Renal artery stenosis

Renal artery stenosis is the leading cause of secondary hypertension and may lead to :
Resistant (refractory) hypertension,
Progressive decline in renal function, and
Cardiac destabilization syndromes (Flash pulmonary edema, recurrent heart failure, or acute coronary syndromes)

1. Renal artery stenosis Dr najeeb u sofi lps institute of cardiology

2. NORMAL RENAL ARTERIAL ANATOMY Originate from the lateral sides of the aorta at the level of the superior border of the second lumbar vertebra directed slightly anteriorly usually 1-2 cm below the superior mesenteric artery origin . The right RA originates from the anterolateral aspect of the aorta and immediately turns posteriorly to course beneath the inferior vena cava. The left RA originate from the posterolateral surface of the aorta and courses posteriorly the surface of the aorta and over the psoas muscle.

3. R enal artery stenosis is the leading cause of secondary hypertension and may lead to : R esistant (refractory ) hypertension , Progressive decline in renal function , and C ardiac destabilization syndromes (Flash pulmonary edema , recurrent heart failure, or acute coronary syndromes )

4. Renal Artery Stenosis Atherosclerotic (90%) Fibromuscular dysplasia (10%) Aortorenal dissection Vasculitis involving the renal artery (i.e. PAN) AVMs involving the renal artery Irradiation of the renal artery Neurofibromatosis Scleroderma

5. Atherosclerotic RAS Patient 6th decade or older. More often male Associated with diseased aorta Typically involves the ostium and/or proximal one-third of the renal Can be unilateral or bilateral 70-80 % have unilateral disease

6. Fibromuscular Dysplasia Young patients –more commonly females . Commonly asymptomatic Prevalence 2-6 % Renal artery involvement is seen in 60% of cases >60 % of patients have bilateral disease . Medial fibroplasia (90%)>> Intimal (10%) or adventitial Location: distal two-thirds of main renal artery , in 25%, disease extends into segmental arteries R ight renal artery is affected more frequently Progressive renal stenosis is seen in 37% of cases and loss of renal mass in 63 %. Other arteries can also be involved (carotid, vertebral, iliac , and mesenteric). All patients need head imaging to r/o cerebral aneurysms

7. Abdominal aortogram revealed a left renal artery fibromuscular dysplasia with the typical “string of beads” appearance

8. Prevalence of Atherosclerotic RAS M.C secondary cause of of HTN 2-5 % General population 0.1% Hypertensives 1-4% Aged 65 years and older 6.8 % Diabetics 8% Malignant HTN 20 - 30% Malignant HTN & renal insufficiency 30 - 40% 6.8% in healthy adults > 65 years old Evaluation with renal artery duplex of 834 patients consecutive patients who were participants in the Forsyth county cohort of the Cardiovascular Health Study ( J Vasc Surg. 2002;36:443–51).

9. RAS is common in patients with vascular disease Prevalence of RAS Proven MI 12 % Undergoing cardiac catheterization 6-19% Lower extremity PVD 22-59 % Predictors of RAS in patients undergoing cardiac catheterization CAD; Age; PVD; serum creatinine ; hypertension

10. 3 year mortality 26% in patients treated with stents (Circulation 1998;98:642-647) 28% in patients managed medically (Mayo Clin Proc 2000;75:437) 4 year mortality 43% in patients with RAS discovered incidentally at cardiac catheterization (Kidney International 2001;60:1490-1497) 35% in patients with RAS discovered incidentally at cardiac catheterization (JASN 1998;9:252-256) 26% in a multi- center study of patients undergoing percutaneous renal revascularization (Circulation 1998;98:642-647) 5 year mortality 33% in a single- center study of patients undergoing percutaneous renal artery revascularization (Catheter Cardiovasc Interv . 2007;69:1037)

11. Clinical Pointers: Progression of Atherosclerotic RAS 48% of patients with <60% stenosis progress to >60 % over 3 years 39 % patients with >75% stenosis progress to complete occlusion over 3 years Average progression ~7% per year P rogression of RAS and loss of renal function occur independently of blood pressure control D. Lao et al.

12. 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 RA 5.5% < 60 % stenosis 11.7% > 60 % stenosis 20.8% Risk of atrophy increased by systolic hypertension (> 180mm Hg) and a high peak systolic velocity Caps et al, Kidney International, 1998

13. Clinical manifestations

14. Unilateral RAS results in vasoconstrictor-mediated HTN, while bilateral or solitary kidney RAS results in HTN with volume overload . CARDIAC DESTABILIZATION SYNDROMES . Uncontrolled HTN and volume retention associated with ARAS play an important role in the destabilization of patients with ACS or CHF. The Pickering syndrome , sudden onset , “flash,” pulmonary edema , is a commonly recognized destabilization syndrome resulting from ARAS. The presence of these syndromes should prompt an investigation for RAS . ISCHEMIC NEPHROPATHY . If the cause of CKD is ischemic nephropathy, this is potentially reversible. Some studies suggest that as many as 12% of patients with end-stage renal disease have CKD attributable to progressive ischemic nephropathy from ARAS. Atrophy of the kidney occurs as a consequence of the progression of ARAS . In patients with CKD and severe ARAS, renal artery stenting is most beneficial in those with a more rapid rate of decline.

15. Advanced nephropathy that is not likely to benefit from revascularization has been described by Proteinuria >1 g/day, Kidney pole-to-pole length of <7 cm, or H emodialysis for >3 months

16. Who should we screen?

17. clue Onset of hypertension <age 30 years Onset of severe hypertension after the age of 55 years Malignant or refractory hypertension Unexplained renal atrophy or size discrepancy of >1.5 cm between kidneys Worsening renal function upon initiation of ACE-I/ARB therapy Sudden, unexplained pulmonary edema (especially in azotemic patients). Unexplained progressive renal insufficiency Presence of multivessel coronary artery disease or peripheral arterial disease Unexplained congestive heart failure or refractory angina Abdominal bruit ( more than 75 % of patients)

18. Diagnostic Test (currently recommended) Renal artery duplex imaging C omputed tomography Magnetic resonance angiography Conventional Angiography

19. Noninvasive diagnostic modalities Renal Artery Ultrasound Safe, inexpensive and widely available, Images of the renal arteries as well as blood flow velocity and pressure waveforms, Information regarding kidney size and renal resistive index Body habitus dependent Operator dependent May miss accessory arteries Allows post intervention surveillance

20. Renal artery/aortic Peak Systolic velocity ratio > 3.5 ( Sn 84%, Sp 92 %) for 60% stenosis Renal artery Peak Systolic Velocity (PSV) >200 cm/s ( Sn and Sp ~98 %) for > 50% stenosis. End Diastolic Velocity (EDV) >150 cm/s (RAS >80%) Significant discrepancy in kidney size Acceleration time: (time period between the onset of systolic upstroke and the initial peak velocity ( compliance peak )). Normal <100 ms (usually 40–50 ms )→ if >100 ms associated with RAS 60 % Renal resistive index (RRI = 1 − EDV/PSV): ( Normal < 0.7, nephrosclerosis > 0.7)

21. Duplex Assessment of RAS Duplex Criteria Stenosis 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

22. The renal resistive index (RI) is a commonly used measure of resistance to arterial flow within the renal vascular bed. An elevated RI is considered to be an indicator of nephrosclerosis and intrinsic kidney disease Despite initial studies suggesting lack of benefit of RAS therapy with RRI >0.8, M ore recent studies suggest that a significant response in renal function may be obtained despite an abnormal resistive index, but this response is more blunted . Therefore , RRI should not use as the sole decision maker to revascularize or not.

23. Predicting outcomes of the revascularization Resistive Index: 1-end-diastolic velocity/peak systolic velocity 6000 Patients with HTN/ and clinical suspicion, screened for RVH., 131 had RAS, . Patients with resistive index >0.8 80% had decline in renal function 50% dialysis dependant Only 1 patient had > 10mmhg reduction in BP. Patients with RI < 0.8 94 % had significant reduction in BP. 3% had decline in renal function Radermacher , J, et al. Use of Doppler ultrasonography to predict the outcome of therapy for renal-artery stenosis. N Engl J Med 2001 ; 344:410.

24. Outcomes Predicted By RRI Radermacher et al NEJM. 2001;344:2244-49

25. Computed Tomography Angiography Excellent images can be obtained Sensitivity >91 %; Specificity 85–99 % Image interpretation may be difficult in heavily calcified arteries; I nvolves the use of ionizing radiation and iodinated contrast

26. Magnetic Resonance Angiography Identifies accessory renal arteries Provides additional anatomical information No radiation No nephrotoxic contrast Sensitivity 90–100 %; Specificity 76–94 % MRA is preferred in heavily calcified arteries, which can be a greater challenge for CTA. Looses accuracy in distal segments (FMD ) Gadolinium-based contrast associated with nephrogenic systemic fibrosis in patients with moderate-to- endstage renal failure;

27. Invasive Stenosis Assesment A n angiographic ARAS >70% diameter stenosis is severe or significant , and diameter stenoses of 50% to 70% are considered moderately severe, of uncertain hemodynamic significance . For moderately severe stenoses , confirmation of the hemodynamic severity of the RAS is recommended prior to stenting . A resting or hyperemic translesional systolic gradient of > 20 mm Hg, a resting or hyperemic mean translesional gradient of >10 mm Hg, or a renal fractional flow reserve (RFFR) <0.8 will confirm hemodynamically severe ARAS . The translesional pressure gradient should be measured using a nonobstructive catheter or a 0.014-inch pressure wire. Hyperemia may be induced with an intrarenal bolus of papaverine at a dose of 40 mg or an intrarenal bolus of 50 mg/kg dopamine

28. Optimal Medical Treatment Antihypertensive LDL to goal Currently <100 (or 70) mg/dl Diabetes Management HbA1c to target (<7%) Smoking Cessation Anti-platelet therapy (aspirin +/- clopidogrel )

29. 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 I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III Angiotensin receptor blockers are effective medications for treatment of hypertension associated with unilateral RAS. ACC/AHA Guidelines ACC/AHA Guidelines

30. 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. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III ACC/AHA Guidelines ACC/AHA Guidelines

31. 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. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III ACC/AHA Guidelines ACC/AHA Guidelines

32. Renal Artery Stenting Effect and Indication

33. Goal of Renal Stenting Clinical goals 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)

34. ARAS is often due to bulky aorto-ostial plaque, balloon angioplasty alone is frequently ineffective because of the recoil associated with these bulky plaques , making renal artery stenting the preferred method of treatment.

35. MINIMIZING COMPLICATIONS The complication rate approaches 2%. T he most common complications related to femoral access (hematoma , pseudoaneurysm , arteriovenous fistula), A theroembolism , R etroperitoneal hematoma, R enal artery rupture, A ortic and renal artery dissection, C ontrast nephropathy, Renal infarction, and Death

36. Technical issues one should consider in order to reduce complications include R adial artery vascular access, E mbolic protection devices (EPDs ), Catheter-in-catheter technique, No- touch technique , Stent sizing with intravascular ultrasound (IVUS ), Hydration before and after angiography is performed

37. No-touch technique 0.035-inch , J-tip guidewire is advanced in the abdominal aorta superior to the renal arteries. Over this wire, the guide catheter is advanced in proximity to the renal artery

38. 0.035 inch wire is then retracted to the soft portion of the wire S o that the guide catheter begins to assume its shape and approach the ostium of the renal artery. The J-shaped portion of the wire is left outside to guide against the aortic wall

39. G uiding catheter is gently rotated and aligned with the renal ostium , With the J wire preventing guiding catheter intubation into the renal artery. From this position, a 0.014-inch wire is advanced through the guide and into the distal renal artery

40. 0.035-inch J wire is then removed, and Guiding is advanced over the 0.014 inch wire to engage the renal artery.

41. No Touch”” Techniique

42. Most renal ostial lesions originate from the aortic atherosclerosis. Flank pain should be closely monitored because it indicates stretching of the adventitia. If detected, higher-pressure inflations should be avoided It is critically important to avoid over dilation as aorta or renal artery dissection is a dreaded consequence The size of the balloon-mounted stent should be sized according to the normal renal caliber and not the adjacent post stenotic dilatation that is often present distal to a hemodynamically significant stenosis.

43. Post balloon angioplasty angiogram is performed to document the procedural result. Radiographic evidence of either residual stenosis or renal artery dissection constitutes suboptimal angioplasty results, which warrants an immediate renal artery stent placement. A therosclerotic involvement of the renal artery usually involves the vessel orifice, which typically requires a balloon-expandable stent placement . Most atherosclerotic renal artery lesions demonstrate significant recoil after balloon angioplasty and therefore require stent placement Stent is deployed by expanding the angioplasty balloon to its designated inflation pressure, which is typically less than 8 atm

44. For ostial lesions, it is important to deploy the stent with the proximal segment protruding 1–2 mm inside the aorta and to Flare the extending portion with a compliant balloon Efficacy of drug-eluting stents (DES) is unknown Use of DES in the initial treatment does not recommended at this time. For in-stent restenosis, DES can be considered depending on the size of the renal artery.

45. Completion angiogram should be done to assess proper coverage of the renal ostium by the stent, the main renal artery, and its branches for signs of dissection or spasm and the renal parenchymal blush to exclude evidence of atheroembolization .

46. Follow up and Screening After RAS Stenting Dual antiplatelet therapy with aspirin (325 or 162 mg daily ) and clopidogrel (75 mg daily) for at least 30 days; Then monotherapy with aspirin (81 mg daily) chronically . Surveillance is not standardized . Renal ultrasound to be performed within 1–2 weeks after RAS stenting to establish a new baseline, F ollowed by US in 6- and 12-months. CT and MRI are less useful given the artifact seen in the presence of the stent. Regular monitoring of blood pressure and renal function.

47. Technical success:98-100% Long term patency rate 80%-95% Complications: Mortality 1-3% Major complications: 3-5% Minor complications 10-20%

48. complications Most complications are related to arterial access. I nclude groin hematomas, retroperitoneal hemorrhage , pseudoaneurysm , arteriovenous fistula , and infection. Atheroembolism into the renal or peripheral vascular bed : cholesterol embolization Dissection of renal artery or the wall of the aorta Acute or delayed thrombosis Rupture of renal artery Renal perforation

49. Renal Artery Embolization 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

50. Arteriogram demonstrating renal artery rupture and extravasation of contrast after balloon angioplasty

51. Effect on Renal Function Lim and Rosenfield , Curr Int Cardiol 2000,2:130-139.

52. Results of revascularization for ischemic nephropathy 33 patients with bilateral RAS or RAS in solitary kidney. Follow up: 20±11 months. Significant improvement in 72%; mild improvement in 28%. Preservation of renal size in all patients . Watson et al. Circulation 2000

53. Signs that a patient with ischemic nephropathy will benefit from revascularization Normal distal arterioles. Bilateral disease. Recent onset of renal insufficiency. Resistive Index (Doppler sonography ) <80 Extremely limited renal function ( cr >2.5 mg/dl) Uder M, Huke U CVIR 2005

54. Clinical outcome of renal artery stent placement

55. Effect on Hypertension

56. Why renal function may deteriorate after revascularization Contrast nephropathy. Cholesterol embolization. Exposure of diseased glomeruli to high blood pressure.

57. ASTRAL study 806 patients were randomized to either medical therapy alone (403 patients) or medical therapy and revascularization, PTA and/or stent (403 patients) The authors concluded that stenting is not superior to medical therapy. This study has been criticized because of a lot of limitations ,

58. Patients were excluded if their physicians thought that they might not benefit from intervention . 40 % of patients had a stenosis <70% unlikely to be hemodynamically significant Pressure gradient was never measured in any patient. Some patients had a renal length of 6 cm, which is generally considered as a contraindication for a revascularization 40% of the stented groups were unlikely to have benefited even from a successful intervention without complications, since they probably did not have the disease ‘‘ ischemic nephropathy ’’ in the first place Higher complication rate and inexperienced operator

59. Coral trial It was a larger trial of 947 participants having hypertension and RAS >80% or more than 60% with a pressure gradient of 20 mmHg. It compared renal artery stenting with medical therapy versus medical therapy alone. Optimal medical therapy was given in both groups. The primary endpoints were major cardiovascular or renal events (cardiovascular or renal death, MI, CHF, stroke, progressive renal insufficiency and need of renal replacement therapy). Secondary endpoints were all cause mortality and individual components of primary endpoint . The authors of the trial concluded that there was no difference in the cardiovascular and renal events or all cause mortality seen in the two groups.

60. CORAL although more robust in its patient selection, Still included patients with stable disease and has similarly been criticised as proving only that treating non-significant lesions does not significantly change outcomes The mean % stenosis: ( 67.3±114 %) The mean blood pressure: 149.9±23.2 mmHg

61. The CORAL trial as well as the ASTRAL trial demonstrated that in patients with moderate ARAS (50% to 70% diameter stenosis) and unconfirmed hemodynamic severity of RAS and HTN, there was no benefit of revascularization over GDMT alone. In a meta-analysis of 678 patients, the renal artery stenting procedure S uccess rate was 98%, Clinical improvement in HTN was only about 70 %, and I mprovement in renal function occurred in 30% of patients, with stabilization in 38%

62. Rationale for renal angioplasty stenting patient selection For good result after renal angioplasty stenting Good patient/lesion selection is mandatory before deciding which treatment to propose Peak systolic gradient ≥20 mmHg or a mean pressure gradient of 10 mmHg considered as hemodynamically significant Mean gradient > 20 mmHg after Dopamine is highly predictive of blood pressure improvement . A ratio of aortic pressure/ poststenotic pressure <0.90 is highly predictive of renovascular hypertension and blood pressure improvement .

63. Intravascular ultrasound, fractional flow reserve can also help to determine the severity of the stenosis Biomarkers: Renin, Brain Natriuretic Peptides . A ratio between the two kidneys, or the renal vein renin ratio (RVRR), of greater than 1.5 is indicative of functionally important renovascular hypertension , and it also predicts a favorable response from renovascular hypertension.

64. 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.

65. 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.

66. 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

67. Conclusions With modern equipment and skilled operators , renal artery stenting can be performed with high technical success (> 98%) and low restenosis (15-20 %) Incidental RAS is not an indication for revascularization. Following successful renal stenting there is slowing of deterioration of renal function and prevention of renal atrophy

68. Conclusions HTN is rarely cured (<10%-15%) in patients with atherosclerotic RAS The majority (>50%) will have some benefit with regards to HTN control and/or decreased anti-hypertensive drugs following renal stenting Revascularization is indicated in hypertensive patients with RAS if renal mass loss or renal function decline is observed during hypertensive treatment.

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