Renal artery stenosis – how do we confirm the diagnosis?

12th December 2023, NIA Diagnostic Imaging

Renal artery stenosis

One of the standout diagnoses I remember from medical school is renal artery stenosis. In practice, it is usually someone else that makes that diagnosis. It is not that uncommon. We may hear an abdominal bruit in our general vascular screen. We might struggle to get our patient’s BP to target despite the 4^th or 5^th agent. It might be a faster than normal deterioration of eGFR despite an improvement in BP control. Or worse, there are signs of heart failure in a younger patient. We think, maybe, there is RAS. Apart from referring to a specialist, how can we confirm the suspicion?

What is renal artery stenosis?

Atherosclerotic renal artery stenosis (ARAS) has become the leading cause of end stage renal disease in the elderly (12). The role of diagnostic imaging such as a CT renal angiogram in such patients is critical to ensure early detection of renal artery pathology and to guide appropriate treatment (12). Renal artery stenosis (RAS) is narrowing of one or more of the renal arteries (3), which progressively decreases blood flow to the kidneys (13). It is a major source of renovascular hypertension, which is the underlying cause in approximately 75% of the cases of secondary hypertension (10, 13).

Atherosclerosis, a condition characterised by the buildup of plaque within the arteries, is the most prevalent aetiology of RAS where ARAS, which primarily involves the proximal renal artery, accounts for 60-90% of all cases of RAS (3). Patients with RAS typically present with clinical characteristics of secondary hypertension which include hypertension that is severe, abrupt in onset, or resistant to treatment (14).

ARAS is a progressive disorder that can lead to worsening ct renal angiogram stenosis where 51% of patients reported worsening stenosis 5 years after diagnosis (14). It is associated with renovascular hypertension, ischemic nephropathy (8), decreased kidney function, chronic kidney disease and end-stage renal disease (3). Individuals with RAS are at an increased risk of cardiovascular events, with high cardiovascular morbidity and mortality rates (6). It was found that greater than 25% of all patients who die of cardiovascular disease have some degree of RAS (10). Thus, it is imperative to promptly diagnose and commence treatment as appropriate to achieve optimal patient outcomes.

What is a CT renal angiogram?

The most common imaging studies utilised to evaluate the presence of RAS are duplex ultrasonography, computed tomographic angiography (CTA) and magnetic resonance angiography (MRA) (15).

A CT renal angiogram is a well-established minimally invasive diagnostic procedure for assessment of suspected RAS. This test involves the administration of intravenous contrast and acquiring detailed images to visualise the renal arteries, surrounding blood vessels and anatomical structures. This procedure is widely used for assessment of RAS because of its ease of availability, rapid acquisition, reproducibility, non-operator dependent and increased spatial resolution (12, 16). With high sensitivity (90% to 98%) and specificity (85% to 94%) in addition to aforementioned benefits (14), CT renal angiography is a valuable tool for diagnosing renal artery stenosis and can be performed in conjunction with a renal arterial doppler study.

Following the examination, the axial source images are analysed on the GE Advantage Workstation to perform vessel analysis, and obtain multiplanar reconstructions (MPR), maximum intensity projection (MIP) images and three-dimensional volume rendered images.

What information does a CT renal angiogram provide?

CT renal angiography plays a significant role in the diagnosis of RAS, and provides

extensive information regarding its presence and extent:

● Visualisation of anatomical structures including the renal arteries: The generated reconstructed images and vascular detailing provides high-resolution images, enabling excellent visualisation of the renal arteries (both main and accessory), surrounding blood vessels and anatomical structures. This allows detection of any abnormalities, including stenosis, plaques or blockages (15, 16).

● Assessment of stenosis severity: Advancements in computer post-processing techniques allow various morphological measures of the renal vessels to be obtained from the quantitative data (1). Stenosis analysis can be performed to demonstrate the degree of narrowing in the renal arteries and determine the severity which is important for treatment planning and prognostication.

● Identification of atherosclerosis: As atherosclerosis is a common cause of RAS, CT renal angiography can reveal the presence of atherosclerotic plaques within the renal arteries and aid in diagnosis, and understanding of underlying pathology (8).

● Three-dimensional imaging: By post-processing volumetric data, a three-dimensional reconstruction of the renal vasculature can be rendered, offering a means to visualise the vascular tree (15). This is valuable for a comprehensive understanding of vascular anatomy, aiding in visualising the extent and location of stenosis.

● Evaluation of kidney perfusion and function: CT renal angiography allows for assessment of renal perfusion (blood flow) to the kidneys, helping determine the potential impact of RAS on kidney function and the overall clinical significance of the stenosis.

● Preoperative planning: In cases where surgical intervention is considered, such as renal artery angioplasty or stent placement, CT renal angiography provides detailed anatomical information of the specific location and characteristic of the stenosis, aiding in preoperative planning.

How is renal artery stenosis treated?

Diagnosis of RAS using imaging techniques such as CT renal angiography, is useful for guiding clinical decision making and appropriate therapy. Optimal medical therapy remains the central approach to treatment and management of RAS (15). Medications such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) can be prescribed (14). Other medications may be prescribed to manage comorbidities such as hypertension, hyperlipidaemia and diabetes as these conditions contribute to decline in renal function and accelerate the disease progression in ARAS (8). In addition, statins or antiplatelet therapy may be recommended.

For newly diagnosed ARAS, lifestyle modifications with diet, regular exercise and smoking cessation (8), can help manage contributing factors such as high blood pressure and atherosclerosis. Other procedures to treat RAS include surgical and percutaneous revascularisation (6), however, invasive management may only be indicated in a few cases such as symptomatic patients with severe RAS who continue to have acute severe worsening of renal function (14).

The ASTRAL trial was designed to determine whether there was clinical benefit from revascularisation adjunct to optimal medical therapy compared to medical therapy alone (2). It was found that revascularisation therapy was not associated with any benefit to renal function, blood pressure, renal or cardiovascular events, or overall mortality when compared with patients treated with antihypertensive, antiplatelet, and cholesterol-lowering medication alone (2, 14). However, a limitation of the study was that patients with severe RAS (those presenting with kidney injury or pulmonary oedema) were unlikely to be included in the trial, as they were likely treated with revascularisation immediately (14).

Conclusion

It is evident that CT renal angiogram is a valuable tool for diagnosing renal artery stenosis, and crucial in assisting with treatment pathways to ensure optimal patient outcomes. This scan can be performed at NIA Radiology at both sites in Glenquarie and Ingleburn.

REFERENCES

1. Andersson, M., Jägervall, K., Eriksson, P., Persson, A., Granerus, G., Wang, C., & Smedby, Ö. (2015). How to measure renal artery stenosis – a retrospective comparison of morphological measurement approaches in relation to hemodynamic significance. BMC Medical Imaging, 15, 42. https://doi.org/10.1186/s12880-015-0086-8

2. ASTRAL Investigators, Wheatley, K., Ives, N., Gray, R., Kalra, P. A., Moss, J. G., Baigent, C., Carr, S., Chalmers, N., Eadington, D., Hamilton, G., Lipkin, G., Nicholson, A., & Scoble, J. (2009). Revascularization versus medical therapy for renal-artery stenosis. The New England Journal of Medicine, 361(20), 1953–1962. https://doi.org/10.1056/NEJMoa0905368

3. Bokhari, M. R., & Bokhari, S. R. A. (2023, July 17). Renal Artery Stenosis. StatPearls Publishing. Retrieved December 1, 2023, from https://www.ncbi.nlm.nih.gov/books/NBK430718/

4. Cho, E. S., Yu, J. S., Ahn, J. H., Kim, J. H., Chung, J. J., Lee, H. K., & Lee, K. H. (2012). CT angiography of the renal arteries: comparison of lower-tube-voltage CTA with moderate-concentration iodinated contrast material and conventional CTA. American Journal of Roentgenology, 199(1), 96–102. https://doi.org/10.2214/AJR.11.7450

5. de Mello Júnior, C. F., Araujo Neto, S. A., de Carvalho Junior, A. M., Rebouças, R. B., Negromonte, G. R., & de Oliveira, C. D. (2016). Multidetector computed tomography angiography of the renal arteries: normal anatomy and its variations. Radiologia Brasileira, 49(3), 190–195. https://doi.org/10.1590/0100-3984.2014.0048

6. Gallagher, A., & Mangos, G. (2023). Renal artery stenosis and hypertension: when to screen and how to treat. Medicine Today, 24(3), 23-29. https://medicinetoday.com.au/mt/2023/march/feature-article/renal-artery-stenosis-and -hypertension-when-screen-and-how-treat#:~:text=Renal%20artery%20stenosis%20(RAS)%20is,warrant%20further%20investigations%20for%20RAS

7. John Hopkins Medicine. (n.d.). Resistant hypertension. Retrieved December 1, 2023, from https://www.hopkinsmedicine.org/health/conditions-and-diseases/high-blood-pressure-hypertension/resistant-hypertension#:~:text=Resistant%20hypertension%20is%20 high%20blood,at%20their%20maximally%20tolerated%20doses

8. Manaktala, R., Tafur-Soto, J. D., & White, C. J. (2020). Renal artery stenosis in the patient with hypertension: Prevalence, impact and management. Integrated Blood Press Control, 20(13), 71-82. https://doi.org/10.2147/IBPC.S248579

9. Mayo Clinic. (n.d.). Renal artery stenosis [Image]. Retrieved December 1, 2023, from https://www.mayoclinic.org/diseases-conditions/renal-artery-stenosis/symptoms-causes/syc-20352777

10. Nair, R., & Vaqar, S. (May 22, 2023). Renovascular hypertension. StatPearls Publishing. Retrieved November 30, 2023, from https://www.ncbi.nlm.nih.gov/books/NBK551587/

11. Nejad, S. H., Azzam, O., & Schlaich, M. P. (2023). Resistant hypertension: an approach to management. Medicine Today, 24(8), 23-28. https://medicinetoday.com.au/mt/supplements/feature-article/resistant-hypertension-approach-management

12. Rountas, C., Vlychou, M., Vassiou, K., Liakopoulos, V., Kapsalaki, E., Koukoulis, G., Fezoulidis, I. V., & Stefanidis, I. (2007). Imaging modalities for renal artery stenosis in suspected renovascular hypertension: prospective intraindividual comparison of color Doppler US, CT angiography, GD-enhanced MR angiography, and digital substraction angiography. Renal Failure, 29(3), 295–302. https://doi.org/10.1080/08860220601166305

13. Saljoughian, M. (August 18, 2015). The role of renal artery stenosis. U.S. Pharmacist. Retrieved November 30, 2023, from https://www.uspharmacist.com/article/the-role-of-renal-artery-stenosis

14. Vipparla, N., Kichloo, A., Albosta, M. S., Aljadah, M., Wani, F., & Lone, N. (2020). Resistant hypertension secondary to severe renal artery stenosis with negative duplex ultrasound: a brief review of different diagnostic modalities. Journal of Investigative Medicine High Impact Case Reports, 8. ttps://doi.org/10.1177/2324709620914793

15. Weber, B. R., & Dieter, R. S. (2014). Renal artery stenosis: epidemiology and treatment. International Journal of Nephrology and Renovascular Disease, 7. https://doi.org/10.2147/IJNRD.S40175

16. Yadav, A., Buxi, T. B. S., Reddy, S., Ghuman, S. S., Rawat, K. S., & Gupta, S. (2015). CT abdominal angiography. Current Medicine Research and Practice, 5(1), 37-49. https://doi.org/10.1016/j.cmrp.2014.11.008

PFO Closure

Furlan AJ, Reisman M, Massaro J, et al. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med 2012; 366: 991–

A multicenter, randomized, open-label trial of closure with a percutaneous device, as compared with medical therapy alone, in patients between 18 and 60 years of age who presented with a cryptogenic stroke or transient ischemic attack (TIA) and had a patent foramen ovale. The primary end point was a composite of stroke or transient ischemic attack during 2 years of follow-up, death from any cause during the first 30 days, or death from neurologic causes between 31 days and 2 years.

Results:

Primary end point was 5.5% in the closure group as compared with 6.8% in the medical-therapy group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.45 to 1.35; P = 0.37)

Conclusion:

“In patients with cryptogenic stroke or TIA who had a patent foramen ovale, closure

with a device did not offer a greater benefit than medical therapy alone for the

prevention of recurrent stroke or TIA”

2 Saver JL, Carroll JD, Thaler DE, et al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med 2017; 377: 1022–

A multicenter, randomised, open-label trial ,randomly assigned patients 18 to 60 years of age who had a patent foramen ovale (PFO) and had had a cryptogenic ischemic stroke to undergo closure of the PFO (PFO closure group) or to receive medical therapy alone (aspirin, warfarin, clopidogrel, or aspirin combined with extended-release dipyridamole; medical-therapy group). The primary efficacy end point was a composite of recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomisation.

Results:

Recurrent ischemic stroke occurred in 18 patients in the PFO closure group and in 28 patients in the medical-therapy group, resulting in rates of 0.58 events per 100 patient-years and 1.07 events per 100 patient years, respectively (hazard ratio 0.55; 0.31 – 0.999; P = 0.046)

Conclusion:

“Among adults who had had a cryptogenic ischemic stroke, closure of a PFO was associated with a lower rate of recurrent ischemic strokes than medical therapy alone during extended follow-up.”

Meier B, Kalesan B, Mattle HP, et al. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med 2013; 368: 1083–

A prospective, multicenter, randomised, event-driven trial, randomly assigned patients to medical therapy alone (anti-platelet or warfarin therapy) or closure of the patent foramen ovale.

Results:

9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke (hazard ratio with closure, 0.49; 0.22 – 1.11; P = 0.08). The primary analysis of the intentionto- treat cohort showed a nominal 51% hazard rate reduction with closure, but the reduction did not reach significance.

Conclusions:

” …there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic ischaemic stroke.”

Sondergaard L, Kasner SE, Rhodes JF, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med 2017; 377: 1033–

Multinational trial involving patients with a PFO who had had a cryptogenic stroke, randomly assigned patients to undergo PFO closure plus antiplatelet therapy or to receive antiplatelet therapy alone.

Results:

During a median follow-up of 3.2 years, clinical ischemic stroke occurred in 6 of 441 patients (1.4%) in the PFO closure group and in 12 of 223 patients (5.4%) in the antiplatelet-only group (hazard ratio, 0.23; 0.09 to 0.62; P=0.002).

Conclusions:

“Among patients with a PFO who had had a cryptogenic stroke, the risk of subsequent ischemic stroke was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone; however, PFO closure was associated with higher rates of device complications and atrial fibrillation.”

Mas JL, Derumeaux G, Guillon B, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med 2017; 377: 1011–

In a multicenter, randomised, open-label trial patients 16-60 years of age who had had a recent stroke attributed to PFO, to transcatheter PFO closure plus long-term antiplatelet therapy, antiplatelet therapy alone or oral anticoagulation.

Results:

No stroke occurred among patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet- only group (hazard ratio, 0.03; 0 to 0.26; P<0.001). Large number of patients discontinued anti-coagulation in the anti-coagulant group and statistical significance was not analysed because the study was not adequately powered to compare outcomes.

Conclusion:

“Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation.”

Lee PH, Song J-K, Kim JS, et al. Cryptogenic stroke and high-risk patent foramen ovale: the DEFENSE-PFO Trial. J Am Coll Cardiol 2018; 71: 2335–

Patients with cryptogenic stroke and high-risk PFO were divided between a transcatheter PFO closure and a medication-only group.

Results:

No events occurred in the PFO closure group. 12.9% of patients in the medication group had an event (p= 0.023).

Conclusion:

“PFO closure in patients with high-risk PFO characteristics resulted in a lower rate of the primary endpoint as well as stroke recurrence”