development of hemorrhagic complications (43). Using observational data from the Michigan Cardiovascular Outcomes and Reporting Program, Freeman et al. (44) reported an increase in major bleeding and reduced in-hospital mortality in patients with ACS and renal failure receiving glycoprotein (GP) IIb/IIIa antagonists. In the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial (eptifibatide), the beneficial effect of the agent and attributable hemorrhagic complications were not different in patients with CrCl < 60 ml/min (mean, 48 ml/min). Jeremias et al. (45) reported no increased risk of complications with abciximab in patients undergoing PCI with Cr ≥ 2.0 mg/dl (findings concordant with a recent publication by Best et al. [45a]). In contrast, Frilling et al. (46), using the Ludwigshafen IIb/IIIa-Antagonist Registry, reported a fivefold risk of any bleeding associated with abciximab in 44 patients with impaired renal function (Cr ≥ 1.3 mg/dl), but the absolute number of episodes was only 6.8%. There are a paucity of data on the use of glycoprotein IIb/IIIa antagonists in dialysis patients, although anecdotally, abciximab is probably the most widely used of these agents in dialysis patients undergoing PCI. Current US product labeling of available GP IIb/IIIa antagonists includes a reduced dose of eptifibatide in chronic renal failure (with no additional recommendation for Cr ≥ 4.0 mg/dl), 50% reduction in tirofiban dose in dialysis patients, and no dose adjustment for abciximab. It should be stressed that there are currently few published data on the safety and efficacy of these agents in dialysis patients. Prudence dictates careful clinical observation of all dialysis patients after PCI (including ready availability of blood products), regardless of the particular therapeutic strategy employed. Anticoagulation practice in dialysis patients with PCI and/or ACS will be limited by elimination kinetics of the drugs (including uncertainty in dialysis patients) and the ability to monitor therapy. During PCI, the monitoring of activated clotting time allows for dose-adjustment with unfractionated heparin. Low–molecular weight heparin has generally been avoided in ESRD patients, partly due to safety issues (with very prolonged half-life) and, until recently, inability to rapidly monitor therapeutic effect. One useful anticoagulant agent in ESRD patients undergoing PCI is bivalirudin (Angiomax), a direct thrombin inhibitor, which is predominantly renally excreted, and (FDA-approved) appropriate adjustments for all degrees of renal impairment, including dialysis-dependence, are provided by the manufacturer (47). Other untested adjunctive therapies for ACS in ESRD patients appear promising. The use of clopidogrel reduces the risk of recurrent cardiovascular events (with an increased risk of bleeding) in the "general population" (48). At my institution, we have generalized the results of the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial (48) and applied them to ESRD patients (a practice consistent with the application of other therapies not specifically tested in ESRD patients but proven in the general population). In the setting of PCI with coronary stenting, the combination of 81 to 325 mg/d aspirin (lifelong) and clopidogrel (30 d or longer if used for other indications) is standard therapy, including for ESRD patients. Patients with ESRD due to diabetic nephropathy have a 34% increased risk of death after AMI (compared with non-DM) (31). In diabetic patients with AMI, insulin glucose infusion reduces long-term mortality (49,50). It has been proposed that some of the cardioprotective benefit of insulin may derive from myocardial effects independent of metabolic modulation (51). Future trials in diabetic CKD patients would be appropriate. Tables 1 to 3 summarize our general approach to the management of AMI in dialysis patients. In chronic hemodialysis patients, the optimal timing for resumption of routine dialysis is controversial. In our own program, we have arbitrarily delayed routine dialysis in the first 24 h after AMI (unless forced by metabolic derangements), a practice supported by preliminary data from Kong et al. (52), who reported that 20% of 45 dialysis patients with AMI suffered unexpected ventricular fibrillation during hemodialysis, with five lethal outcomes.Table 1: Acute myocardial infarction (AMI) in dialysis patients: diagnostic pitfallsaTable 2: Treatment of AMI in dialysis patientsaTable 3: Pitfalls in the treatment of AMI in dialysis patientsMedical Management of Chronic CAD in Dialysis Patients Table 4 summarizes our general approach to the medical management of ischemic heart disease in dialysis patients. Most approaches to treatment represent generalization of established therapies in non-ESRD, with a few modifications. The maintenance of relative euvolemia is a key aspect of the management of these patients (53). Hemodynamic target dry weight may be a moving target in chronic dialysis patients (particularly diabetic patients), who may lose muscle mass over time—the same weight might denote inadequate fluid removal 2 yr later with declining lean body mass. In our practice, we rely on echocardiography for assessment of hemodynamic dry weight and occasionally elective right heart catheterization followed by right heart monitoring during dialysis/ultrafiltration to help determine true hemodynamic dry weight. Anemia may exacerbate angina; adherence to Dialysis Outcomes Quality Initiative (DOQI) anemia treatment guidelines is assumed in these patients. Hemodialysis can trigger angina, and alterations in dialysis prescription, including prolongation of treatment time to permit decreased ultrafiltration rate may be helpful in amelioration of dialysis-associated myocardial ischemia (54). Some nephrologists will sometimes omit anti-anginal therapy before dialysis if it is perceived that the agents are exacerbating unstable intradialytic hemodynamics, but this practice is more empiric than evidence-based. Inability to perform dialysis without hemodynamic instability or angina, however, should prompt further cardiac investigations for assessment of left ventricular (LV) function, valvular disease, and CAD. Obviously, inability to perform dialysis without untoward events constitutes failure of medical therapy and deserves further cardiac evaluation.Table 4: Medical management of chronic CAD in dialysis patientsThe treatment of dyslipidemia in chronic renal failure was the subject of a recent DOQI task force, and the reader is urged to consult this comprehensive document (3). Previous treatment trials in dialysis patients have essentially been large case series and pilot studies. Statin therapy (e.g. simvastatin in placebo-controlled randomized trial) is safe and efficacious for treatment of hypercholesteremia in dialysis patients (55,56). It is reasonable to treat dialysis patients (or for that matter CKD patients) as CHD-equivalent (like diabetes) and treat to a goal of LDL-cholesterol < 100 mg/dl. It is a bit more uncertain for the frequent occurrence in chronic hemodialysis patients of "low HDL-cholesterol, normal LDL-cholesterol, and increased triglycerides (the typical type 2 DM profile). In these patients, we will use statins for overt CHD, but it is less clear if they should be used for all dialysis patients. It is plausible that these high-risk patients might all benefit from statin therapy. Hopefully, the 4-D (Die Deutsche Diabetes Dialyze Studie) trial on the use of atorvastatin in type 2 diabetic patients will resolve this issue in dialysis patients. On the basis of current enrollment and event rates, preliminary data may be available in 2004. In my own practice, I sometimes employ combination therapy with statins (frequently atorvastatin) and sustained-release niacin (Niaspan) in patients with elevated LDL-cholesterol, decreased HDL-cholesterol, and increased triglycerides who do not respond adequately to monotherapy with a statin. Hepatic enzymes are monitored frequently in these patients on combination therapy. Combination therapy with ezetimibe, an inhibitor of intestinal brush border absorption of cholesterol, and statins is another approach to reducing LDL-cholesterol. The Study of Heart and Renal Protection (SHARP) trial, which began enrollment in June 2003 will test the efficacy of ezetemide and simvastatin for the reduction of cardiovascular events in patients with varying degrees of CKD, including ESRD. The cornerstone of medical therapy for CHD (and cardiomyopathy) might be β-blockers. Dialysis patients with dilated cardiomyopathy benefit from β-blocker therapy (57–59). The publication of a randomized, placebo-controlled trial of carvedilol in 114 Neapolitan dialysis patients with a dilated cardiomyopathy and NYHA class 2 and 3 chronic heart failure (CHF) by Cice et al. (57) was a remarkable accomplishment, as few clinical trials have been conducted on cardiac disease in dialysis patients. The authors reported a sustained objective improvement in LV systolic function (documented by serial echocardiography) at 1 yr, with improvement (P < 0.05) of mean LV ejection fraction from 26 ± 8% to 35 ± 11% versus no change with placebo. Nearly 30% of class 3 CHF patients receiving carvedilol shifted to class 2 compared with no significant improvement after placebo. Cice et al. have recently reported that the 2-yr mortality rate in the placebo group was 73% versus 52% in the carvedilol group (P < 0.01), with a 49% reduction in all-cause death risk with carvedilol and a 56% reduction in all-cause hospitalization risk (58). It has been proposed that prophylactic β-blocker therapy might reduce the cardiovascular mortality of dialysis patients (particularly diabetic patients) (59a). Given the safety of these agents and comparatively modest cost, this would be a worthy subject for a large-scale randomized clinical trial. Clinical trials on antioxidant therapy in the general population have been profoundly disappointing to antioxidant vitamin enthusiasts. In dialysis patients, the issue is less clear, as two randomized clinical trials suggest that cardiovascular events in dialysis patients can be reduced by antioxidant therapy: Vitamin E Secondary Prevention with Antioxidants of Cardiovascular Disease in End-Stage Renal Disease (SPACE trial) (60) and acetylcysteine (61). The degree of oxidative stress is greater in the dialysis population; for this reason, there may be a special niche for antioxidant therapy. Future clinical trials testing the effects of anti-oxidant therapy in dialysis patients are warranted. Cardiac Arrest Sudden cardiac death may be implicated in 60% of all cardiac deaths in dialysis patients, making it potentially the single largest cause of death in dialysis patients. Strategies to reduce the risk of succumbing to this lethal event should concentrate on reducing the likelihood of cardiac arrest and increasing the probability of surviving cardiac arrest (62). The risk of cardiac arrest increases over time after dialysis initiation (vintage effect), with an event rate of 110 events/1000 patient-years at 2 yr, rising to 208 events/1000 patient-years 5 yr after initiation in patients with diabetic ESRD (11). Identification of high-risk patients by assessment of LV function, ischemic burden, and biomarkers (particularly cardiac troponin T) might facilitate targeted intervention in high-risk patients. Treatment with agents known to improve cardiac survival in the general population (e.g., aspirin, β-blockers, ACE inhibitors, statins, etc) might also reduce the risk of sudden cardiac death in ESRD patients. The maintenance of physiologic loading conditions and avoidance of large electrolyte shifts are specific strategies applicable to dialysis patients. Karnik et al. (63) reported a cardiac arrest rate of 7 per 100,000 hemodialysis sessions (with Monday the most likely day for cardiac arrests). Cardiac arrest was nearly twice as likely in patients dialyzed against a 0 or 1.0 mEq/L potassium dialysate on the day of cardiac arrest. Becker et al. (64) reported on cardiac arrest outside hospitals in Seattle and King County from 1990 to 1996 using Emergency Medical Services (EMS) data. There were 47 cardiac arrests in dialysis centers, with an annual incidence of 0.746. Linda Becker has kindly shared with me the dialysis-specific resuscitation data (47 patients), which did not appear in her paper. There were 41 witnessed events, and bystander CPR was administered to 41 patients. In 29 patients (62%), the cardiac rhythm was ventricular fibrillation (VF) or ventricular tachycardia (VT). The overall survival to hospital discharge was 30%; of the patients with VT/VF, it was an impressive 38%. It must be acknowledged that Seattle/King County is widely regarded for its outstanding EMS system; these survival data reflect swift EMS response times and expert crews. These data also make a compelling case for the availability of defibrillators in all dialysis units. The logical conclusion is that automatic external defibrillators (AED), which are widely used (and intended for nonmedical operators), including in all US commercial jet aircraft, some casinos, and many public facilities, should be available in all dialysis centers. The mortality rate is about 10% per min in the first 5 min after cardiac arrest (including with CPR), and survival is uncommon after 10 min—-this is the reason why AED are critical, as EMS response times will always be problematic. Unfortunately, most cardiac arrests occur at home. We have recently presented preliminary data on the apparent striking underutilization of implantable cardioverter defibrillators (ICD) in cardiac arrest survivors on dialysis (65). The 1-yr mortality of 3380 dialysis patients discharged alive from hospital without ICD was 60% compared with 40% in 167 dialysis patients receiving ICD within 30 d of cardiac arrest. In a Cox model, there was a 47% reduction in mortality risk associated with ICD therapy. I believe that a randomized, prospective trial on the efficacy of ICD for the reduction of mortality in dialysis patients would be appropriate. Diagnosis of CAD in ESRD Patients The identification of coronary artery disease in ESRD patients has typically focused on high-risk (predominantly diabetic) renal transplant candidates, despite the fact that a minority of ESRD patients is actually deemed to be transplant candidates. Current practice guidelines address screening for CAD in high-risk renal transplant candidates (66) and waitlisted patients (67), but they do not address the patients at highest risk for cardiac death: dialysis patients not being considered for transplantation. We have previously reported that there is an early hazard of AMI associated with dialysis initiation, as 29% of MI in dialysis patients occur within 1 yr and 52% within 2 yr of initiation of dialysis (31). I would argue that some type of assessment of global cardiac risk would be appropriate after dialysis initiation, provided that testing can guide clinical management (and this is the usual Gordian knot of clinical practice, as the evidence supporting intervention is frequently weak or not existent). The key issue in diagnosis/testing for CAD in ESRD patients is how the clinician will use the resultant information. The ability to accurately predict coronary anatomy on a noninvasive test is not equivalent to the predictive value of the test for prognostication of future cardiac events. When renal transplant candidates are screened for CAD by noninvasive stress imaging tests, one clinical goal is risk stratification for future adverse cardiac events. The second goal is to actually predict coronary anatomy, if prophylactic coronary revascularization is solely based on angiographic findings (68). If restenosis is an issue after PCI, the sensitivity of the stress-imaging test to predict coronary anatomy is important, because there may be no other clinical surrogates to identify occult restenosis. Exercise stress electrocardiog