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

See also: Renal vein thrombosis

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 hypoperfusion leads to hyperactivation of the renin-angiotensin-aldosterone axis, causing hypertension. It is a cause of secondary hypertension. In the developed world, atheroma/arteriosclerosis is by far the commonest cause for renovascular disease. This normally develops at the the renal artery ostium on the luminal surface of the aorta/proximal renal artery. Atheroma may account for >90% of cases in white high-vascular-risk populations. In the Indian sub-continent and the Far East, Takayasu's arteritis is responsible for about 60% of cases.¹ The remainder are largely due to fibromuscular dysplasia of the renal artery which tends to affect the more distal portions of the renal artery. 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. The box below sets out the commoner causes of renal hypoperfusion.

It is certainly a common problem but 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 US it is estimated to account for 1–5% of cases of secondary hypertension in the general population, but as high as 30% in vascular high-risk groups, or up to 60% in those aged >70 years.²

A study of UK Type 2 diabetics with hypertension (a high-risk group for renovascular disease) and normal serum creatinine levels, utilising magnetic resonance angiography to detect the disease, found a prevalence of 17%. Ninety-five per cent of these patients had unilateral disease.³ The prevalence of angiographic renal artery stenosis in a group of UK patients undergoing angiography for suspected peripheral vascular disease was 36%.⁴

Risk Factors⁵

• Hypertension. However, up to 35% of patients with renovascular disease may be normotensive.
• Advanced age. Much commoner in those aged 60–70 years with prevalence increasing in those aged >75 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 whites 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; 15% or more increase in serum creatinine following introduction of ACEi is strongly suggestive of renal artery stenosis.
• 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')

Examination

• Seek 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?
• It is worth checking for radiofemoral delay and checking BP in both arms to look for aortic coarctation/dissection.
• The peripheral and carotid pulses should be palpated and bruits listened for to detect evidence of generalised vascular disease, the presence of which greatly increases the likelihood that hypertension is due to renovascular disease.
• Ophthalmoscopy should be carried out to look for evidence of hypertensive retinopathy, indicating long-standing hypertension, or to reveal evidence of occult diabetes.
• 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.
• 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.
• Dipstick urine for glucose and protein (mild to moderate proteinuria is sometimes a feature).

• Essential primary hypertension
• Any other cause of renal impairment in those who present with this feature, 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)

Before commencing investigation that may be time-consuming, expensive or unlikely to influence future management decisions, assess overall risk factors and likelihood of renovascular disease. Consider the patient's suitability/wish for specific intervention (particularly in older patients). Consider the possibility of other causes of hypertension and/or renal impairment and how likely they are compared to renovascular disease. If unsure as how to proceed with investigation, take advice from a physician/renal specialist.

Patients with suspected renovascular disease should have their U&Es and plasma glucose checked and ideally have 24-hour urine analysis to assess creatinine clearance and give a true picture of renal function (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.

• Duplex ultrasound is recommended as a useful screening test in suspected renovascular disease.
• CT angiography is another useful screening test in those with no evidence of renal impairment.
• MRI angiography may be used as a screening test to detect renovascular disease.
• If there is a high clinical index of suspicion of renovascular disease that may be amenable to intervention, and the above screening test(s) are negative then catheter angiography should be considered to make the diagnosis.
• Captopril renal scintigraphy, selective renal vein renin measurements, plasma renin activity and the captopril test – measuring plasma renin activity after adminstration of captopril – are not useful screening tests but may be employed for specialist investigation to decide on optimal treatment.

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

• Optimise vascular risk profile through smoking cessation, diabetes control, statins, adequate anti-hypertensive therapy.
• Avoid or be very cautious in the use of ACEi and angiotensin-II receptor antagonists.⁷
• Avoid other potentially nephrotoxic medications where possible, or adjust dose as advised by formulary, eg NSAIDs and renally excreted drugs.
• Seek expert advice where BP cannot be controlled or vascular intervention would be considered.

• 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 ACEi and angiotensin-II receptor antagonists
• Refractory heart failure or episodic recurrent pulmonary oedema
• Refractory angina

Variable depending upon severity of lesions, whether unilateral or bilateral, co-morbidities, age and response to medical or surgical therapy. Angiographic studies of the condition's natural history have shown progression of stenosis in about half of patients, notable within 2 years in those cases that do progress. Deterioration to complete renal artery occlusion affected between 9 and 16% of patients, usually those with a high degree of stenosis to begin with. One study showed mild to moderate stenosis tends not to worsen over a follow-up period of 14 years. About 40% of patients with >75% stenosis progressed to complete occlusion over this period.⁵

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 ACEi and angiotensin-II receptor antagonists in these patients mean that they should be avoided or used with great caution, preferably with specialist advice.