General practitioners (GPs) in Singapore are well-placed to diagnose most cases of renal artery stenosis and manage renovascular hypertension through medical therapy. A subset of patients may benefit from shared care with a specialist, and other treatment options including angioplasty and revascularisation therapy. Find out how we can work closely together with GPs to provide the best care for patients.

INTRODUCTION

Renovascular disease is one of the most common potentially correctable causes of secondary hypertension and often leads to resistant hypertension.

Renovascular hypertension is a result of reduced renal perfusion from renal artery stenosis (RAS) and subsequent activation of the renin-angiotensin-aldosterone system (RAAS). RAS can progress and cause ischaemic nephropathy from a chronic reduction in glomerular filtration rate.

Most cases of renovascular hypertension are caused by atherosclerosis, followed by fibromuscular dysplasia (FMD).

PREVALENCE OF RENOVASCULAR HYPERTENSION

The incidence of renovascular hypertension varies by clinical setting. It accounts for less than 1% of mild-to-moderate elevations in blood pressure.1 Its prevalence is much higher in patients with acute, severe or refractory hypertension.2 This often occurs superimposed upon cases with pre-existing hypertension.

PATIENT PROFILE AND SYMPTOMS

Patient profiles

Cases caused by atherosclerosis
Atherosclerotic renovascular disease is more common in patients with pre-existing atherosclerotic conditions such as coronary or peripheral arterial disease, and usually involves the aortic orifice or the proximal main renal artery.

Risk factors for atherosclerotic disease are often present, such as hyperlipidaemia, cigarette smoking and an age of over 55 years.

Cases caused by fibromuscular dysplasia
In contrast to atherosclerosis, FMD usually occurs in young women (< 35 years of age) presenting with an abrupt onset of hypertension, and typically involves the distal main renal artery or the intrarenal branches.

Symptoms

Clinical features suggestive of renovascular disease are described in Table 1 below.

Clinical features suggestive of renovascular disease
1. Unexplained creatinine elevation and/or acute and persistent elevation in serum creatinine of at least 50%, after administration of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB)
​2. Moderate-to-severe hypertension in a patient with diffuse atherosclerosis, a unilateral small kidney or asymmetry in kidney size of > 1.5 cm that cannot be explained by another reason
​3. Moderate-to-severe hypertension in patients with recurrent episodes of flash pulmonary oedema
​4. Onset of hypertension with blood pressure > 160/100 mmHg after the age of 55 years
​5. Systolic or diastolic abdominal bruit

 Table 1

EVALUATION AND DIAGNOSIS

Routine testing for renovascular disease may not change its management as current available evidence suggests that medical therapy may be as beneficial as invasive procedures, especially for those with atherosclerotic renovascular disease.

However, renal artery imaging should always be considered in young patients with resistant hypertension, and if clinical suspicion for FMD is high.

Renal Doppler ultrasonography

Renal Doppler ultrasonography is a reasonable imaging modality as it is relatively inexpensive, non-invasive and does not involve administration of contrast.

Magnetic resonance or computed tomography angiography has higher diagnostic utility, but are potentially harmful in patients with advanced chronic kidney disease given the risk of contrast nephropathy and gadolinium-induced nephrogenic systemic fibrosis.

A stenosis > 75% in one or both renal arteries or > 50% with post-stenotic dilatation suggests the diagnosis.

Renal intra-arterial angiography

Renal intra-arterial angiography is the gold standard.

It can be considered if other non-invasive tests are negative, clinical suspicion is high, and for patients on whom a corrective procedure will be performed if renovascular disease is detected or progresses.

It is not recommended as a routine test due to adverse risks such as contrast nephropathy and cholesterol emboli. It should not be done for those who respond well to medical therapy or are less likely to benefit from revascularisation (e.g., patients with advanced chronic kidney disease).

TREATMENT OPTIONS BY GPs

Medical therapy

Medical therapy is the first-line treatment approach to atherosclerotic renovascular hypertension. This includes the correction of modifiable cardiovascular risk factors such as hypercholesterolaemia, smoking and obesity.

Often, multiple antihypertensives are required. The use of ACE inhibitors or ARBs is recommended to counteract the inappropriately overactive RAAS.

Kidney function should be checked two weeks after the addition of an ACE inhibitor or ARB to ensure that the serum creatinine does not increase, and the ACE inhibitor or ARB can be continued if there is a < 25% rise in the serum creatinine from baseline.

WHEN TO REFER FOR SPECIALIST CARE

GPs may be the main party involved in diagnosing renal artery stenosis.

Referral to specialist care may be considered for patients with RAS and the clinical features described in Table 2, where a multidisciplinary team consisting of a nephrologist, cardiologist and interventional radiologist can help with management. 

Clinical features indicating GP referral to specialist care

​1. A short duration (weeks or months) of blood pressure elevation prior to the diagnosis of renovascular disease (even if the blood pressure can be controlled with drug therapy)

​2. Intolerance to optimal medical therapy (e.g., a clinically significant rise in serum creatinine after initiation of ACE inhibitor or ARB)
​3. Progressive deterioration in renal function that is thought to be a consequence of bilateral renovascular disease
​4. Progressive deterioration in renal function that is thought to be a consequence of unilateral stenosis affecting a solitary functioning kidney
​5. Recurrent flash pulmonary oedema and/or refractory heart failure
​6. Suspected fibromuscular disease in a young person

Table 2

TREATMENT OPTIONS BY SPECIALISTS

Revascularisation therapy

Revascularisation therapy with percutaneous angioplasty with or without stenting of the renal artery is second-line therapy.

A recent meta-analysis of nine randomised controlled trials concluded that renal artery angioplasty did not confer additional benefits above optimal medical therapy in patients with atherosclerotic renovascular disease, except in cases of refractory hypertension.4

Candidates for revascularisation should be carefully selected (see Table 2 for indications to consider revascularisation).

Angioplasty

As the pathophysiology of FMD is different compared to that of atherosclerotic renovascular disease, angioplasty is a therapeutic option for such patients.

Studies have suggested that angioplasty alone may improve blood pressure and even cure hypertension. Surgery may be indicated in very selected patients who have complex anatomic lesions (e.g., multiple small renal arteries, failed previous endovascular treatment).

Arteriogram showing focal stenosis - SingHealth Duke-NUS Vascular Centre
Figure 1 Arteriogram showing a focal stenosis of the left renal artery with post-stenotic dilatation (indicated by the arrow)

Arteriogram after percutaneous angioplasty - SingHealth Duke-NUS Vascular Centre
Figure 2 Arteriogram after a percutaneous angioplasty has largely corrected the stenotic lesion in the right renal artery (indicated by the arrow)

SHARED CARE – THE GP'S ROLE IN TREATMENT

Pre-care

GPs in Singapore are well-placed to manage hypertension. A subset of patients with renovascular hypertension may require the multidisciplinary care that the SingHealth Duke-NUS Vascular Centre (SDVC) offers.

If a GP feels that their patients require a more comprehensive approach to managing this condition (see Table 2), they may refer them to the Centre for further management.

Ongoing care

The specialists in the SDVC welcome collaboration with the patients’ GPs to provide the best care possible. Patients may choose to continue to follow up with their GP for the management of other chronic medical conditions such as diabetes, hyperlipidaemia and obesity.

Post-care and shared care

We welcome the opportunity to co-manage patients with GPs, who remain central to their care. It is common for patients to see specialists and dietitians at the Centre, while continuing to follow up with their GPs for other chronic medical conditions.

THE SINGHEALTH DUKE-NUS VASCULAR CENTRE

The SDVC was established in February 2021 to bring together the strengths of healthcare professionals from different specialities across SingHealth institutions.

It aims to provide seamless and holistic care for patients with vascular diseases related to disorders of the arteries, veins and lymphatics, including renal artery stenosis.

The care for a vascular patient is often complex, and usually involves coordination by the primary clinician to ensure the patient’s care needs are met.

Many of these conditions can now be managed by minimally invasive endovascular procedures without the need for open surgery, and many of these techniques have become the standard of care. Several specialists including vascular surgeons, cardiac surgeons, interventional radiologists, interventional nephrologists and interventional cardiologists perform endovascular procedures to treat these conditions.

Our centre collaborates with researchers and educators from SingHealth institutions and Duke-NUS Medical School to deepen knowledge in the causes of vascular diseases, drive innovation to find better ways to diagnose and treat conditions, and ensure healthcare professionals have the skills they need to provide the best care for patients.

 

REFERENCES

  1. Dworkin LD, Cooper CJ. Clinical practice. Renal-artery stenosis. N Engl J Med. 2009 Nov 12;361(20):1972-8. doi: 10.1056/NEJMcp0809200. PMID: 19907044; PMCID: PMC4812436.
  2. Textor SC, Lerman L. Renovascular hypertension and ischemic nephropathy. Am J Hypertens. 2010 Nov;23(11):1159-69. doi: 10.1038/ajh.2010.174. Epub 2010 Sep 23. PMID: 20864945; PMCID: PMC3078640.
  3. Chen Y, Pan H, Luo G, Li P, Dai X. Use of percutaneous transluminal renal angioplasty in atherosclerotic renal artery stenosis: a systematic review and meta-analysis. J Int Med Res. 2021 Jan;49(1):300060520983585. doi: 10.1177/0300060520983585. PMID: 33478308; PMCID: PMC7841243.

 

Dr Pang Suh Chien is a Consultant at the Department of Renal Medicine, Singapore General Hospital with an interest in interventional nephrology. She has been a care team member of SingHealth Duke-NUS Vascular Centre since February 2021.

GPs who would like more information about this topic, please contact Dr Pang at [email protected].

 

GPs can call the SingHealth Duke-NUS Vascular Centre for appointments at the following hotlines, or scan the QR code for more information:

Singapore General Hospital: 6326 6060
Changi General Hospital: 6788 3003
Sengkang General Hospital: 6930 6000
KK Women’s and Children’s Hospital: 6692 2984
National Cancer Centre Singapore: 6436 8288