I. What every physician needs to know.
Renal artery stenosis is a disease process that leads to narrowing of unilateral or bilateral renal arteries. There are two main pathophysiologic processes that lead to this disease. One of which is atherosclerosis of the renal artery. This process progresses in the same way that cardiac or peripheral artery atherosclerosis occurs.
These lesions begin as smooth muscle and intimal thickening, usually at vessel branch points. They progress with deposition of lipid, T cells and macrophages and can progress to fibroatheromas. This is frequently seen in men that are 45 years of age or older and most frequently effects the ostial region of the renal artery or the proximal section of the vessel. Atherosclerosis of the renal arteries is often found incidentally during cardiac catheterization. These incidental findings are not always clinically significant. Lesions that warrant medical treatment or further intervention are stenotic lesions greater than 70 percent in the setting of clinical findings suggestive of secondary hypertension.
Fibromuscular dysplasia is another cause of renal artery stenosis. This disease is caused by hyperplasia of any of the layers of the vessel wall, but most frequently occurs due to medial fibroplasia. This pathophysiology is seen most often in women younger than 50 years of age and is usually located in the distal main or intra-renal branches of the renal artery.
II. Diagnostic Confirmation: Are you sure your patient has renal artery stenosis?
Renal artery stenosis is confirmed through imaging. Please see the section on diagnostic imaging to further understand the most appropriate modalities to make this diagnosis. However, the finding of renal artery stenosis is often incidental. To determine if intervention is needed the practitioner must assess if the stenosis is clinically significant or just an incidental finding.
Those that are contributing to an acute rise in previously controlled blood pressure, refractory hypertension (uncontrolled on three medications including a diuretic), recurrent bouts of pulmonary edema, patients younger than 30 with no family history of hypertension, patients older than 55 with new onset stage two hypertension, patients found to have asymmetry of their kidneys of greater than 1.5cm, or a severe rise in creatinine with addition of an angiotensin converting enzyme (ace) inhibitor, are likely to have their renal artery stenosis as a contributing factor to their hypertension or chronic kidney disease.
A. History Part I: Pattern Recognition:
The typical patient with clinically significant renal artery stenosis has evidence of secondary hypertension in the setting of renal artery stenosis greater than 70 percent. Please see the above diagnostic confirmation section for a discussion of the patients that have historical clues to clinically relevant renal artery stenosis.
B. History Part 2: Prevalence:
There are not that many general population studies to determine the prevalence of this disease process. Most screening studies have been performed on patients that are getting heart catheterizations for presumed cardiac atherosclerotic disease. From the small amount of studies it is estimated that the prevalence in the general population is approximately 7 percent. However, in patients with atherosclerosis in other areas the prevalence seems to be much higher.
For example, in patients with coronary artery disease the prevalence of renal artery stenosis is approximately 11 to 18 percent and is 22 to 60 percent in patients that have known peripheral artery disease. It should be noted that renal artery stenosis accounts for less than 1 percent of mild to moderate hypertension but this rises to a 10 to 40 percent incidence in patients with severe or refractory hypertension. Fibromuscular dysplasia accounts for 10 to 15 percent of the renal artery stenosis that leads to hypertension in adults.
C. History Part 3: Competing diagnoses that can mimic renal artery stenosis.
In patients with refractory or acutely rising hypertension, other causes of secondary hypertension should be considered. This differential contains pheochromocytoma, obstructive sleep apnea, primary hyperaldosteronism, Cushing’s syndrome, coarcation of the aorta, hypothyroidism, primary renal disease, and primary hyperparathyroidism.
D. Physical Examination Findings.
At times a renal bruit can be heard but this finding is not always present.
E. What diagnostic tests should be performed?
Imaging modalities should be obtained to determine this diagnosis. Please see that imaging section for further detail.
1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
There is no laboratory study that will establish this diagnosis. However, patients with this disease should get a basic metabolic profile to determine their creatinine and a lipid profile since this is so closely tied with global atherosclerotic disease including coronary artery disease.
2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
There are many diagnostic studies that can be used that have the appropriate sensitivity and specificity that make them appropriate tools in diagnosing renal artery stenosis. The goal is to find a stenotic lesion of 70 percent or more or a 50 percent lesion with post stenotic dilatation in the setting of clinical clues listed above that will make this finding significant.
Patients with atherosclerotic renal artery stenosis usually have ostial main renal artery disease, and those with fibromuscular dysplasia causing their renal stenosis have more distal stenosis of the main renal artery or stenosis of the intra-renal branches. As a result, digital subtraction angiography is preferred over magnetic resonance angiography (MRA) for patients with fibromuscular dysplasia. The following discussion will focus on imaging modalities that are best for atherosclerotic induced renal artery stenosis.
The gold standard imaging modality for any form of renal artery stenosis is renal arteriography. This is an invasive procedure and over the years noninvasive imaging modalities have improved; this disease is now best diagnosed by non-invasive means. Digital subtraction angiography is the standard in diagnostic imaging for fibromuscular dysplasia. Medial fibroplasia has a typical string and bead appearance. When attempting to diagnose the proximally located athersclerotic renal artery stenosis lesions, the below imaging modalities have a sensitivity and specificity in the upper nineties.
MRA is a first line noninvasive screening tool. It is less effective at finding mid-artery or distal-artery disease so this needs to be considered if the underlying pathophysiology is thought to be fibromuscular dysplasia. Computed tomography (CT) angiography is another highly sensitive and specific imaging modality and can be used to diagnose atherosclerotic renal artery stenosis. It is very specific but less sensitive in diagnosing fibromuscular dysplasia.
Duplex doppler ultrasonography is an excellent diagnostic tool when used by a skilled technician. This tool can not only make the diagnosis, but by calculating a resistive index it can be useful in predicting whether a patient will have a positive response to interventions other than medical management. It bears repeating however that the ultrasonography is highly operator dependent and is not useful if the technician is not skilled in this particular test.
F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.
There are several imaging methods that are not useful when trying to make a diagnosis. These include: IV pyelogram, plasma renin activity, captopril renogram and renal vein renin measurements. These tests should not be used when attempting to make the diagnosis of renal artery stenosis.
III. Default Management.
Default management in any form of renal artery stenosis, be it from atherosclerosis or fibromuscular dysplasia, is medical management. Primarily, this is achieved through blood pressure control. First-line medical management is the use of ACE inhibitors or angiotensin receptor blocking (ARB) agents. Because hypertension is fueled in these patients by a hyperactive renin angiotensin axis and by salt and water retention, these patients may also benefit from a diuretic, specifically thiazide diuretics.
In patients that do not tolerate ACE inhibitor or ARB therapy, or are very volume sensitive and do not tolerate diuretic therapy, calcium channel blockers and beta-blockers should be used for blood pressure control. In specific patients, intervention may be performed if medical management has not been effective. In carefully selected patients, performing percutaneous transluminal angiography (PTA) with stent placement can help control blood pressure and stabilize or even improve renal function.
Patients that should be considered for PTA with stent placement are those that have a hemodynamically significant lesion (as described in the diagnostic imaging section), refractory or malignant hypertension that is unable to be controlled with medication, and patients that have recurrent episodes of acute pulmonary edema. In these patients, angioplasty with stent placement provides the smallest risk of restenosis. Blood pressure normalization occurs in 8 to 20 percent of patients, improvement occurs in 50 to 60 percent of patients, and no change is seen in 20 to 30 percent of patients after stent placement.
The best results are seen in patients that have disease in only one kidney and have experienced an acute rise in previously controlled blood pressure. In patients with bilateral disease that undergo stent placement, 50 percent have no change in renal function, 20 to 25 percent have improvement in their renal function and 15 to 25 percent have worsening of their renal function. It is important to note that revascularization has never been proven to have a mortality benefit.
There have been many small studies that have compared medical management with revascularization. They are all fraught with problems, however, the best powered and most frequently cited study is the ASTRAL study. This study found no significant benefit in blood pressure control, renal insufficiency, or mortality when medical management was compared with percutaneous intervention.
It should be mentioned that surgery can be used instead of PTA for patients that have failed medical management and have complicated or multiple renal artery involvement. At an experienced center, the mortality rate is approximately 3% with this procedure. Patients with fibromuscular dysplasia are often managed with angioplasty without stenting.
A. Immediate management.
There is no immediate management for renal artery stenosis per se. However, patients that present with malignant hypertension or acute pulmonary edema should be managed appropriately for that acute condition.
B. Physical Examination Tips to Guide Management.
There are not overt physical exam findings that need to be monitored while a patient is in the hospital. However, if the patient presents with acute onset pulmonary edema from their renal artery stenosis induced hypertension, daily lung exams would be useful to monitor resolution of pulmonary edema. Furthermore, if a patient has recently had an intervention for this problem, specifically angioplasty with or without stent placement, their groin should be checked for evidence of hematoma or bruit, and their femoral and distal pulses should be checked to make sure there is no evidence of dissection or distal atherosclerotic emboli.
C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.
Renal function tests should be monitored closely during medical management.
D. Long-term management.
Please see default management for discussion of long-term management. One point that should be stressed is that patients with atherosclerotic renal artery stenosis are at higher risk for cardiovascular and cerebrovascular events. As a result they should be treated as if they have a cardiovascular risk equivalent. Over the long-term this means controlling their blood pressure, maintaining a low density lipoprotein value of less than 100, providing appropriate glycemic control in patients with diabetes, using prophylactic aspirin unless contraindicated, and counseling on smoking cessation when appropriate.
E. Common Pitfalls and Side-Effects of Management
As mentioned in other sections, ACE inhibitor and ARB use are the cornerstone of anti-hypertensive therapy. However, because they lead to efferent artery dilatation in patients with stenosis of their main renal artery, this can cause a problem in autoregulation leading to a decreased glomerular filtration rate. Patients that experience a 30 percent increase in their creatinine should be taken off their ACE inhibitor, ARB or direct renin inhibitor. Be aware that volume status plays an important role in this process as well, and patients that are volume depleted should be repleted prior to making this decision.
Because of the physiology discussed above, there has been concern that ACE inhibitor or ARB therapy may over time worsen renal ischemia. However, there is no good data to support this theory. Therefore, these medications are still recommended as first-line agents to treat blood pressure with the caveat that they should be closely monitored.
IV. Management with Co-Morbidities
A. Renal Insufficiency.
In patients with renal insufficiency the use of ACE inhibitors, ARBs and direct renin inhibitors need to be monitored very closely. In patients that have an increase in creatinine of greater than 30 percent when on these medications, alternate anti-hypertensives like calcium channel and beta-blockers should be considered. When there is significant concern about renal ischemia leading to progression of renal insufficiency, especially when bilateral renal artery stenosis is present, more definitive treatments like percutaneous transluminal angiography with stenting or vascular surgery may be considered to help slow or prevent progression of renal disease.
B. Liver Insufficiency.
No change in standard management.
C. Systolic and Diastolic Heart Failure
Heart failure, especially when frequent exacerbations occur on optimal medical management, may be an indication for patients to get percutaneous transluminal angioplasty with stent placement or surgery to bypass their renal artery stenosis.
D. Coronary Artery Disease or Peripheral Vascular Disease
Frequent episodes of unstable angina may be exacerbated by uncontrolled blood pressure that is made worse by renal artery stenosis. In these instances, intervention with angioplasty and stent placement or surgical bypass may help with control of the anginal symptoms.
E. Diabetes or other Endocrine issues
No change in standard management.
No change in standard management.
G. Immunosuppression (HIV, chronic steroids, etc).
No change in standard management.
H. Primary Lung Disease (COPD, Asthma, ILD)
No change in standard management.
I. Gastrointestinal or Nutrition Issues
No change in standard management.
J. Hematologic or Coagulation Issues
No change in standard management.
K. Dementia or Psychiatric Illness/Treatment
No change in standard management.
V. Transitions of Care
A. Sign-out considerations While Hospitalized.
Consider alerting the covering physician to your patient’s renal function when signing out, and if renal insufficiency is present note if it would require them to renally dose medications overnight.
B. Anticipated Length of Stay.
The majority of the diagnosis and treatment for renal artery stenosis can be performed as an outpatient. The only instances that would likely warrant an inpatient hospitalization are hypertensive emergencies or episodes of acute pulmonary edema precipitated by renal artery stenosis. In these instances, short hospitalizations to control blood pressure adequately is all that is required.
C. When is the Patient Ready for Discharge.
Patients are ready for discharge when their blood pressure is reasonably controlled, with a stable creatinine and no evidence of active end organ damage from their hypertension.
D. Arranging for Clinic Follow-up
1. When should clinic follow up be arranged and with whom.
Patients should follow-up within a month with an internist to ensure that their blood pressure is well controlled and that their cardiac risk factors are being controlled appropriately. If the patient has renal insufficiency, appropriate follow-up with nephrology should be made to monitor this problem and plan for dialysis if necessary.
2. What tests should be conducted prior to discharge to enable best clinic first visit.
Baseline laboratory values are important, especially a creatinine since medications that effect renal function will likely be prescribed. Patients with renal artery stenosis due to atherosclerosis are at an increased risk for cardiovascular disease, so a baseline lipid profile should be obtained to determine if medical intervention is necessary.
3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.
If an ACE inhibitor has already been prescribed, a creatinine and potassium level should be drawn prior to their clinic visit. Also a repeat lipid value may be necessary if a statin was initiated during their hospitalization.
E. Placement Considerations.
Patients will likely be discharged home without any home health needs.
F. Prognosis and Patient Counseling.
While atherosclerotic renal artery stenosis usually progresses it is not clear if this is always clinically significant. However, patients are at increased (2 to 4-fold) risk for cardiovascular events. Furthermore, patients that progress to dialysis from chronic kidney disease have a high mortality rate. This may be related to their overall atherosclerotic burden.
VI. Patient Safety and Quality Measures
A. Core Indicator Standards and Documentation.
There are no specific core indicators for renal artery stenosis. However, it is a cardiac disease equivalent and practitioners should adhere to the standards for lipid control, blood pressure control and glycemic control in these patients.
What's the evidence?
Saflan, RD, Textor, SC. “Renal Artery Stenosis”. N Engl J Med. vol. 344. 2001. pp. 431-442.
Hirsch, AT, Haskal, ZJ, Hertzer, NR, Bakal, CW, Creager, MA, Halperin, JL, Hiratzka, LF, Murphy, WR, Olin, JW, Puschett, JB, Rosenfiield, KA, Sacks, D, Stanley, JC, Taylor LM, Jr, White, CJ, White, J, White, RA, Antman, EM, Smith SC, Jr, Adams, CD, Anderson, JL, Faxon, DP, Fuster, V, Gibbons, RJ, Hunt, SA, Jacobs, AK, Nishimura, R, Ornato, JP, Page, RL, Riegel, B. “ACC/AHA Guidelines for the Management of Patients with Peripheral Arterial Disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Associations for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society for interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines(writing committee to develop guidelines for the management of patients with peripheral arterial disease)-summary of recommendations”. J Vasc Interv Radiol. vol. 17. 2006. pp. 1383-1397.
Dworkin, LD, Cooper, CJ. “Clinical practice. Renal-artery stenosis”. N Engl J Med. vol. 361. 2009. pp. 1972-1978.
Postma, CT, Joosten, FB, Rosenbusch, G, Thien, T. “Magnetic resonance angiography has a high reliability in the detection of renal artery stenosis”. Am J Hypertens. vol. 10. 1997. pp. 957-963.
Rieumont, MJ, Kaufman, JA, Geller, SC, Yucel, EK, Cambria, RP, Fang, LS, Bazari, H, Waltman, AC. “Evaluation of renal artery stenosis with dynamic gadolinium-enhanced MR angiography”. AJR Am J Roentgenol. vol. 169. 1997. pp. 39-44.
Wheatley, K, Ives, N, Gray, R, Kalra, PA, Moss, JG, Baigent, C, Carr, S, Chalmers, N, Eadinton, D, Hamilton, G, Lipkin, G, Nicholson, A, Coble, J. “Revascularization versus medical therapy for renal-artery stenosis”. N Engl J Med. vol. 361. 2009. pp. 1953-1962.
Bax, L, Woittiez, AJ, Kouwenberg, HJ, Mali, WP, Buskens, E, Beek, FJ, Braam, B, Huysmans, FT, Schultze Kool, LJ, Rutten, MJ, Doorenbos, CJ, Aarts, JC, Rabelink, TJ, Plouin, PF, Raynaud, A, van Montfrans, GA, Reekers, JA, van den Meiracker, AH, Pattynama, PM, van de Ven, PJ, Vroegindeweij, D, Kroon, AA, de Haan, MW, Postma, CT, Beutler, JJ. “Stent placement in patients with atherosclerotic renal artery stenoisis and impaired renal function: a randomized trial”. Ann Intern Med. vol. 150. 2009. pp. 840-848.
Kumbhani, DJ, Bavry, AA, Harvey, JE, de Souza, R, Scarpioni, R, Bhatt, DL, Kapadia, SR. “Clinical outcomes after percutaneous revascularization versus medical managment in patients with significant renal artery stenosis: a meta-analysis of randomized controlled trials”. Am Heart J. vol. 161. 2011. pp. 622-630.
Lawrie, GM, Morris GC, Jr, Glaeser, DH, DeBakey, ME. “Renovascular recontruction: factors affecting long-term prognosis in 919 patients followed up to 31 years”. Am J Cardiol. vol. 63. 1989. pp. 1085-1092.
Plouin, PF, Chatellier, G, Darne, B, Raynaud, A. “Blood pressure outcome of angioplasty in atherosclerotic renal artery stenosis: a randomized trial. Essai Multicentrique Medicaments vs Angioplastie (EMMA) Study Group”. Hypertension. vol. 31. 1998. pp. 823-829.
van Jaarsveld, BC, Krijnen, P, Pieterman, H, Derkx, FH, Deinum, J, Postma, CT, Dees, A, Woittiez, AJ, Bartelink, AK, Man in ‘t Veld, AJ, Schalekamp, MA. “The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery stenosis. Dutch Renal Artery Stenosis Intervention Cooperative Study Group”. N Engl J Med. vol. 342. 2000. pp. 1007-1014.
Krijnen, P, van Jaarsveld, BC, Steyerberg, EW, Man in ‘t Veld, AJ, Schalekamp, MA, Habbema, JD. “A clinical prediction rule for renal artery stenosis”. Ann Intern Med. vol. 129. 1998. pp. 705-711.
Pascual, A, Bush, HS, Copley, JB. “Renal fibromuscular dysplasia in elderly persons”. Am J Kidney Dis. vol. 45. 2005. pp. e63-66.
Stanley, JC, Gewertz, BL, Bove, EL, Sottiurai, V, Fry, WJ. “Arterial fibrodysplasia. Histopathologic character and current etiologic concepts”. Arch Surg. vol. 110. 1975. pp. 561-566.
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- I. What every physician needs to know.
- A. History Part I: Pattern Recognition:
- B. History Part 2: Prevalence:
- C. History Part 3: Competing diagnoses that can mimic renal artery stenosis.
- D. Physical Examination Findings.
- E. What diagnostic tests should be performed?
- 1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
- 2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
- F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.
- III. Default Management.
- A. Immediate management.
- B. Physical Examination Tips to Guide Management.
- C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.
- D. Long-term management.
- E. Common Pitfalls and Side-Effects of Management
- IV. Management with Co-Morbidities
- A. Renal Insufficiency.
- B. Liver Insufficiency.
- C. Systolic and Diastolic Heart Failure
- D. Coronary Artery Disease or Peripheral Vascular Disease
- E. Diabetes or other Endocrine issues
- F. Malignancy
- G. Immunosuppression (HIV, chronic steroids, etc).
- H. Primary Lung Disease (COPD, Asthma, ILD)
- I. Gastrointestinal or Nutrition Issues
- J. Hematologic or Coagulation Issues
- K. Dementia or Psychiatric Illness/Treatment
- V. Transitions of Care
- A. Sign-out considerations While Hospitalized.
- B. Anticipated Length of Stay.
- C. When is the Patient Ready for Discharge.
- D. Arranging for Clinic Follow-up
- 1. When should clinic follow up be arranged and with whom.
- 2. What tests should be conducted prior to discharge to enable best clinic first visit.
- 3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.
- E. Placement Considerations.
- F. Prognosis and Patient Counseling.
- VI. Patient Safety and Quality Measures
- A. Core Indicator Standards and Documentation.
- What's the evidence?