Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology Regadenoson Use in Chronic Kidney Disease and End-Stage Renal Disease: A Focused Review Aviral Vij, MD1 Yasmeen Golzar, MD1 Rami Doukky, MD, MSc, FASNC1,2 1. Division of Cardiology, Cook County Health and Hospitals System, Chicago, IL 2. Division of Cardiology, Rush University Medical Center, Chicago, IL Copyright American Society of Nuclear Cardiology

Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology Background Regadenoson has been shown to be a safe and effective pharmacologic stress agent in patients with diverse co-morbid conditions. Considering that regadenoson is predominantly renally excreted, its use in patients with kidney disease has been a subject of active post marketing clinical research. The FDA has recently outlined the use of regadenoson in patients with ESRD in a label update on January 17, 2017. Copyright American Society of Nuclear Cardiology

Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology Pharmacokinetics Regadenoson has a prolonged elimination half-life in CKD patients, but it is unlikely to be of clinical significance. Regadenoson is dialyzable, but hemodialysis results in insignificant clearance compared to non-renal elimination mechanism. Gordi T, et al. J Clin Pharmacol. 2007;47(7):825-33 Copyright American Society of Nuclear Cardiology

Safety and Tolerability in CKD/ESRD Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology Safety and Tolerability in CKD/ESRD Aside for experiencing a significantly higher frequency of GI symptoms, ESRD patients have a similar adverse effect profile with regadenoson as patients without ESRD Rates of Adverse Effects within 24 Hours of Regadenoson Stress in Patients with ESRD. ESRD, end-stage renal disease; GFR, glomerular filtration rate (mL/min/1.73m2) Doukky et al. J Nucl Cardiol. 2013;20(2):205-13. Copyright American Society of Nuclear Cardiology

Aminophylline Use in CKD/ESRD Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology Aminophylline Use in CKD/ESRD Patients with severe CKD (stage 4 and ESRD) preferentially benefit from aminophylline administration in reducing regadenoson-related side effects, particularly GI symptoms. Aminophylline does not seem to attenuate the burden of myocardial ischemia or the prognostic value of SPECT-MPI. Rangel MO. J Nucl Cardiol. 2013;22(5):1008-18 Fughhi I, et al. J Nucl Cardiol. 2016; 10.1007/s12350-016-0506-3 Copyright American Society of Nuclear Cardiology

Prognostic Value in CKD/ESRD Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology Prognostic Value in CKD/ESRD Kidney disease is an independent predictor of outcome. CKD/ESRD patients have an increased rate of mortality and adverse cardiac events, regardless of the presence or severity of SPECT defects. Regadenoson stress MPI provides significant prognostic value in patients with CKD. CD, cardiac death; CHF, congestive heart failure; GFR, glomerular filtration rate (mL/min/1.73m2); MI, myocardial infarction; SSS, summed stress score. Bhatti S, et al. Eur Heart J Cardiovasc Imaging. 2014;15(8):933-40. Copyright American Society of Nuclear Cardiology

Prognostic Value of HRR in CKD/ESRD Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology Prognostic Value of HRR in CKD/ESRD Blunted heart rate response (HRR) to A2A receptor agonists has been shown in various studies to be a predictor of worse outcomes. Renal impairment does not alter the prognostic utility of HRR to regadenoson stress. ESRD has been shown to be a predictor of new impaired HRR during longitudinal follow-up which has adverse prognostic significance.  Hage et al. J Nucl Cardiol. 2011; 18(6):1086-94. AlJaroudi et al. J Nucl Cardiol. 2016; 23(3): 560-9. Gomez et al. J Nucl Cardiol. 2017; DOI:10.1007/s1250-017-0802-6. Copyright American Society of Nuclear Cardiology

Role Of Regadenoson MPI In Renal Transplant Patients Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology Role Of Regadenoson MPI In Renal Transplant Patients The AHA/ACCF consensus statement on the cardiac assessment of kidney transplant candidates proposed 8 risk factors for cardiac disease in renal transplant candidates. Having 3 or more risk factors may be an optimal threshold to identify patients in whom stress MPI, including regadenoson stress, provide incremental diagnostic value for obstructive CAD. Stress MPI, including regadenoson stress, provided incremental prognostic value for cardiac death or MI in patient with 3 or 4 AHA/ACCF risk factors, but not in low (0 – 2 risk factors) or high (5 – 8 risk factors) risk patients. Lentine KL, et al. J Am Coll Cardiol. 2012; 60 (5): 434-80. Doukky et al. J Nucl Cardiol. 2017; DOI: 10.1007/s12350-017-0901-4. Copyright American Society of Nuclear Cardiology

Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology Summary Although regadenoson is renally excreted, its prolonged elimination half life in patients with kidney disease does not seem to be of clinically significance There is considerable evidence to support the safety of regadenoson in advanced kidney disease, including those with ESRD. Regadenoson can be given to patients with ESRD without dose adjustment Aminophylline can be effectively used to prevent or treat regadenoson-induced adverse effects without affecting the diagnostic utility of MPI images CKD is an independent predictor of outcomes irrespective of traditional risk factors and MPI. Regadenoson MPI provides significant prognostic data in CKD and ESRD patients, including kidney transplant candidates. Blunted HRR to regadenoson can provide additional risk stratification beyond MPI, particularly in patients with normal MPI. Copyright American Society of Nuclear Cardiology