08-1 Renovascular Disease: Core Curriculum

08-2 Renal Artery Stenosis Etiology + Pathophysiology Incidence Diagnosis Indications for Revascularization Treatment Options - Medical Therapy - PTA - Surgical Technical Considerations Complications Prognosis

08-3 Causes of Ischemic Renal Disease Atherosclerotic Renal Artery Stenosis Fibromuscular dysplasia Nephroangiosclerosis (HTN injury) Diabetic nephropathy (small vessels) Renal thromboembolic disease Atheroembolic renal disease Aortorenal dissection Post renal transplant RAS Renal artery vasculitis Trauma Neurofibromatosis Thromboangiitis obliterans Scleroderma #1 Renal Artery Stenosis #2 Fibromuscular Dysplasia

08-4 Atherosclerotic Renal Artery Stenosis Atherosclerosis accounts for approximately 90% of the cases of RAS and is the predominant lesion detected in patients >50 years of age The presence and number of diseased coronary arteries predicts the likelihood of ARAS RAS resulting from atherosclerotic disease is common in (18% to 20%) individuals undergoing coronary angiography 1 RAS resulting from atherosclerotic disease is even more common (35% to 50%) in individuals undergoing peripheral vascular angiography for occlusive disease of the aorta and legs 2 1. Rihal et al Mayo Clin Proc 2002; 77: 309– Olin et al J Vasc Surg 2002; 36: 443–451

08-5 Fibromuscular Dysplasia (FMD) Unknown etiology Second most common cause of RAS Affects middle-aged women More common in first-degree relatives and in the presence of the ACE-I allele. Renal artery involvement is seen in 60% of cases - frequently bilateral compromise. Progressive renal stenosis is seen in 37% of cases and loss of renal mass in 63% Grossmans “Catheterization” 7 th Ed. pg

08-6 A.Classic “string of beads” appearance of fibromuscular dysplasia. B.Intravascular ultrasound (IVUS) with a 40-MHz catheter demonstrating multiple fine fibrous bands and foci of interband aneurysmal dilatation. C.Translesional gradient measured between a 6Fr guide catheter placed in the aorta and a 4F glide catheter placed in the distal renal artery. A 60-mm Hg resting gradient is demonstrated. Grossmans “Catheterization” 7 th Ed. pg

08-7 Fibromuscular Dysplasia (FMD) Treatment Balloon angioplasty alone: FMD localized within the main renal artery or its primary branches Stenting: Reserved for failure or complications of balloon angioplasty Surgery: FMD that involves multiple branch vessels or is associated with aneurysmal disease Grossmans “Catheterization” 7 th Ed. pg

08-8 D.Post-balloon angioplasty with a 4.5mm diameter balloon demonstrating improvement in the angiographic appearance. E.Intravascular ultrasound (IVUS) confirms the postangioplasty improvement F.Postprocedure IVUS demonstrates fracture of the fibrous bands, resulting in resolution of the gradient seen before the procedure. Grossmans “Catheterization” 7 th Ed. pg

08-9 Garovic VD, Textor SC. Circulation 2005;112: Schematic of Pressor Mechanisms Identified in Renovascular Hypertension

08-10 “Goldblatt” Model (1934) FMD Model:“Atherosclerotic” Model (1970’s): No comorbidityNo comorbidity Hypertension outHypertension out of context Sole mechanism ofSole mechanism of hypertension Young patients (female) Limited comorbidity Hypertension out off context (detection) Sole mechanism of Hypertension Older patients Associated comorbidity Hypertension in context

08-11 Renal Artery Stenosis Etiology + Pathophysiology Incidence Diagnosis Indications for Revascularization Treatment Options - Medical Therapy - PTA - Surgical Technical Considerations Complications Prognosis

08-12 Prevalence of Renal Artery Stenosis Most Common Cause of 2 o HTN All HTN Pts >50 yrs With ESRD Pts with CAD Acc HTN Aortography For PAD 5-10% 15% 20% 30% 50-59% Rihal et al Mayo Clin Proc 2002; 77: 309–316 Olin et al J Vasc Surg 2002; 36: 443–451

08-13 Prevalence of Renal Artery Stenosis 834 patients undergoing ultrasound screening Mean age of 77 years Significant (>60%) RAS in 6.8% of the study cohort 2 x as many men (9.1%) as women (5.5%, P=0.053) RAS showed no association with ethnicity, even distribution among white (6.9%) and black (6.7%) participants RAS was significantly and independently associated with increasing age, low high-density lipoprotein cholesterol levels, and increasing systolic blood pressure. Hansen et al J Vasc Surg 2002;36:443-51

08-14 Buller CE et al JACC 2004: 43:1606 Severe Renal Artery Stenosis Multivariate Associations Multivariate Associations 837 patients undergoing screening angiography

08-15 Incidence of Renal Artery Stenosis at Cardiac Catheterization Study AuthorsPatients,n Any RAS,% RAS >50%,%Bilateral, % Aqel et al90NR2810 Weber-Mzell et al Rihal et al Vetrovec et al Harding et al Jean et al NR Mean±SD ±3.619±617.4±14.2 RAS indicates renal artery stenosis; NR, not reported. White, C. J. Circulation. 2006;113:

08-16 Approximately 50% of renal artery stenoses progress over time

08-17 Progression Of RAS Disease progression is associated with a decline in renal function Crowley JJ et al Am Heart Journal 1998;136: ± 44 μmol/L 141 ± 114 μmol/L Patients with normal renal arteries at baseline

08-18 Progression of Renovascular Disease Results in Renal Atrophy 204 kidneys in 122 patients with RAS 6 monthly serial duplex scanning Defined as > 1cm reduction in length 2 year incidence of renal atrophy: Normal RA5.5% < 60 % stenosis11.7% > 60 % stenosis20.8% Risk of atrophy increased by systolic hypertension (> 180mm Hg) and a high peak systolic velocity Caps et al, Kidney International, 1998

Year Mortality 1235 cath lab patients screened for RAS > 50% Conlon PJ et al, J Am Soc Nephrol 9:252;1998 Multivariable Predictors Age Gender GFR (per 5 ml/min) SBP (per 5 mmHg) Abdominal or LE Disease Carotid Disease OR P Value

08-20 Renal Artery Stenosis Etiology + Pathophysiology Incidence Diagnosis Indications for Revascularization Treatment Options - Medical Therapy - PTA - Surgical Technical Considerations Complications Prognosis

08-21 Garovic VD, Textor SC Circulation. 2005;112:

08-22 Renal Artery Obstruction The Dilemma of Diagnosis Atherosclerosis, hypertension and renal insufficiency exist and co-exist commonly. When there is renal artery stenosis: Is it the cause of hypertension? Is it the cause of renal insufficiency? Will treatment improve either? Will treatment prevent deterioration?

08-23www.Cardiosource.com. ACC/AHA Guidelines

08-24www.Cardiosource.com. ACC/AHA Guidelines

08-25 Noninvasive diagnostic modalities Renal Artery Ultrasound Body habitus dependent Operator dependent May miss accessory arteries No additional anatomical information Physiological information Allows post intervention surveillance

y/o man with difficult to control HTN

08-27 Duplex Assessment of RAS Duplex CriteriaStenosis RAR<3.5 and PSV<200 cm/sec 0-59% RAR >3.5 and PSV>200 cm/sec 60-99% RAR>3.5 and EDV > 150 cm/sec 80-99% Absence of flow and low amplitude parenchymal signal Occluded

08-28 Power Doppler image of a stenosis of right RA. The arrows indicate the stenosis. Manganaro et al. Cardiovascular Ultrasound :1

y/o woman with well controlled HTN Noninvasive diagnostic modalities Digital Subtraction Angiography

08-30 Noninvasive diagnosis: MRA Identifies accessory renal arteries Provides additional anatomical information No radiation No nephrotoxic contrast Allows 3-D reconstruction May “overcall” lesions Looses accuracy in distal segments (FMD) Mild (30%) left RAS and severe (90%) right RAS in 70-year-old man Fenchel, M. et al. Radiology 2006;238:

08-31 Herborn, C. U. et al. Radiology 2006;239: Severe stenosis of left renal artery in a 72 y/o man Normal renal arteries in a 61 y/o man

y/o woman with well controlled HTN

y/o man with difficult to control HTN Motion artifact

08-34 Renal Artery Stenosis Etiology + Pathophysiology Incidence Diagnosis Indications for Revascularization Treatment Options - Medical Therapy - PTA - Surgical Technical Considerations Complications Prognosis

08-35 Reasons to Revascularize Atherosclerotic Renovascular Disease Treat Symptoms Treat Symptoms Prevent Future Illness Prevent Future Illness Lower BP Lower BP Preserve Renal Function Preserve Renal Function “Bystander” Effects “Bystander” Effects - Prevent Death - Prevent MI - Prevent MI - Prevent CHF - Prevent CHF - Prevent CVA - Prevent CVA

08-36 Indications for Revascularization of RAS Circulation 2005;112: Resistant hypertension -Failure of medical therapy despite full doses of 3 drugs, including diuretic - Compelling need for ACE inhibition/angiotensin blockade with angiotensin-dependent GFR 2.Progressive renal insufficiency with salvagable kidneys -Recent rise in serum creatinine -Loss of GFR during antihypertensive therapy (e.g., ACEI) -Evidence of preserved diastolic blood flow (low resistive index) 3.Circulatory congestion, recurrent “flash” pulmonary edema 4.Refractory congestive heart failure with bilateral renal artery stenosis

08-37 Who Will Benefit: Renal Resistive Index Reflection of intrarenal vascular surface area and resistance Calculated using Doppler U/S Resistive Index [1-(EDV/PSV)]x patients underwent U/S calculation of renal resistive index 138 RAS patients treated Followed for improvement in BP and Cr Radermacher et al NEJM. 2001;344:

08-38 Outcomes Predicted By RRI Radermacher et al NEJM. 2001;344:

08-39 Renal Revascularization Useful when: Renal artery stenosis is SEVERE, and... Renal function is “salvageable” Preserved size Preserved intrinsic vasculature (“low” RI) Not useful when: Renal artery stenosis is not severe Renal function is “unsalvageable” Unknown: Prophylactic use Value of screening Role of atheroembolization / Protection

08-40 Renal Artery Stenosis Etiology + Pathophysiology Incidence Diagnosis Indications for Revascularization Treatment Options - Medical Therapy - PTA - Surgical Technical Considerations Complications Prognosis

08-41 Goals Of Renal Artery Revascularization Improve control of hypertension Preserve or restore renal function Treat other potential adverse physiologic effects of severe renal artery stenosis (congestive heart failure, recurrent flash pulmonary edema, and angina)

08-42 ACE inhibitors are effective medications for treatment of hypertension associated with RAS. Calcium-channel blockers are effective medications for treatment of hypertension associated with unilateral RAS. Beta-blockers are effective medications for treatment of hypertension associated with RAS. Pharmacological Treatment of Renal Artery Stenosis Angiotensin receptor blockers are effective medications for treatment of hypertension associated with unilateral RAS. ACC/AHA Guidelines

08-43 Catheter- Based Interventions for RAS Renal stent placement is indicated for ostial atheroesclerosic RAS lesions that meet the clinical crietria for intervention. Balloon angioplasty with “bail-out” stent placement if necessary is recommended for fibromuscular dysplasia lesions. ACC/AHA Guidelines

08-44 Zeller T. Journal of Interv Card 18 (6), Renal Artery Stent Placement Ostial atheroma Stent with protrusion into aortic lumen 2 mm into aorta

08-45 Renal Artery Stenting: Results Published series before 1998 Leertouwer et al Radiology 2000, patients, mean follow up 16 months Hypertension cured 20% Hypertension improved 49% Renal function improved 30% Renal function stabilized 38% 69% 78%

08-46 Renal Artery Stenting Studies –Meta-analysis of 349 pts in 8 clinical series -Hypertension improved in 56%; cured in 10% -Renal artery function improved in 27%; stabilized in 38% -Restenosis occurred in 16% -Major complications in 4.9 Palmaz JC et al J Vasc Intervent Radiol 1998;9: –DRASTIC Trial -106 patients treated with PTA or medical therapy -Although no difference in outcomes, stenting reserved for “bailout”, 44% of medical therapy crossed over to PTA due to HTN, occlusion seen in 16% of medical treated patients Van Jaarsveld BC et al. N Engl J Med 2000; 342:

08-47 White CJ Circulation 2006;113: Superiority of renal artery stent compared with balloon angioplasty for procedure success and restenosis rates Restenosis Percent Procedure Success

08-48 Surgery for Renal Artery Stenosis Endarterectomy Aortorenal bypass Extra-anatomic bypass using hepatorenal, splenorenal, ileorenal, or superior mesenteric artery – renal anastomosis.

08-49 Surgery for Renal Artery Stenosis Atherosclerotic RAS in combination with pararenal aortic reconstructions (in treatment of aortic aneurysms or severe aortoiliac occlusive diseease. Fibromuscular dysplastic RAS with clinical indications, especially those exhibiting complex disease that extends into the segmental arteries and those having macroaneurysms. Atheroeclerotic RAS and clinical indications for intervention, especially those with multiple small renal arteries or early primary branching of the main renal artery. ACC/AHA Guidelines

08-50 Renal Artery Stenosis Etiology + Pathophysiology Incidence Diagnosis Indications for Revascularization Treatment Options - Medical Therapy - PTA - Surgical Technical Considerations Complications Prognosis

08-51 Renal Arteriography Abdominal Aortogram: identification of ostia of the renal arteries and accessory renal arteries (25% of population) Arteriography should include both the arterial phase and the nephrographic phase Disease involving renal bifurcations require cranial or caudal angulation to open out the lesion Evidence of aortic atheroma: technique of no-touch angiography is recommended IVUS provides a further method of renal artery evaluation for indeterminate lesions

08-52 Brachial Approach For renal arteries that are oriented cephalad. When the aorta is occluded distally or the renal artery takeoff is severely angulated Proximal renal artery segment initially courses inferiorly and posteriorly braquial approach allows more coaxial alignment. Greater incidence of vascular site complications Zeller T. Journal of Interventional Cardiology 18 (6),

08-53 Femoral Approach Renal artery angioplasty and stenting are usually performed via retrograde femoral approach. When the real artery origin is oriented horizontally or caudally with respect to the aorta, femoral approach is preferred.

08-54 Renal Artery Stenosis Etiology + Pathophysiology Incidence Diagnosis Indications for Revascularization Treatment Options - Medical Therapy - PTA - Surgical Technical Considerations Complications Prognosis

08-55 Registry Stent Complications Renal Stents Blum Harjai Tuttle Rocha-Singh Burket White Borros Total Number Death <1% Dialysis <1% Major Compls %

08-56 Complications Of Percutaneous Renal Revacularization Atheroembolism into the renal or peripheral vascular bed cholesterol embolization Dissection of renal artery or the wall of the aorta Acute or delayed thrombosis Infection Rupture of renal artery Renal perforation

08-57 Complication Rates for Renal Stent Placement Study Authors Patients, nDeath, %Dialysis, % Major complications, % Rocha-Singh et al Tuttle et al White et al Burket et al Dorros et al Total795<1% 2.0% Major complications include death, myocardial infarction, emergency surgery, need for dialysis, or blood transfusion. White et al, Circulation. 2006;113:

08-58 Atheroembolization Protection What is the cause of deterioration in renal function after revascularization? Iodinated contrast?Iodinated contrast? Atheroembolization?Atheroembolization? Something else?Something else? What is the cause of deterioration in renal function after revascularization? Iodinated contrast?Iodinated contrast? Atheroembolization?Atheroembolization? Something else?Something else?

08-59 Filterwire Embolic Protection

08-60 White CJ Circulation 2006;113: A, Baseline selective renal angiogram showing tight ostial stenosis with normal filling of the renal arteries to the cortex B, Poststent angiogram with poor filling of the distal renal arteries caused by embolization Renal Artery Embolization

08-61 Renal Artery Stenosis Etiology + Pathophysiology Incidence Diagnosis Indications for Revascularization Treatment Options - Medical Therapy - PTA - Surgical Technical Considerations Complications Prognosis

08-62 Favorable Predictors Successful Outcome For Control Of Hypertension Rapid acceleration of hypertension over the prior weeks or months Presence of “malignant” hypertension Hypertension in association with flash pulmonary edema Contemporaneous rise in serum creatinine Development of azotemia in response to ACE inhibitors administered for control of hypertension.

08-63 Favorable Predictors Successful Salvage Or Preservation Of Renal Function Recent rapid rise in creatinine, unexplained by other factors Azotemia resulting from ACE inhibitors Absence of diabetes or other cause of intrinsic kidney disease Presence of global renal ischemia, wherein the entire functioning renal mass is subtended by bilateral critically narrowed renal arteries or a vessel supplying a solitary kidney.

08-64 Unfavorable Predictors Renal atrophy demonstrated by kidney length <7.5 cm on ultrasound High renal resistance index detected by duplex ultrasound Proteinuria > 1gm/day Hyperuricemia Creatinine clearance <40 mL/minute

08-65 Outcomes Following Renal Stenting Major Predictor was the RRI Radermacher et al NEJM. 2001;344:

08-66 Outcomes Following Renal Stenting Major Predictor was the RRI at 32 months Radermacher et al NEJM. 2001;344: ↓ MAP ≥ 10 mm Hg ↓ Cr Cl ≥ 10% Dialysis Death RRI < 80 N = 96 94% 3% RRI > 80 N = 35 3% 80% 46% 29% P < for all outcomes

08-67 Harden et al. Lancet 1997;349:1133 Stabilization of Renal Function

08-68 Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) Enrollment: April 2004 – March patients with RAS >60% and hypertension (>155 mmHg on ≥ 2 meds) Composite cardiovascular and renal endpoint: Cardiovascular or renal death, MI, hospitalization for CHF, stroke, doubling of serum creatinine level, need for renal replacement therapy Optimal medical therapy alone vs stenting with optimum medical therapy 1:1 Randomization to:

08-69 Renal Artery Stenosis Etiology + Pathophysiology Incidence Diagnosis Indications for Revascularization Treatment Options - Medical Therapy - PTA - Surgical Technical Considerations Complications Prognosis