Renal Artery Stenosis

1. Clinical Practice Renal Artery Stenosis Lance D. Dworkin, M.D., and Christopher J. Cooper, M.D. November 12, 2009 2010년 3월 23일 화요일 신장내과 R4 이완수

2. Case Vignette • Vital sign • BP 160/75 mmHg • HR 60 beats/min • RR 24 breaths/min • Physical Examination • Chest auscultation - diffuse rales • Pitting edema (1+) • Lab. • Serum Creatinine 1.4 mg/dL • (eGFR 52ml/min) • Urinalysis protein 1+ • Age/Sex • 73/male • Chief compliant • shortness of breath  ER visit • Personal History • former smoker • Past History • Hypertension • Dyslipidemia

3. Case Vignette • Condition improves after treatment (IV diuretics) • But, systolic BP remains elevated (170 mmHg) • Magnetic resonance angiography (MRA) • diseased aorta • Lt. renal artery (ostial lesion)  High grade “atherosclerotic stenosis” • Rt. renal artery  normal • How should he be further evaluated and treated? Renal artery stenosis (Lt.)

4. Outline • The Clinical Problem • Strategies and Evidence • Evaluation • Treatment Options • Medical Therapy • Surgical Therapy • Angioplasty and Stenting • Areas of Uncertainty • Guidelines • Conclusions and Recommendations

5. The Clinical Problem • “Renal-artery stenosis” • Definition • narrowing of one or bothrenal arteries or their branches. • Cause • 1. atherosclerosis (most common, 90%) • 2. fibromusculardysplasia (Less frequently) • 3. other causes (rare) • Vasculitis (Takayasu’sarteritis) • Dissection of the renal artery • Thromboembolic disease • Renal artery aneurysm • Renal artery coarctation • Extrinsic compression • Radiation injury

6. Characteristics of Atherosclerotic Renal-Artery Stenosis and Fibromuscular Dysplasia Effective Tx.? controversial balloon angioplasty

7. Prevalence • atheroscleroticrenal artery stenosis in CKD – 0.5~5.5% • true frequency maybe higher (∵ often asymptomatic) • Anatomical progression • occur in more than one third of patients • But, one study • 5 yrs F/U, “Stenosis” “Occlusion “ • only 3~15% patients treated medically • conducted before statin therapy was available Medical treatment is important!!

8. Pathogenesis RAS : renal artery stenosis RBF : renal blood flow

9. Other vascular event? • Renal-artery stenosis ( HTN, CKD)  increasedrisk for vascular events • Explanation?? Uncertain • concomitant atherosclerosis in other vascular beds • activation of the renin–angiotensin–aldosterone • activation of the sympathetic nervous systems • associated renal insufficiency • all these factors chronic kidney disease (25%, vs 2%) coronary artery disease (67% vs 25%) stroke (37% vs 12%) peripheral vascular disease (56% vs 13%)

10. Strategies and Evidence • Classic clinical clues (renal artery stenosis) 1. onset of stage 2 hypertension (BP >160/100mmHg) after 50yrs old 2. family history of hypertension (-) 3. hypertension associated with renal insufficiency (Esp, RAAS inhibition agent  renal fuctionwosens) 4. hypertension with repeated hospital admissions heart failure drug-resistant hypertension (treatment c three drug of different class  BP control fail)

11. Diagnostic Imaging Tests for Renal-Artery Stenosis • Once renal-artery stenosis is suspected?? • confirmation of thediagnosis??  imaging!! ∵ biochemical tests (plasma renin concentrations)  specificity ↓

12. Duplex Ultrasonography in a Patient with Renal-Artery Stenosis • Excellent tool • non-invasive • no apparent side effects • Measurement • “renal-artery velocity” •  functionalassessment • of the “severity of stenosis” • higher velocity •  greater pressure differential • across the stenosis • Limitation • abdominal obesity • bowel gas • technically demanding • (not availableat all centers)

13. Magnetic Resonance AngiographyComputed Tomographic Angiography • High-resolutionmultislice detector devices • Elegant images of the renal arteries and the abdominal aorta • Limitation  may affect image quality • equipment • technique • reconstruction of theimages • patient-related factors • presence of calcium • presence of stents • ability to hold one's breath during imaging • Caution) • CKD patients : toxicity of the contrast medium • nephrogenic systemic fibrosisis associated with gadolinium • nephropathy is associatedwith iodinated contrast dye

14. Rt. renal aterty (arrow) • 70% ostialstenosis • systolic pressure gradient of 28mmHg • Lt. renal artery (arrowhead) • 40% ostialstenosis • pressure gradient of 13mmHg Magnetic Resonance Angiography of the Renal Arteries Showing Severe Bilateral Stenosis

15. Digital subtraction angiography • Best image quality, anatomy information • use of small-diametercatheters and minimal amounts of contrast material reduce the risk of vascular complications and contrast nephropathy • Limitation • invasive • only in experienced centers • contrast nephropathy in CKD • atheroembolic event • vascular complication at punture site • Radation exposure

16. degree of atherosclerosis of the aorta • sizeof the kidney • extent of poststenotic dilatation • rapidity of the appearance and washout of contrast material Useful in diagnosis of Renal artery stenosis “Functional significance” of the lesion ? Predict the “response to revascularzation” ? No conclusive test • nuclear scintigraphy • renin samplingfrom the renal veins • pressure gradients acrossstenoses Kidney (supplied by an occluded renal artey) is viable? Contributing to hypertension ? Stenosis is affecting intrarenal pressure?

17. Treatment Options • Medical Therapy • Surgical Therapy • Angioplasty and Stenting  improved survival improved BP control less impairment of renal function

18. Medical Therapy • Cornerstone of treatment for renal-arterystenosis • Recommendations • Multidrug regimens for BP control • RAAS inhibitor is recommendedin most patients (Renin–angiotensin–aldosteronesystem is often activated in patients with renal-artery stenosis) • alpha-blockeror beta-blocker • long-actingCCB • diuretics • Caution) “Bilateral severe stenosis“ Use of “RAAS inhibitor”  ARF High-grade stenosis in one kidney Advanced chronic kidney disease probability of this complication appears to be low in most cases, it is reversible with the discontinuation of treatment

19. Medical Therapy • Recent data • ACE inhibitor  reduced risk of death • Statin reduction in the severity of renal artery stenosis • Statin c stenting improve survival • Statin, antiplatelet therapy  benefit in patient with atherosclerotic disease

20. Surgical Therapy • Surgical revascularization • durable relief of renal-arterystenosis • improves BP control and kidney function • Safety • recent datahave indicated a 10% in-hospital mortality after this procedureamong Medicare patients • “balloonangioplasty”vs“surgery” • 58 patients with renal-artery stenosis, randomized trial • resulted in similar rates ofcure or improvement in HTN, renal function “nonsurgical revascularization” first-lineapproach (if an intervention is planned)

21. Angioplasty and Stenting • “Fibromuscular dysplasia” • balloon angioplastyremains the preferred form  many patients are able to discontinue all antihypertensive medications • But, medical therapyalone may be appropriate in patients with well-controlled hypertension • “Atherosclerotic renal artery stenosis” • balloon angioplasty • Less effective • Restenosis 71%↑ • 3multicenter trials, without stenting • 1 yr follow-up, no significant improvementin BP • But, controversial

22. Angioplasty and Stenting • Predictors of a favorable outcome of angioplasty • 40 years ↓ at diagnosis • duration of hypertension<5 yrs • systolic BP <160 mmHg

23. Angioplasty and Stenting • Stents • limit elastic recoil • restenosis-free patency ↑ (compared with angioplasty alone) • BP control ↑after stenting

24. Angioplasty and Stenting • Recent trials • 1. comparing stenting plus medicaltherapy with medical therapy alone • preservation of renalfunction • no significant benefits with the addition ofstenting • 2. Angioplasty and Stenting forRenal Artery Lesions (ASTRAL) • stent revascularizationin addition to medical therapy vsmedicaltherapy alone • renal function, mean systolic blood pressure, in rates of renal or cardiovascularevents or death • no significant difference between the study groups at the 5yrs follow-up

25. Angioplasty and Stenting • 3. Stenting in Renal Dysfunction Causedby Atherosclerotic Renal Artery (STAR) trial • prevention of loss of kidney function • serious procedure-related complications • stenting plus medical therapy vsmedical therapyalone • did not showa benefit

26. Angioplasty and Stenting • Revascularization • renin–angiotensin–aldosteronesystem ↓ • sympathetic nervous system ↓ • possible cardiovascularbenefits “pharmacologic therapy”?? directed at these pathways • mayhave similar benefits  improved survival improved BP control less impairment of renal function

27. Areas of Uncertainty Response to revascularization?  no methodreliably predicts Optimaltreatment strategy? “Angioplasty and Stenting” vs “medicaltherapy alone”  remains unclear • Data are lacking • randomizedclinical trials comparing the effects of various medical regimens • Available data from randomized trials • not shown a benefitof “revascularization plus medical therapy” with respect to blood-pressurecontrol and renal function • But, these trials had methodologiclimitations, were not powered for the assessment of cardiovascularoutcomes, and did not include quality-of-life assessments

28. Previous algorithm

29. Cardiovascular Outcomes in Renal Atherosclerotic Lesions(CORAL) study • large, multicenter, randomized,controlled trial • funded by the National Institutes of Health • scheduled to be completed in 2011 • medical therapy plus stent revascularizationvsmedical therapy alone • end point : cardiovascularand renal events • Pending the results of the study • besttreatment for renal-artery stenosis ? • whether to evaluate?  remain uncertain

30. Guidelines • American College of Cardiology–American Heart Association2005 guidelines (for the care of patients with peripheral-arterydisease, including renal-artery stenosis) • Revascularization recommendations • class I evidence (i.e., general agreement on usefulness) • recurrent congestiveheart failure • pulmonary edema • class IIa evidence (i.e., conflicting opinions, but withthe preponderance of evidence favoring usefulness) • global renal ischemia • progressive chronickidney disease • unstable angina • hypertension that is worsening • resistant to medical therapy • malignant • unexplained unilateral small kidney • cannottolerate antihypertensive medication

31. Conclusions and Recommendations • A diagnosis of renal-artery stenosisshould be considered in any patient with a history of severe or resistant hypertension, hypertension that is associated with renal insufficiency, or disease in other vascular beds.

32. Conclusions and Recommendations • Initial examination • measurement of kidney function and a lipid profile • Anatomical diagnosis • duplex ultrasonography • CTA or MRA (if high-quality duplex imaging is not available) • Therapy • intensive medical therapy • tight BP control with a blocker of the RAAS (serum creatinine and potassiumshould be closely monitored) • administration of an antiplateletagent and a statin • Treatment of diabetes and chronic kidneydisease • Revascularizationin the treatment of atherosclerotic renal-artery stenosis ?  controversial