Renal Artery Stenosis Disclosure of Potential Conflicts Cytopherx, Inc. R4 Vascular, Inc. Bard Peripheral Vascular Spectranetics, Inc. Alexander S. Yevzlin, MD Associate Professor of Medicine (CHS) ASDIN 2011 Road Map Background Defining the Controversy The Nephrologists Perspective A Different Approach Case Discussion Future Directions RAS Epidemiology Common Disease Incidence General Population 0.1% Hypertensive Population 4% HTN & Suspected CAD 10-20% Malignant HTN 20-30% Malignant HTN and CKD 30-40% Prevalence increases with age: 7% over 65 years old Background Clinical Findings of RAS HTN Abrupt onset before 50 (FMD) Abrupt onset after 50 Accelerated or Malignant HTN Refractory HTN ( 3 drugs) Others PVD or > 2 vessel CAD Renal abnormalities Unexplained Azotemia Azotemia after ACE I Unilateral Small Kidney Unexplained dhypokalemia Cardiac Disturbance Syndromes Pulmonary edema Angina 1
Pathophysiology of RAS Background Pathophysiology of RAS Other actions of angiotensin II (Ang II) promote pressor mechanisms, vascular remodeling, cardiac dysfunction, and tissue fibrosis. Courtesy of V. Chhokar Background Progression of Disease RAS > 50% Ischemic Nephropathy (no fibrosis resulting from hemodynamic changes) The Controversy To intervene or not to intervene? that is the question And when? Medical Therapy Intervention Ischemic Nephropathy RAS > 50% (small vessel disease) The Controversy 35000 30000 25000 20000 15000 10000 5000 0 1996 2000 2005 RAS Interventions The Controversy The largest portion of this increase derives from procedures undertaken by cardiologists.* * Murphy TP, Soares G, Kim M: Increase in utilization of percutaneous renal artery interventions by Medicare beneficiaries 1996 2000. Am J Roentgenol 183 : 561 568, 2004 2
Why Are Nephrologists Averse to RAS Intervention? It is almost certain that many, if not most, patients now being subjected to endovascular stenting of the renal arteries have only limited benefit, regarding either BP response or improvement in kidney function. * Why Are Nephrologists Averse to RAS Intervention? Nephrologists have moved toward a more conservative clinical stance in recent years, perhaps as a pragmatic counterweight to enthusiastic interventional specialties. * * Levin a, Linas SL, Luft FC, Chapman AB, Textor SC: Controversies in renal artery stenosis: A review by the American Society of Nephrology Advisory Group on Hypertension. Am J Nephrol 27 : 212 220, 2007 * Levin a, Linas SL, Luft FC, Chapman AB, Textor SC: Controversies in renal artery stenosis: A review by the American Society of Nephrology Advisory Group on Hypertension. Am J Nephrol 27 : 212 220, 2007 Why Are Nephrologists Averse to RAS Intervention? Several large randomized controlled trials (RCTs) have evaluated medical therapy versus PTRAS. The results of the STAR study showed no difference in progression of renal failure in patients with impaired renal function. This has been confirmed by the results of the ASTRAL study. Why Are Nephrologists Averse to RAS Intervention? A possible explanation for the recent RAS clinical trial findings is that these studies included patients who had little chance to improve anyway. Bax L, Woittiez AJ, Kouwenberg HJ, Mali WP, Buskens E, Beek FJ, et al. Stent placement in patients with atherosclerotic renal artery stenosis and impaired renal function: a randomized trial. Ann Intern Med 2009; 150:840 848; W150-1. Schwarzwalder U, Hauk M, Zeller T. RADAR: a randomised, multicentre, prospective study comparing best medical treatment versus best medical treatment plus renal artery stenting in patients with haemodynamically relevant atherosclerotic renal artery stenosis. Trials 2009; 10:60. Wheatley K, Ives N, Gray R, Kalra PA, Moss JG, Baigent C, et al. Revascularization versus medical therapy for renal-artery stenosis. N Engl J Med 2009; 361:1953 1962. Why Are Nephrologists Averse to RAS Intervention? A recognized drawback of clinical treatment trials is the intermixture of high-risk and low-risk patients into the "average" of the entire cohort.* A definition of the RF associated with good and bad outcomes is necessary. * Kent D, Hayward R: When averages hide individual differences in clinical trials. Am Sci 95 : 60 68, 2007 Future Directions The subset of patients with "critical" renal artery stenosis stand to have major clinical benefit from restoring kidney perfusion and major adverse outcomes if not detected and treated. * The definition of "critical " in the recent literature has been radiographic and/or hemodynamic, rather than pathological or epidemiological. *Textor SC, Wilcox CS: Renal artery stenosis: A common, treatable cause of renal failure? Annu Rev Med 52 : 421 442, 2001 3
Risk Factors for Outcomes Pre-intervention GFR Initial size of the treated kidney Vascular resistive index Patient age Lateralization to the affected kidney New Algorithm Zeller T, Muller C, Frank U, Burgelin K, Horn B, Schwarzwalder U, et al. Stent angioplasty of severe atherosclerotic ostial renal artery stenosis in patients with diabetes mellitus and nephrosclerosis. Catheter Cardiovasc Interv 2003; 58:510 515. Radermacher J, Chavan A, Bleck J, Vitzthum A, Stoess B, Gebel MJ, et al. Use of Doppler ultrasonography to predict the outcome of therapy for renalartery stenosis. N Engl J Med 2001; 344:410 417. Krijnen P, van Jaarsveld BC, Deinum J, Steyerberg EW, Habbema JD. Which patients with hypertension and atherosclerotic renal artery stenosis benefit from immediate intervention? J Hum Hypertens 2004; 18:91 96. van Jaarsveld BC, Krijnen P, Pieterman H, Derkx FH, Deinum J, Postma CT, et al. The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery stenosis. Dutch Renal Artery Stenosis Intervention Cooperative Study Group. N Engl J Med 2000; 342:1007 1014. Case Presentation: RAS 59 yo female with DM, RCC s/p right nephrectomy, CKD, CAD, now requiring i CABG. Sent for evaluation of RAS found on MRA. Cr = 2.2. 4
Renal arttery intervention CABG 2.5 2 1.5 1 Creatinine 0.5 0 5
Summary The assertion that RAS should be treated only medically simply does not follow from the published data. The key element of RAS management is to distinguish those who are likely to benefit from intervention from those who are not. General Nephrologists can play a leading role in RAS evaluation. Interventional Nephrologists can play a leading role in RAS intervention. Thank you 6