1. Management of Renal Artery Stenosis Kent MacKenzie, MD Division of Vascular Surgery McGill University Montreal, Quebec

2. Disclosures None

4. Atherosclerotic RAS Often orificial/ostial Associated aortic atherosclerosis Associated atherosclerosis elsewhere – Coronary – Carotid – Peripheral Fibrointimal Hyperplasia (FMD)

5. Atherosclerotic RAS Clinical Consequences – Hypertension – Ischemic nephropathy – Chronic renal failure – Dialysis

6. Hypertension

7. 1.Picture Renin-AII-Ald

8. Angiotensin II Vasoconstriction Sodium Retention Aldosterone Release

9. Sustained HTN Adaptive changes  PVR Heart Arteries Endothelial dysfunction  Nitrous oxide

10. The presence of hypertension is considered a prerequisite for renal artery intervention.

11. Diagnosis of RAS Hemodynamically significant lesion in renal artery in a patient with HPTN – Pressure gradient Diagnosis depends on identifying: – a pressure gradient – surrogate of a pressure gradient Functional surrogate Imaging surrogate

12. Functional Studies Intravenous Pyelography Differential Renal Function Studies Plasma Renin Activity Simulated Plasma Renin Activity Renal Vein Renin Catpopril Renal Scintography

13. Functional Studies

16. Functional Studies - Screening

17. Imaging Diagnosis Imaging surrogates for hemodynamic RAS – Duplex ultrasound – CT – MRA – Angiography

18. CT Angio – Minimally invasive – Calcification artifact

19. MRA – NSF – ?overestimates – experience

20. Duplex Ultrasound – PSV criteria – PSV RA/Aorta ratios Picture

21. Angiography – ? Smaller contrast load – Allows intervention

22. Imaging Diagnosis of RAS

23. In Practice High likelihood of RAS Good clinical indications for intervention – Duplex ultrasound – Ad-hoc Diagnostic +/- Therapeutic renal arteriography

24. Indications for Revascularization The presence of hypertension is considered a prerequisite for renal artery intervention.

25. Revascularization Potential Indications for renal revascularization – Incidental, asymptomatic RAS with need for aortic reconstruction – RAS with renal dysfunction alone – RAS with hypertension – RAS with hyperpertension and renal dysfunction – RAS with angina – RAS with recurrent flash pulmonary edema Chronic HPTN issues Acute HPTN issues

26. Revascularization with aortic surgery (prophylactic) 69 y.o. patient requires: – Open AAA repair – Endo AAA repair – Aortofemoral bypass for occlusive dx. Incidental imaging finding of severe RAS No severe HPTN at diagnosis

27. Revascularization with aortic surgery (prophylactic) 100 hypothetical patients with unsuspected RAS who will undergo aortic surgery – 44% (44 patients) lesion progression and RVH 36% (16 patients) may develop preventable reduction in renal function 66% (11 patients) will demonstrate restored function with delayed renal treatment Hansen KJ et al

28. Revascularization with aortic surgery (prophylactic) Therefore only 5 patients (5%) will gain a unique benefit from prophylactic renal artery repair Risk of adverse event with combined aortic/renal revasc. – 5-6% mortality in the best hands – 3-4% late failure of operative repair Therefore, prophylactic renal revasc. will potentially result in benefit in 5% of patients yet an adverse outcome in 10% Hansen KJ et al

29. Revascularization with aortic surgery (prophylactic) Prophylactic renal revascularization alone or in conjunction with aortic reconstruction is therefore not indicated – Surgical reconstruction – Catheter-based reconstruction Hansen KJ et al

30. Renal Insufficiency and RAS The absence of hypertension in a patient with RAS and excretory dysfunction suggests the presence of severe parenchymal disease Without HPTN, response to revascularization is poor

31. RAS and Hypertension alone Treatment is empiric Expectation of clinical improvement is less Unilateral vs. Bilateral RAS Hypertension response is poorly predictable

32. Accumulated experience has resulted in a paradigm shift in approach to selecting patients for intervention Surgical literaturePTA RAS and severe HPTN as a pre-intervention predictor of response Changes in renal function post-intervention being the short-term outcome Improvements in all-cause cardiovascular outcomes being the outcome of interest in trials evaluating RA intervention Hypertension with Renal Insufficiency

33. All patients

34. Hypertension with Renal Insufficiency

36. Treatment of hemodynamically significant RAS in a patient with: – Hypertension (severe) – Rapidly progressive decline in renal function – Salvageable renal mass Surgical literature suggests expectation of improved BP control and reduction in rate of functional loss Hypertension with Renal Insufficiency

37. RAS with angina or pulm edema Acute myocardial strain Acute episodes of severe hypertension Multiple case-series suggesting significant stabilzation of cardiac status after renal revascularization

38. Surgical Revascularization – Renal/aortic endarterectomy – Renal artery bypass Direct – Aortorenal bypass, iliorenal bypass – Renal artery reimplantation Indirect – Hepatorenal bypass – Splenorenal bypass – Mesorenal bypass Options for Intervention

39. Surgical Revascularization – Ex-vivo reconstruction To be considered in: – Solitary kidney – Complex renal artery branch reconstructions Options for Intervention

40. Percutaneous Treatment – Renal artery angioplasty – Renal artery angioplasty with provisional/selective stenting – Renal artery stenting Options for Intervention

41. No controlled studies comparing angioplasty vs. stenting Limited data comparing angioplasty/stenting to surgical revascularization No strong evidence demonstrating superiority of surgical revascularization over medical therapy No strong evidence demonstrating superiority of renal angioplasty/stenting over medical therapy Uncontrolled, non-randomized data supports the use of renal revascularization in high-risk groups

42. Side-by-side comparison of large surgical series and renal angioplasty series suggests better durability and improvements in renal insufficiency in surgical patients Comes at the cost of higher peri-procedural morbidity and mortality So percutaneous treatments selected in most patients other than those with need for aortic reconstruction or with contraindications for PTA

43. Randomized Trials Percutaneous Renal Artery Intervention

45. EMMA Trial, 1998 Unilateral atherosclerotic RAS Normal renal function 59 patients randomized Primary outcomes – Ambulatory blood pressure (ABP) Secondary outcomes – Treatment score – Complications

46. No difference in ABP But lower Treatment Score (fewer meds) in angioplasty group Higher procedural complication in angioplasty group (26% vs. 8%) Criticisms: – 1/3 eligible screened patients not enrolled because of patient or physician preference for angioplasty – Protocol called for antihypertensives in angioplasty group if BP control ‘not optimal’ Study design biased to not demonstrate primary outcome

48. Scottish/Newcastle study, 1998 Atherosclerotic uni- or bilat- RAS 135 patients eligible – Only 54 randomized – Non-randomized patients included for analysis Primary endpoints – Mean BP and serum creatinine 4 weeks and 6 months

49. Mean BP improved in medical and intervention arms during study period Mean BP after angioplasty improved only in the bilateral, randomized group Reduced hypertensive medication usage from 2.8 to 2.3 drugs in angioplasty groups No differences in renal function between groups

51. DUTCH renal angioplasty trial, 2000 106 patients with atherosclerotic RAS randomized Inclusion: – RAS >50% Diast. BP >95 mm Hg Worsening Creat on ACE inhibitor Primary Endpoints – Systolic and diastolic BP at 3 and 12 months Secondary Endpoints – Number of antihypertensive medications

52. RESULTS Blood pressure no different between groups Number of drugs in angioplasty group diminished (1.9 vs. 2.5) Criticisms: – Study design aimed for diastolic BP 95 mmHg Keeping drug numbers same might have led to improved BP in angioplasty group – 50% of patients in medical arm crossed over to angioplasty within 3 months of randomization

54. The Big Hurt

55. Patients where role of angioplasty was unclear BP was not severe (2 meds, mean 149/76) 40% patients had stenosis <70% Primary end-point decline in renal function 25% had normal renal function Only 12% had recent rapid decline in fcn.

56. Patients excluded were those most likely to gain benefit – Patients with: High-grade stenosis Poorly controlled hypertension Rapidly declining renal function Likely significant selection bias based on lack of equipoise to randomize patients

57. Also identified: – 27% of patient in the medical arm had an improvement of more than 10  mol/L during the period of study – This finding helps explain in part, the results of revascularization in uncontrolled, non-randomized cohort studies of renal angioplasty and surgical revascularization

58. The Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) Study: Rationale and Methods Timothy P. Murphy, MD, Christopher J. Cooper, MD, Lance D. Dworkin, MD, William L. Henrich, MD, John H. Rundback, MD, Alan H. Matsumoto, MD, Kenneth A. Jamerson, MD, Ralph B. D'Agostino, PhD

59. Still not in publication

61. Treatment Recommendations Medical Therapy

62. Treatment Recommendations Interventional Therapy

63. Treatment Recommendations Interventional Therapy

64. Treatment Recommendations Interventional Therapy

65. Treatment Recommendations Interventional Therapy

66. Treatment Recommendations Interventional Therapy

67. Treatment Recommendations Surgical Therapy

68. Treatment Recommendations Surgical Therapy

69. Summary Renal Revascularization Sound concept to treat a serious problem Basic science observations and observational studies support its role in treating RAS

70. Intervention – Severe bilateral RAS with severe hypertension – Selected unilateral severe RAS with severe hypertension – Severe RAS with renal dysfunction and HPTN If rapid progressive over short period – RAS with angina Associated with severe hypertension – RAS with CHF Coexistent hypertension, flash pulmonary edema

71. Angioplasty/Stent – First-line of intervention in the majority of cases Reduced procedural morbidity and mortality – Magnitude of benefit and durability – More evidence is required

72. Surgical Reconstruction Indication for renal revascularization and concomitant indication for aortic reconstruction – Aneurysm – Occlusive disease Renal occlusive disease involving aorta or renal artery bifurcation/branches Concomitant renal artery/branch aneurysm Young patient with good operative risk

73. Thank You