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Pathophysiology of CVD in Patients With CKD
Cardiac Risk Assessment
Cardiac Nuclear Imaging for the Detection of CAD and Risk Stratification



National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification
Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification, published by the National Kidney Foundation


Chronic Kidney Disease and the Risk of CAD

Coronary artery disease (CAD) is a major cause of death in patients with end-stage renal disease (ESRD), with a 15- to 30-times higher age-adjusted rate of CAD than in the general population.1 Cardiovascular disease (CVD) is a major cause of morbidity and mortality among patients with chronic kidney disease (CKD),2,3 whether other risk factors for heart disease are present or not.3 Even patients with early-stage or mild kidney disease have a higher risk of CVD and heart-disease-related death.3

Abnormal single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) results are a strong predictor of all-cause mortality in chronic kidney disease (CKD) patients, adding independent and incremental information to clinical factors, exercise stress electrocardiography (ECG), glomerular filtration rate (GFR), and angiographic parameters.4 Patients with CKD or ESRD may be hospitalized for chest pain symptoms, suspected heart failure, or acute coronary syndromes (ACS), and hospitalists should understand the pathophysiologic connections between CKD and CAD and the most appropriate testing methods to assess the risk of cardiac events in patients with CKD.

Patients with CKD have a higher prevalence of several cardiac risk factors compared with the general population. For example, the prevalence of hypertension among patients with CKD ranges from 60% to 100%.5 Elevated total cholesterol is found in 30% of CKD patients without nephrotic syndrome and 90% of CKD patients with nephrotic syndrome, vs 20% of the general population.5

Renal disease can be either a cause or consequence of CVD, which includes coronary artery disease (CAD), cerebrovascular disease, peripheral vascular disease, and heart failure.6 For example, congestive heart failure can lead to renal failure.6 Likewise, severe hypertension can lead to extensive, and rapidly progressing, renal damage.3

Changes in plasma and extracellular fluid composition associated with renal disease can adversely affect cardiac function. For example, cardiac arrhythmias can result from electrolyte imbalances caused by renal disease. Renal disease can also lead to hyperlipidemia as a result of increased synthesis and decreased clearance of lipoproteins from the body. Patients with CKD typically have increased levels of low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) with little change in high-density lipoproteins (HDL). Renal disease and its consequent hyperlipidemia is a significant risk factor for atherosclerosis and the development of CAD.7

Compared with CVD in the general population, CVD in patients with CKD has an earlier onset, more rapid progression, stronger association with calcification, increased vascular stiffness, resistance to lipid-lowering properties of statins, increased complications with revascularization, and higher rates of sudden death.8 Therefore, early detection and aggressive management of CVD should be a standard component of care for all patients with CKD.9

According to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) evidence-based guidelines, all patients with CKD (either kidney damage or GFR <60 mL/1.73 m2 for >3 months) should be considered in the “highest risk group” for subsequent CVD events. These patients should undergo assessment for traditional and CKD-related CVD risk factors, as listed in Table 1.6 It is recommended that evaluation and treatment interventions based on CVD risk stratification should take into account the “highest-risk” status of this patient population.6

The KDOQI guidelines state that “risk factor reduction is likely to be effective in reducing morbidity and mortality due to cardiovascular disease in patients with chronic kidney disease.”6 Early detection and intervention might prevent or delay cardiovascular adverse events and potentially improve outcomes for this high-risk patient population.9,10

Detecting the extent and severity of myocardial ischemia secondary to CAD provides useful information for the risk stratification and management of patients with varying degrees of renal dysfunction.4 Exercise ECG testing often is limited by the inability of patients with CKD to achieve peak exercise capacity, the potential for exercise-induced hypotension, and the high likelihood of left ventricular hypertrophy, which makes the ECG uninterpretable in many cases.10 Pharmacologic stress SPECT MPI is an option for patients with CKD who are unable to undergo adequate exercise stress.11

In an observational study of 1,652 CKD patients (<60 mL/min/1.732) who underwent SPECT MPI, 68% of patients required pharmacologic stress, as they could not achieve maximal heart rate.4 The annual cardiac death rate was significantly higher among patients with an abnormal SPECT MPI and CKD compared with patients with an abnormal SPECT MPI and no CKD (9.5% vs. 4%, respectively, P<.0001). The presence of perfusion abnormalities was strongly predictive of cardiac death, myocardial infarction, and non-fatal myocardial infarction across all levels of renal dysfunction. This trend was stronger among patients with more severe renal dysfunction.4 Therefore, it has been suggested that SPECT MPI is diagnostically accurate and can be used to risk stratify patients with CKD—even asymptomatic patients—and should be considered for the detection of CAD among patients with renal dysfunction.4,10

This review highlights the prevalence of CVD in patients with CKD, and that CVD is the leading cause of death, regardless of the stage of kidney disease.6 All patients with CKD are at the “highest risk” for CVD, according to the NKF KDOQI evidence-based clinical practice guidelines.6 In addition, the KDOQI guidelines recommend that all patients with CKD undergo routine assessment for CVD because regular screening might help identify CKD patients who would benefit from interventions to reduce CVD risk.

Pharmacologic stress SPECT MPI might be useful for diagnosing CAD and providing information about the risk of future cardiac events in patients with renal disease.4,10 Healthcare professionals should assess the utility of radionuclide MPI for their patients who have CKD and either known or suspected CAD in order to assess their risk of adverse cardiac outcomes and provide appropriate management to reduce this risk.

Matthew Landler, MD, from the Northwestern University Feinberg School of Medicine, is the consultant for The Heart and Hospital Medicine series. Dr. Landler is a consultant for Astellas Pharma US, Inc.


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  1. Brosius FC, Hostetter TH, Kelepouris E, et al. Detection of chronic kidney disease in patients with or at increased risk of cardiovascular disease. Circulation. 2006;114:1083-1087.
  2. USRDS 2009 Annual Data Report. United States Renal Data System website. Available at: www.usrds.org/2009/usrds_booklet_09.pdf. Accessed Nov. 1, 2010.
  3. The kidney and heart disease connection. The American Society of Nephrology website. Available at: www.mcw.edu/FileLibrary/User/kerbach/kidneyheartconnect.pdf. Accessed Nov. 1, 2010.
  4. Hakeem A, Bhatti S, Dillie KS, et al. Predictive value of myocardial perfusion singe-photon emission computed tomography and the impact of renal function on cardiac death. Circulation. 2008;118:2540-2549.
  5. Gupta R, Birnbaum Y, Uretsky BF. The renal patient with coronary artery disease. J Am Coll Cardiol. 2004;44:1343-1353.
  6. National Kidney Foundation. KDOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39:S1-S266.
  7. Kidney Disease and Diabetes. The American Heart Association website. Available at: www.heart.org/HEARTORG/Conditions/Diabetes/WhyDiabetesMatters/Kidney-Disease-Diabetes_UCM_313867_Article.jsp. Accessed Jan. 7, 2011.
  8. Hage FG, Zoghbi GJ, Perry GJ, DeMattos AM, Iskandrian AE. The scope of coronary heart disease in patients with chronic kidney disease. J Am Coll Cardiol. 2009;53:2129-2140.
  9. Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med. 2003;139:137-147.
  10. Okwuosa T, Williams KA. Coronary artery disease and nuclear imaging in renal failure. J Nucl Cardiol. 2006;13:150-155.
  11. Hase H, Joki N, Ishikawa H, et al. Prognostic value of stress myocardial perfusion imaging using adenosine triphosphate at the beginning of haemodialysis treatment in patients with end-stage renal disease. Nephrol Dial Transplant. 2004;19:1161-1167.

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