RAS Epidemiology. Renal Artery Stenosis. Pathophysiology of RAS. Disclosure of Potential Conflicts. Background Pathophysiology of RAS.

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1 Renal Artery Stenosis 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% Alexander S. Yevzlin, MD Associate Professor of Medicine (CHS) ASDIN 2012 Prevalence increases with age: 7% over 65 years old Disclosure of Potential Conflicts Pathophysiology of RAS Cytopherx, Inc. R4 Vascular, Inc. Bard Peripheral Vascular Courtesy of V. Chhokar Background Road Map Defining the Controversy The Nephrologists Perspective A More Selective Approach Background Pathophysiology of RAS Other actions of angiotensin II (Ang II) promote pressor mechanisms, vascular remodeling, cardiac dysfunction, and tissue fibrosis. 1

2 Background Progression of Disease RAS > 50% Ischemic Nephropathy (no fibrosis resulting from hemodynamic changes) Ischemic Nephropathy RAS > 50% (small vessel disease) 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. * * 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 : , The Controversy RAS Interventions Why Are Nephrologists Averse to Nephrologists have moved toward a more conservative clinical stance in recent years, perhaps as a pragmatic counterweight to enthusiastic interventional specialties. * The largest portion of this increase derives from procedures undertaken by cardiologists.* * 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 : , 2007 * Murphy TP, Soares G, Kim M: Increase in utilization of percutaneous renal artery interventions by Medicare beneficiaries Am J Roentgenol 183 : , 2004 The Controversy 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. 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: ; W 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:

3 A possible explanation for the recent RAS clinical trial findings is that these studies included patients who had little chance to improve anyway. Fifteen years experience of treating Atherosclerotic Renal Artery Stenosis by Interventional Nephrologists in India Overall, the observational study by Hegde et al witnessed improvement in renal function in 10% and stabilization in 60% of the subjects. Estimated glomerular filtration rate (egfr) improved significantly in bilateral RAS, and egfr improved or stabilized in % of the subjects. The authors noted a > 90% technical success rate.how do these findings compare to existing observational studies? It is important to mention that such studies have reported mixed results vis-à-vis renal function. Why Are Nephrologists Averse to New Algorithm 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 Risk Factors for Outcomes Pre-intervention GFR Initial size of the treated kidney Vascular resistive index Patient age Lateralization to the affected kidney Otcomes 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: 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: 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: 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:

4 2/29/2012 Outcomes 4

5 Thank you 5

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