• Information
  1. Introduction
  2. Atherosclerotic Disease
  3. Fibromusclar Dysplasia
  4. Diagnosis
  5. Treatment

A. Introduction

1. Most common cause of secondary hypertension (HTN)
2. Accounts for ~1% of cases of HTN in general population
3. Major causes of RAS
   1. Atherosclerotic Disease >90% of cases
   2. Fibromuscular Dysplasia (FMD) <10% of cases
4. Mechanism of HTN [2]
   1. Hypoperfusion of kidney leads to elevated renin and angiotensin II (AT2)
   2. AT2 is a potent vasoconstrictor
   3. AT2 also stimulates production of aldosterone from the adrenal gland
   4. Activation of renin-AT2 system increases oxidative stress (reactive oxygen species)
   5. Reactive oxygen species block nitric oxide induced endothelial dilation
   6. Thus, HTN, direct AT-2 effects, and nitric oxide reduction cause vascular dysfunction
5. Severe disease may cause substantial intrinsic kidney dysfunction

B. Atherosclerotic Disease

1. Renal Artery Atherosclerosis [3]
   1. Increasing cause of renal disease and HTN
   2. Usually involves ostium and proximal 1/3 of main renal artery
   3. Segmental and diffuse atherosclerosis may be seen in advanced disease
   4. Progressive disease occurs in ~50% of patients; <15% become totally occluded
   5. Renal atrophy develops in ~20% of patients with stenoses >60%
   6. Renal atrophy is due to hypoperfusion and ischemic nephropathy
2. Embolism
   1. Atheroembolic disease may be responsible for 5-10% of ARF in hospital
   2. Hypercoagulable states
   3. Diffuse atherosclerosis
3. Cholesterol Emboli Syndrome
   1. Fragements of cholesterol plaques break off and circulate
   2. Highly inflammatory, particularly in microvasculature, produce vasculitis-like reaction
   3. Dislodging atherosclerotic plaques particularly after mechanical instrumentation

C. Fibromusclar Dysplasia (FMD) [8]

1. Collection of vascular diseases of renal artery
2. Affects intima, media and/or adventitia
   1. ~90% of cases involve the media
   2. ~10% of cases involve intimal fibroplasia
   3. Adventitial (periarterial) hyperplasia is rare
3. Presentation
   1. Mainly affects women ages 15-50
   2. Usually presents as HTN in young persons, typically when media is involved
   3. Thrombosis and infarctions of kidney, gut, and/or liver when intima or adventita involved
   4. ~30% of cases have extracranial vascular or other vascular bed disease
   5. Unknown cause; cigarette smoking implicated
4. Usually affects distal 2/3 of renal artery and its branches
   1. Beaded, aneurysmal appearance in medial disease
   2. Intimal disease shows focal concentric stenosis with long, smooth narrowing
   3. Rarely leads to total occlusion, but progression occurs in ~37% of cases
5. Main symptom is HTN with renal dysfunction

D. Diagnosis

1. Overview [1]
   1. Noninvasive evaluation performed first
   2. If RAS present, nuclear imaging to estimate fractional flow to each kidney
   3. Unilateral with asymmetric flow or bilateral RAS should consider revascularization
   4. In patients with renal resistance index value at least 80, surgery or angioplasty will not improve outcome and medical treatment alone should be considered [7]
   5. Unilateral RAS with symmetric flow should be followed and treated medically
2. Assessment
   1. Renal function studies - blood urea nitrogen, creatinine, nuclear medicine
   2. Physiologic studies assessing renin-angiotensin system
   3. Perfusion studies - nuclear medicine studies, captopril renography
   4. Duplex Ultrasonography
   5. Magnetic Resonance Imaging (MRI) and MR Angiography (MRA)
   6. Computed Tomography (CT) angiography
   7. Digital subtraction (invasive) angiography (DSA) is gold standard [5]
3. Non-Invasive Imaging
   1. MRI and MRA are always preferred in elderly patients with HTN and possible RAS
   2. Gadolinium is not nephrotoxic
   3. CT angiography with IV contrast (nephrotoxic) may also be used
   4. Sensitivity of CT or MRA are 60% with ~90% specificity compared with DSA [5]
   5. MRA and CT angiography preferred in patients with possible RAS and HTN [6]
   6. MRA and CT angiography are superior to captopril-renal scans [6]
   7. Duplex ultrasonography can provide good images and quantity of renal blood flow
4. Invasive Evaluation
   1. Contrast enhanced digital subtraction angiography (DSA) goals:
   2. Confirm diagnosis and cause of RAS
   3. Evaluate extent of intrarenal vascular disease
   4. Determine the dimensions of the kidneys
   5. Identify associated aneurysmal or occlusive dsiseases of the aorta
   6. Low-osmolar contast material recommended, but it is nephrotoxic
   7. Intraarterial digital subtraction can help reduce contrast needed to 15-20mL (safe dose)
5. Response of Renin-Angiotensin System
   1. Captopril-renal scans are no longer generally used due to advent of MRA and CT
   2. In these tests, ACE-inhibitor induces marked reduction in renal blood flow

E. Treatment [12]

1. Underlying medical conditions should be stabilized / treated whenever possible
   1. Aggressive treatment of HTN should be pursued in all patients
   2. However, in general, restoration of blood flow to kidney is required for treatment
   3. Unclear if renal artery angioplasty with stenting is superior to aggressive medical therapy
   4. Renal artery angiogplasty with stenting is likely preferred in bilateral RAS [12]
2. Treatment of HTN
   1. HTN in patients with FMD usually responds to ACE inhibitors (ACE-I)
   2. Angiotensin II receptor antagonists (ARB) can be used in ACE-I intolerant patients
   3. HTN in patients with atherosclerosis nearly always requires combination therapy
   4. ACE-I or ARB + diuretic or other agent may be considered
   5. In these patients, calcium blockers or ß1-adrenergic blockers are recommended
   6. Severe RAS can lead to renal atrophy and treatment resistant HTN
   7. Renal artery stenting may improve BP better than combination drug therapy [12]
3. Invasive Treatment
   1. Percutaneous transluminal renal angioplasty (PTRA) with now usually with stenting
   2. Surgical bypass - highly invasive, usually last resort
   3. In patients with renal resistance index value at least 80, surgery or angioplasty will not improve outcome [7]
4. PTRA [8]
   1. Often effective for FMD or atherosclerotic RAS
   2. Clearly more effective than drug therapy for treating HTN associated with RAS [11,13]
   3. Balloon angioplasty likely reduces renal dysfunction compared with drug therapy alone [11] but this is not clear [13]
   4. PTRA can cause dissection or abrupt closure, as for coronary angioplasties
   5. Renal artery stenting - following failed angioplasty or for restenosis after angioplasty
   6. Consider PTRA in patients with poorly controlled HTN and renal atherosclerosis
   7. Usually performed with stenting, which reduces restenosis
5. Renal Artery Stenting [9,10]
   1. Vascular stent implantation is effective and safe in RAS
   2. Stenting is highly preferred for ostial renal artery occlusions [10]
   3. Also for failed angioplasty or for restenosis after angioplasty
6. Surgical Revascularization
   1. Has largely been replaced by ACE inhibitors and PTRA
   2. Most methods now use celiac or mesenteric - renal bypass (rather than aortic bypass)
   3. Early graft failure, usually due to graft thrombosis, occurs in ~5%
   4. Perioperative mortality ~5%
7. Nephrectomy [4]
   1. Renal atrophy can lead to treatment resistant HTN
   2. HTN urgency or emergency can occur
   3. Removal of an atrophic kidney can improve blood pressure control
   4. Removal of one atrophic kidney generally does not lead to loss of renal function

References

1. Safian RD and Textor SC. 2001. NEJM. 344(6):431
2. Higashi Y, Sasaki S, Nakagawa K, et al. 2002. NEJM. 346(25):1954
3. Abuelo JG. 1995. Ann Intern Med. 123(8):601
4. Kane GC, Textor SC, Schirger A, Garovic VD. 2003. Am J Med. 114(9):729
5. Vasbinder GBC, Nelemans PJ, Kessels AGH, et al. 2004. Ann Intern Med. 141(9):674
6. Vasbinder GBC, Nelemans PJ, Kessels AGH, et al. 2001. Ann Intern Med. 135(6):401
7. 12. Radermacher J, Chavan A, Bleck J, et al. 2001. NEJM. 344(6):410
8. Slovut DP and Olin JW. 2004. NEJM. 350(18):1862
9. Blum U, Krumme B, Flugel P, et al. 1997. NEJM. 336(7):459
10. Van de Ven PJG, Kaatee R, Beutler JJ, et al. 1999. Lancet. 353(9149):282
11. Van Jarrsveld BC, Krinjen P, Pieterman H, et al. 2000. NEJM. 342(14):1007
12. Balk E, Raman G, Chung M, et al. 2006. Ann Intern Med. 145(12):901
13. Nordmann AJ, Woo K, Parkes R, Logan AG. 2003. Am J Med. 114(1):44