Clinical review

Renal artery stenosis

Kevin McLaughlin,  Alan G Jardine,  Jon G Moss. 

Renal artery stenosis is becoming increasingly common because of atherosclerosis in an ageing population. Patients usually present with hypertension and varying degrees of renal impairment, although silent renal artery stenosis may be present in many patients with vascular disease. Despite improvements in diagnostic and interventional techniques, controversy remains over whether, when, and how to revascularise the kidneys of patients with renal artery stenosis.

	Pathophysiology

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The pathophysiology of unilateral renal artery stenosis provides a clear example of how hypertension develops. Narrowing of the renal artery, due to atherosclerosis or, rarely, fibromuscular dysplasia, leads to reduced renal perfusion. The consequent activation of the renin-angiotensin system causes hypertension (mediated by angiotensin II), hypokalaemia, and hyponatraemia (which are features of secondary hyperaldosteronism). Although these features may be reversed by correcting the stenosis, a classic presentation is uncommon, and hypertension is rarely cured in patients with atheromatous renal artery stenosis. In addition, it is now known that renal artery stenosis is underdiagnosed and may present as a spectrum of disease from secondary hypertension to end stage renal failure, reflecting variation in the underlying disease process. Thus, the presence of overt, or coincidental, renal artery stenosis usually reflects widespread vascular disease, with the associated implications for cardiovascular risk and patient survival.

View larger version (46K): [in this window] [in a new window]   Atheromatous lesions may affect different sized vessels within the kidney, and multiple lesions may exist. The site limits the potential for revascularisation; only lesions within the large vessels are amenable. The commonest site, at the ostium of the renal artery, is more effectively treated by stenting. Ulcerated atheromatous plaques may also generate cholesterol microemboli (particularly after vascular intervention)

	Clinical features

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Atheromatous renal artery stenosis typically occurs in male smokers aged over 50 years with coexistent vascular disease elsewhere. It is underdiagnosed and may present with a spectrum of clinical manifestations. Although conventionally thought of as a cause of hypertension, atheromatous renal artery stenosis is not commonly associated with mild to moderate hypertension. However, it is present in up to a third of patients with malignant or drug resistant hypertension. Renal artery stenosis is a cause of end stage renal failure, and patients commonly present with chronic renal failure (with or without hypertension). Typical patients have a bland urine sediment and non-nephrotic range proteinuria, although occasional patients may have heavy proteinuria with focal glomerulosclerosis on renal biopsy. Patients may also present with acute renal failure, particularly those with bilateral renal artery stenosis (or stenosis of a single functioning kidney) who are taking drugs that block the renin-angiotensin system.

Less common presentations include recurrent, rapid onset ("flash") pulmonary oedema, which is probably a consequence of fluid retention, and diastolic ventricular dysfunction, which often accompanies (bilateral) atheromatous renal artery stenosis. Biochemical abnormalities may also be present in patients with modest or no serious renal impairment. Patients with unilateral renal artery stenosis have raised circulating concentrations of renin and aldosterone and associated hypokalaemia; in contrast to patients with primary hyperaldosteronism, their plasma sodium concentration is normal or reduced. Patients with bilateral renal artery stenosis commonly have impaired renal function.

View larger version (150K): [in this window] [in a new window]   Angiogram of renal artery stenosis due to fibromuscular dysplasia of renal artery. Lesions typically affect the main renal artery, are beaded in appearance, and may have multiple stenoses

Clinical examination often shows bruits over major vessels, including the abdominal aorta (a feature of widespread atherosclerosis), although the classic finding of lateralising bruits over the renal arteries is uncommon.

	Diagnosis

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The main differential diagnoses of atheromatous renal artery stenosis in patients with hypertension and renal impairment are benign hypertensive nephrosclerosis and cholesterol microembolic disease. Differentiating between these conditions may be difficult, particularly as all three can occur simultaneously.

View larger version (147K): [in this window] [in a new window]   Gadolinium enhanced magnetic resonance angiogram showing a tight stenosis at the origin of the right renal artery. The left renal artery is normal

Angiography remains the standard test for diagnosing atheromatous renal artery stenosis and is widely available. However, it is not without risk and may worsen renal function. Non-invasive imaging techniques are beginning to replace conventional angiography. Although acceptable results have been reported by single enthusiastic centres, it remains to be seen whether these can be reproduced. Each has its own limitation. Doppler ultrasonography is very operator sensitive and is often impossible in obese patients. Spiral computed tomography requires the use of iodinated contrast media and radiation. Isotope renography (with or without captopril) has the advantage of providing information on renal function but is of little value in bilateral disease or when renal function is seriously impaired. Magnetic resonance angiography is the most promising imaging technique. It requires no contrast and permits reconstruction of the image in different planes. However, use of this technique is limited by lack of access to magnetic resonance imaging machines in the United Kingdom.

All the above non-invasive tests require variable degrees of patient cooperation, particularly the ability to hold a breath for up to 30 seconds for image acquisition. Moreover, none of the available imaging techniques identify the patients who will respond to revascularisation. The aim of investigation is to establish the diagnosis and whether revascularisation is possible or appropriate. In practice we use ultrasonography to define renal size and symmetry before proceeding to angiography to delineate the lesion. Magnetic resonance angiography is reserved for patients at high risk of angiographic complications.

	Prognosis

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The rate of progression of atheromatous renal artery stenosis is difficult to evaluate accurately, and reports from large tertiary referral centres are likely to be biased by case mix as the studies have followed selected cohorts. Moreover, follow up may be limited by the influence of concomitant vascular disease on survival. Most studies (over a variable follow up period) estimate the risk of radiological progression of atheromatous renal artery stenosis to be about 50%, and risk is dependent on initial severity of the lesion. The rate of occlusion of renal arteries with greater than 60% stenosis is about 5% a year.

View larger version (19K): [in this window] [in a new window]   Effect of coexistent renal artery stenosis on survival among patients having coronary angiography

Patients who have bilateral atheromatous renal artery stenosis with an occluded renal artery are three times more likely to reach end stage renal failure within two years than patients who have bilateral disease without occlusion (50% v 18%). The rate of loss of functional renal tissue (implied by loss of renal size of 1 cm at one year after diagnosis) is about three times higher for patients with bilateral disease than for those with unilateral disease (43% v 13%).

	Treatment

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Treatment of atheromatous renal artery stenosis must be tailored to the individual and should be undertaken in the expectation that revascularisation will prolong life. Hypertension in patients with renal artery stenosis can be controlled by drugs alone in almost 90% of cases. Angiotensin converting enzyme inhibitors reduce the glomerular filtration rate in about one third of patients with high grade bilateral atheromatous renal artery stenosis. Although this reduction is reversible in most cases, these drugs should be used with utmost caution.

Angioplasty is the traditional revascularisation procedure. Technical advances have revolutionised angioplasty, but few trials have examined its effects in renal artery stenosis. The available randomised controlled trials comparing drug treatment with angioplasty have shown only a modest reduction in blood pressure or antihypertensive drug requirements after angioplasty. Unlike treatment of fibromuscular dysplasia, cure of atheromatous renal artery stenosis by angioplasty alone is rare.

View larger version (21285K): [in this window] [in a new window]   Endovascular treatment. In this ostial lesion (left) there is no improvement after angioplasty because of elastic recoil (middle). An excellent morphological result is then achieved by stent placement (right)

Most atheromatous renal artery stenosis is due to aortic plaques encroaching on the ostium of the renal artery. Angioplasty is less than ideal in this situation because of the elastic recoil of the aortic plaques. The introduction of stents has helped overcome this problem. A recent randomised controlled trial comparing stent insertion to angioplasty alone in patients with ostial stenosis found a higher initial success rate (88% v 57%) and lower restenosis rate at six months (14% v 48%) in patients who had a stent inserted. Apart from expense there is little to argue against a policy of primary stenting for ostial renal artery stenosis. Although the patency rates from surgical bypass are excellent, surgery should probably be reserved for patients in whom stenting fails or who develop complications.

View larger version (195227K): [in this window] [in a new window]   Occluded renal artery before (left) and after (right) successful stenting. It is possible to revascularise an occluded renal artery provided there is distal reconstitution of the renal artery with collateral vessels maintaining viability. In this relatively unusual case, the patient required dialysis at presentation but became dialysis independent after stenting

	Benefits of revascularisation

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Renal function may improve greatly after vascular intervention, although it is difficult to identify which patients will benefit and the potential of the kidney distal to the stenosis to recover function. The available studies in patients with mild to moderate renal impairment show that renal function improves in 25% of patients, remains stable in 50%, and deteriorates in 25% after surgical revascularisation or stenting. Renal length 8 cm on ultrasonography and the presence of intact glomeruli on renal biopsy have been suggested as good prognostic markers but have not been formally studied. Patients in whom renal function deteriorates after vascular intervention have an extremely poor prognosis, with most requiring dialysis or dying within one year.

Although a modest improvement in blood pressure or a reduction in antihypertensive drug requirement may be the goal of revascularisation, renal protection may emerge as a more important factor. Animal studies have shown that renal tissue distal to renal artery stenosis undergoes irreversible ischaemic change, tubular atrophy, interstitial fibrosis, and glomerulosclerosis despite antihypertensive treatment. Although similar evidence is not available in humans, insertion of a stent in patients with renal artery stenosis slowed the rate of loss of renal function despite modest blood pressure benefits. A final reason to pursue revascularisation is the fact that patients with atheromatous renal artery stenosis have a worse prognosis than any other group on dialysis, with a median survival of 27 months, and prevention of progression to end stage renal failure may have greatest benefits in this group. The benefits of revascularisation, and the potential benefits of early intervention (for example, in patients with coincidental findings of renal artery stenosis) will need to be established by randomised controlled trials before the burden of additional procedures is placed on both radiologists and patients.

	Special cases

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Fibromuscular dysplasia is a much less common cause of renal artery stenosis. It principally occurs in young women, who present with unilateral disease, hypertension, and biochemical abnormalities. The lesions are graded by their distribution. In contrast to atheromatous renal artery stenosis, fibromuscular dysplasia is often cured by intervention, and often by angioplasty alone.

Patients with renal transplants have accelerated cardiovascular disease, one of the manifestations of which is the development of stenosis in the transplanted renal artery. This produces hypertension, fluid retention, and renal impairment similar to that found in patients with bilateral renal artery stenosis and is an indication for revascularisation.

	Treatment recommendations

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Recommending treatment for renal artery stenosis is difficult with the quality of the evidence available and the paucity of controlled trials. Surgical revascularisation is rarely indicated but may have a role in patients for whom angioplasty or stenting is not technically feasible or in patients with complex disease having abdominal vascular surgery. Nephrectomy (by minimally invasive surgery) may be considered in patients with unilateral disease whose blood pressure cannot be controlled because of a small or poorly functioning kidney.

Whatever recommendations we suggest, there will be disagreement. Firmly held, preconceived beliefs exist on the treatment of renal artery stenosis despite the fact that there have been few large outcome studies comparing treatment strategies. The ASTRAL (angioplasty and stent for renal artery lesions) study is a British randomised controlled trial that will compare angioplasty with and without stenting against drug treatment in 1000 patients with renal artery stenosis. Our future approach to the management of renal artery stenosis will depend on the conduct of relevant controlled trials.

	Acknowledgments

The picture of gadolinium enhanced magnetic resonance angiography was provided by D Wilcock, Leicester Royal Infirmary.

	Footnotes

Kevin McLaughlin is assistant professor of nephrology, University of Calgary, Canada; Alan G Jardine is senior lecturer and consultant nephrologist, department of medicine and therapeutics, Western Infirmary, Glasgow (a.g.jardine{at}clinmed.gla.ac.uk); and Jon G Moss is consultant interventional radiologist, Gartnavel General Hospital, Glasgow.

The ABC of arterial and venous disease is edited by Richard Donnelly, professor of vascular medicine, University of Nottingham and Southern Derbyshire Acute Hospitals NHS Trust (richard.donnelly{at}nottingham.ac.uk) and Nick J M London, professor of surgery, University of Leicester, Leicester (sms16{at}leicester.ac.uk). It will be published as a book later this year.