Renal Vascular Disease

Synonyms: Renovascular occlusive disease, atherosclerotic/atheromatous renal artery disease, atherosclerotic renovascular disease (ARVD), renal artery stenosis, renovascular hypertension, ischaemic nephropathy, renal artery fibromuscular hyperplasia

Renal vascular disease is the term given to the impairment of renal perfusion caused by disease affecting the arterial supply of the kidney(s). Renal vein thrombosis may cause a similar pattern of disease and is discussed in a separate article, Renal Vein Thrombosis.

Renal hypoperfusion leads to hyperactivation of the renin-angiotensin-aldosterone axis, causing hypertension.¹ Renal vascular disease is an important cause of secondary hypertension and chronic renal disease.

• In the developed world, atheroma/atherosclerosis is by far the commonest cause of renovascular disease. This normally develops at the renal artery ostium on the luminal surface of the aorta/proximal renal artery. The atheroma obstructs renal blood flow and leads to chronic renal ischaemia.² Atheroma may account for >90% of cases in white high-vascular-risk populations. Renal artery atheroma is commonly associated with more generalised atheroma and cerebral, cardiac and/or peripheral vascular disease.²
• In the Indian sub-continent and the Far East, Takayasu's arteritis is responsible for about 60% of cases.³
• The remainder of renovascular disease is largely due to fibromuscular dysplasia of the renal artery which tends to affect the more distal portions of the renal artery. Fibromuscular dysplasia is an angiopathy of uncertain aetiology that may affect the carotid and vertebral circulation, visceral arteries, and peripheral arteries.⁴ Some series estimate that fibromuscular dysplasia may make up to 30% of cases of renal artery stenosis in low-vascular-risk groups.
• Both atheroma and fibromuscular dysplasia cause unilateral renal artery stenosis in about 75% of cases.

Possible causes of renal hypoperfusion

• Renal artery atheroma/arteriosclerosis
• Fibromuscular dysplasia of the renal artery
• Prolonged hypotension or severe dehydration (usually transient but may cause permanent damage)
• Embolic renal disease
• Renal artery or aortic dissection
• Neurofibromatosis
• Renal arteriovenous malformation
• Takayasu's arteritis
• Other arteritides, e.g. polyarteritis nodosa
• Post-transplant renal artery stenosis
• Post-radiotherapy renal artery disease

• The exact prevalence is difficult to estimate as the condition may easily go undiagnosed among hypertensive patients, and there is an appreciable prevalence of undiagnosed hypertension in the population at large.
• In the United States it is estimated to account for 1–5% of cases of secondary hypertension in the general population, but as much as 30% in vascular high-risk groups, or up to 60% in those aged >70 years.¹
• A study of UK type 2 diabetics with hypertension (a high-risk group for renovascular disease) and normal serum creatinine levels using magnetic resonance angiography to detect the disease, a prevalence of 17% was found. Ninety-five per cent of these patients had unilateral disease.⁵
• The prevalence of angiographic renal artery stenosis in a group of UK patients undergoing angiography for suspected peripheral vascular disease was 36%.⁶
• Atherosclerotic disease is most common among older men.¹
• Fibromuscular disease is most common among women aged 30-40 years. It can also be a cause of secondary hypertension in children.⁴
• Renal artery stenosis is more common in Caucasian than Afro-Caribbean populations.¹

Risk factors²

• Hypertension (but up to 35% of patients with renovascular disease may be normotensive)
• Advanced age (much more common in those aged 60–70 years with prevalence increasing in those aged >70 years; one unselected post-mortem series showed a prevalence of 42% in those aged over 75)
• Evidence of renal impairment
• Evidence of peripheral vascular or cerebro/cardiovascular disease
• Diabetes mellitus
• Smoking
• Family history of cardiovascular disease or renovascular disease
• Hyperlipidaemia
• White racial background (approximately twice the prevalence in those with a white racial background compared to African Americans in a group of patients with severe hypertension)

The condition may present in a variety of ways and is usually asymptomatic. The following clinical scenarios are relatively common modes of presentation:

• Abrupt onset of hypertension in middle-aged or older patients
• Severe hypertension
• Hypertension resistant to standard medical therapy
• Hypertension developing in a patient with known peripheral-vascular/cerebrovascular/cardiovascular disease
• Hypertension developing in a patient with no family history of hypertension
• Biochemical or clinical evidence of renal impairment occurring during treatment with ACE inhibitors or angiotensin receptor blockers
• De novo renal impairment developing in a hypertensive or normotensive patient with vascular disease/risk factors
• De novo hypertension or renal impairment developing in an older patient who has been previously normotensive
• Hypertension with hypokalaemia (due to hyperaldosteronism) with no provoking medications or other identifiable cause (may be associated with metabolic acidosis)
• Decompensation of congestive cardiac failure in a hypertensive patient (may present with recurrent episodes of acute pulmonary oedema with no obvious precipitant – so-called 'flash pulmonary oedema')

Fibromuscular hyperplasia usually presents with renovascular hypertension or stroke. It can rarely present as subarachnoid haemorrhage, abdominal angina, or claudication of the legs or arms.⁴

• Look for evidence of vascular risk factors such as corneal arcus in younger patients, xanthomata, xanthelasmata, elevated blood pressure etc.
• Look at general appearance: is there any evidence of other causes of secondary hypertension such as Cushing's syndrome?
• Check for radiofemoral delay and also check blood pressure in both arms to look for aortic coarctation/dissection.
• Palpate peripheral and carotid pulses and auscultate for bruits to look for evidence of generalised vascular disease (the presence of which greatly increases the likelihood that hypertension is due to renovascular disease).
• An abdominal bruit, also heard over the flank, is a relatively common finding in patients with renovascular hypertension, being found in up to 50% of patients with the disease. However, up to 10% of patients with essential primary hypertension may have an abdominal bruit and innocent abdominal bruits are present in a minority of healthy younger patients, so it is not a pathognomonic sign.¹
• The presence of a systolic-diastolic bruit in a hypertensive patient is highly suggestive of renovascular disease.
• The cardiovascular system should be examined to detect any evidence of cardiac failure or to identify other causes of secondary hypertension.
• Perform ophthalmoscopy to look for evidence of hypertensive retinopathy, indicating long-standing hypertension, or to reveal evidence of occult diabetes.
• Dipstick urine for glucose and protein (mild to moderate proteinuria is sometimes a feature).

• Essential primary hypertension
• Any other cause of renal impairment, particularly glomerulonephritis
• Iatrogenic renal impairment
• Other causes of secondary hypertension
• Malignant primary or secondary hypertension
• Acute interstitial nephritis caused by medication, autoimmunity or hypersensitivity phenomenon following infection
• Nephrosclerosis
• Other causes of hypertension and albuminuria
• Collagen vascular diseases
• Arteritides (may cause renovascular disease or present similarly without affecting renal blood flow)

Urine and blood tests

• Urea, electrolytes and creatinine
• Glucose
• eGFR and/or 24-hour urine analysis to assess creatinine clearance (patients may have significantly reduced renal function but display urea and creatinine in the normal range)
• 24-hour urinary protein excretion and tests for microalbuminuria may aid in the decision-making process
• Urinalysis to exclude the presence of red blood cells/red blood cell casts which can be found in glomerulonephritis²
• Serology to exclude systemic lupus erythematosus or vasculitis if suspected (e.g. antinuclear antibodies, complement etc.)²
• Lipid profile, as renovascular disease is likely to be part of more extensive atherosclerotic disease

Other investigations

The choice of the best test for diagnosis of stenosis of the visceral arteries, whatever the aetiology, is controversial.^1,2,4

• Renal ultrasound is often performed in those with renal impairment but it is not diagnostic for renovascular disease. The diagnosis is suggested if there is a significant difference in kidney size (>1.5 cm).²
• Duplex renal ultrasound combines ultrasound and doppler techniques and can be a good diagnostic test. However, it is labour intensive and technician-dependent.²
• If there is a high clinical index of suspicion of renovascular disease that may be amenable to intervention, conventional angiography should be considered to make the diagnosis. However, there is a risk of complications such as arterial puncture and catheter-induced atheroembolism.² It has the advantage that endovascular therapy can be carried out at the same time.
• CT angiography uses intravenous injection of contrast material to allow images of the renal arteries. There is a risk of contrast associated nephropathy.²
• Magnetic resonance angiography allows direct visualisation of renal artery lesions and can be used to assess blood flow rate, glomerular filtration rate and renal perfusion rate.² However, it has only been validated for disease in the proximal renal arteries.²
• Radionuclide scanning following a dose of captopril can be helpful if fibromuscular disease is suspected in patients with normal renal function.²
• Selective renal vein renin measurements, plasma renin activity and the captopril test (measuring plasma renin activity after administration of captopril) were used in the past but are no longer thought to be useful screening tests.¹

Fibromuscular dysplasia is a pathological diagnosis. However, there are characteristic changes that can be seen on angiography in one form of fibromuscular dysplasia, medial fibroplasia. This is known as the 'string-of-beads appearance' caused by areas of relative stenoses or webs alternating with small fusiform or saccular aneurysms of the artery.⁴

• Neurofibromatosis
• Arteritides, particularly Takayasu's and polyarteritis nodosa
• Diabetes mellitus
• Fibromuscular dysplasia of the renal artery is possibly associated with α1-antitrypsin deficiency

Renal artery stenosis

General advice includes:

• Optimise vascular risk profile through smoking cessation, diabetes control, statins and adequate anti-hypertensive therapy.
• Avoid, or be very cautious in the use of, ACE inhibitors and angiotensin-II receptor antagonists.⁸
• Avoid other potentially nephrotoxic medications where possible, or adjust dose as advised by formulary, e.g. NSAIDs and renally excreted drugs.
• Seek expert advice if blood pressure cannot be controlled or vascular intervention is considered.

The management of renal artery stenosis can include:

• Medical management with drugs and vascular risk profile optimisation as above
• Vascular intervention techniques, including angioplasty ± stenting

Renal physicians are best placed to determine if or when vascular intervention is required in renal artery stenosis. This is an area that is controversial and is undergoing much research at present. It will depend on a number of factors including local facilities and expertise, coexistent disease, the degree of renal impairment and the rate of progression of renal disease.⁷

Angioplasty with stenting is generally used as the first line in vascular intervention. Open/endovascular surgery to reconstruct the stenosed artery and bypass procedures are also used. The current chronic kidney disease guidelines state that with regards to angioplasty, it is generally accepted that:⁷

• It is indicated in flash pulmonary oedema
• It should be considered in refractory/severe hypertension

Fibromuscular dysplasia

• For patients with fibromuscular disease, the results of percutaneous vascular intervention are generally superior to those of drug therapy alone.⁴
• Percutaneous transluminal angioplasty with balloon dilatation ± stenting is the treatment of choice for fibromuscular disease.⁴
• Vascular surgical reconstruction may also be used.

The evidence for best management

A recent systematic review of 55 relevant studies found that there were no studies directly comparing modern drug treatments for renal artery stenosis with modern angioplasty techniques, including stenting. The review concluded that there was insufficient evidence to clearly support one treatment approach over another for renal artery stenosis.⁹

A large multicentre trial testing treatment strategies for renal artery stenosis is currently underway in the United States comparing optimum medical therapy alone, to stenting with optimum medical therapy.¹⁰

Another trail, the ASTRAL (Angioplasty and Stent for Renal Artery Lesions) trial has also been designed to look at whether renal artery revascularisation with balloon angioplasty and/or stenting prevents progressive renal failure in those with renal artery stenosis. See "further reading" section below for link.

A Cochrane review looked at balloon angioplasty versus medical treatment for renal artery stenosis. It found that balloon angioplasty is superior to medical therapy in lowering blood pressure of people with renal artery stenosis and pharmacologically controlled blood pressure. However, where hypertension is refractory to medical therapy, there was weak evidence that balloon angioplasty lowers blood pressure more effectively than medical therapy. It concluded that randomised controlled trials are needed to compare the effect of balloon angioplasty and medical therapy on the preservation of renal function in the long term.¹¹

• End-organ damage from uncontrolled hypertension
• Progressive chronic renal failure
• Acute renal failure in rapidly advancing cases, or if intercurrent illness or other cause of renal insult
• Deterioration in renal function in patients taking ACE inhibitors and angiotensin-II receptor antagonists
• Refractory heart failure or episodic recurrent pulmonary oedema
• Refractory angina

Atherosclerotic renal artery stenosis is often present in people with atherosclerosis elsewhere and it is independently associated with an increased cardiovascular morbidity and mortality. The American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterisation, Council on Clinical Cardiology, and the Councils on Cardiovascular Radiology and Intervention and on Kidney in Cardiovascular Disease suggest screening for renal artery stenosis in those who are candidates for coronary revascularisation.¹²

• For renal artery stenosis, this is variable depending upon the severity of lesions, whether unilateral or bilateral, co-morbidities and coexisting atherosclerotic disease, age and response to medical or surgical therapy.
• One old study involving 169 patients with atherosclerotic and/or fibromuscular disease looked at progression of the disease over a 10 year period. Progression of atherosclerotic disease was seen in about 44%. Deterioration to complete renal artery occlusion affected 16% of patients with atherosclerotic disease. Progression was seen in 33% with fibromuscular disease.¹³

• Primary preventive strategies for atheromatous vascular disease.
• Secondary preventive strategies for atheromatous vascular disease in those with established renovascular disease or other vascular disease.
• The deleterious effects of ACE inhibitors and angiotensin-II receptor antagonists in these patients mean that they should be avoided or used with great caution, preferably with specialist advice.