Renal artery stenosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shivam Singla, M.D.[2]

• Renal artery stenosis (RAS) is defined as the unilateral or bilateral progressive narrowing of the renal arteries or their proximal branches of more than 50% in diameter.
• RAS is a heterogeneous group of diseases that most commonly include: fibromuscular dysplasia (FMD) and atherosclerotic renal artery stenosis (ARAS).
• Although renal artery stenosis may be an isolated asymptomatic condition,
• It may commonly lead to secondary hypertension that is thus called renovascular hypertension (RVHT), ischemic nephropathy, and chronic renal insufficiency.

• Approximately 90% of renal artery stenosis cases occur due to progressive atherosclerosis.
• The ostium and proximal third of the renal arteries are the most commonly involved regions in atherosclerosis.
• Segmental and diffuse atherosclerosis may still be seen in the minority of patients, especially in context of chronic kidney disease and poor renal survival.

• The main pathophysiological mechanism behind renal artery stenosis is reduction in renal blood flow
• Secondary to renal artery stenosis which stimulates renin release from the juxtaglomerular apparatus through activation of the tubuloglomerular feedback, baroreceptor reflex, and the sympathetic nervous system.

• Elevated angiotensin II activities in turn cause elevation of the arterial pressure and other effects including aldosterone secretion, sodium retention, and left ventricular hypertrophy and remodeling.

• Renal artery stenosis is most commonly caused by the development of atherosclerotic plaque in the renal arteries (termed atherosclerotic renal artery stenosis).
• Less frequently, it is caused by fibromuscular dysplasia.

• Renal artery stenosis may be classified according to whether there is unilateral or bilateral involvement of the renal arteries.

• Additionally, renal artery stenosis is classified anatomically according to the severity of luminal narrowing.

• The following criteria are used according to most published studies about ARAS.

• To note, some studies have different classification criteria than those listed above, with “mild disease” starting after 50% of luminal narrowing. Such classification remains coherent with the definition of ARAS as narrowing > 50%.
• Another classification is based on hemodynamic function in RAS. This classification simply differentiates between hemodynamically insignificant Renal artery stenosis (< 75% stenosis) and hemodynamically significant Renal artery stenosis (> 75% stenosis).

• Atherosclerotic renal artery stenosis (ARAS) is considered a disease of the elderly.

• The true prevalence of ARAS has not been reliably determined and prevalence rates present so far may in fact be an underestimate or an overestimate of the true prevalence due to the varying selection criteria in different studies.

• The prevalence of ARAS increases substantially among patients with cardiovascular co-morbidities, such as diabetes mellitus, dyslipidemia, essential hypertension, and known coronary or peripheral artery disease.

• Risk factors for ARAS, per se, are poorly studied. The most commonly associated risk factors are:
  • Atherosclerosis
  • Advanced age
  • Dyslipidemia
  • Diabetes mellitus
  • Smoking
  • Hypertension

• Non-invasive diagnosis is the first line for the screening of ARAS.

• Doppler ultrasonography, CTA, and MRA may all be used to diagnose ARAS.

• The invasive diagnostic technique, such as renal angiography, is considered the gold standard for diagnosis and may be used when
• Concomitant catheterizations are needed or when previously performed non-invasive techniques yielded equivocal results.

• Medical therapy is considered the first line of management for patients with ARAS.

• Several anti-hypertensive medications have proven to be efficacious in ARAS patients.

• According to the 2013 ACC/AHA Guidelines for the Management of PAD, ACE-I and CCB may be used in patients with RAS because they have an effect on both lowering BP and delaying the renal disease.

• Other blood pressure-lowering medications include beta-blockers, hydrazine, and chlorothiazide.

• Although ARBs may be used as well, they still have level B evidence for use in ARAS because trials have not been conducted on the use of ARBs in such patients.

• Angioplasty and stent implantation were previously recommended by the 2013 ACC/AHA Guidelines. However, emerging data from the CORAL trial showed that although there are high technical success rates with angioplasty/stenting, the clinical endpoints are inconsistently and modestly modified. Therefore, raising the suspicion that PRI (percutaneous renal interventions) can incur substantial costs without a significant public health advantage

• Vascular reconstruction of the renal arteries may be indicated in a small minority of patients. However, surgical reconstruction is associated with complications and carries a 5-15% for surgical re-intervention.

• Renovascular hypertension
• Acute renal failure
• Atherosclerosis
• Chronic glomerulonephritis
• Hypersensitivity nephropathy
• Hypertension
• Malignant hypertension
• Nephrosclerosis
• Renovascular hypertension
• Uremia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shivam Singla, M.D.[2]

The reduction in renal blood flow secondary to renal artery stenosis stimulates renin release from the juxtaglomerular apparatus through activation of the tubuloglomerular feedback, baroreceptor reflex, and the sympathetic nervous system. Elevated angiotensin II activities in turn cause elevation of the arterial pressure and other effects including aldosterone secretion, sodium retention, and left ventricular hypertrophy and remodeling.

• Renal artery stenosis means the narrowing of both renal arteries leading to the obstruction of blood flow and resulting in the stimulation of RAAS.
• The blood flow to the kidneys is generally greater than perfusion to any other organ and the GFR mainly depends on the glomerular capillary hydrostatic pressure.
• In patients with RAS, the reduced blood flow to the kidneys leads to the formation of collateral blood vessels and increases secretion of renin by juxtaglomerular apparatus^[1]and activation of the renin-angiotensin-aldosterone system^[2]
• Renin converts angiotensinogen to angiotensin I and then further gets converted to Angiotensin II with the help of ACE
• This angiotensin II directly causes vasoconstriction and also increases aldosterone which results in the retention of sodium and water thus leads to the development of renovascular hypertension that is also called secondary hypertension.
• Prolonged hypo-perfusion to the kidneys resulting in chronic stimulation and hyperplasia of the juxtaglomerular apparatus. This prolonged ischemia further leads to renal insufficiency and in turn progressive renal atrophy^[3].

Glomerular filtration rate (GFR) is auto-regulated with the help of angiotensin II and numerous other modulators. The GFR gets affected when the renal perfusion drops below 70 mmHg^[4]. the apparent change in GFR is observed once the arterial lumen narrows by more than 50%. Numerous studies reported that GFR is reduced when altogether there is a reduction in renal perfusion pressure by more than 40% and a reduction in mean renal blood flow by 30%. However, even after this, the kidneys cortex and medulla can adapt without the development of severe hypoxia. So early disease can be managed with the medical approach and that can prevent the development of progressive function loss and fibrosis. But in cases with more significant stenosis around 70-80%, there is the development of apparent cortical hypoxia and this hypoxia further leads to the rarefaction of microvessels and ultimately leads to the development of interstitial fibrosis^[3]. Therefore the loss of renal function and progressive renal disease. Eventually, it becomes irreversible and restoration of blood flow to the kidneys will not help in getting back the kidney functions.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shivam Singla, M.D.[2]

Renal artery stenosis is most commonly caused by the development of atherosclerotic plaque in the renal arteries (termed atherosclerotic renal artery stenosis). Less frequently, it is caused by fibromuscular dysplasia.

Unilateral Renal artery stenosis has two major causes:

1) Atherosclerosis^[1]: Most common cause seen in almost 60-90 percent of the cases associated with renal artery stenosis. Atherosclerosis mostly affects men over the age of 45 years and mainly involves the proximal part of the main renal artery. Although this condition is also commonly seen as an isolated lesion even in patients not having the underlying atherosclerotic disease. The risk factors associated with atherosclerosis are dyslipidemia, cigarette smoking, virus infection, immune damage, and elevated concentrations of homocysteine.

2) Fibromuscular dysplasia^[2][3]: This is responsible for causing renal artery stenosis in the remaining 10-30 percent of cases. This is most commonly seen in women under the age of 50 years and mainly involves middle and distal renal arteries and typically involves the middle and distal main renal artery or the intrarenal branches.

3) In, Less than 10 percent of the patient population other less common factors play a role like

– Thromboembolic disease

– Aortic aneurysms

– Takayasu arteritis

– Polyarteritis nodosa

– Retroperitoneal fibrosis.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Shivam Singla, M.D.[2]

Renal artery stenosis classification is doner with the help of a doppler scanning of the renal artery.

According to the American heart associated AHA classification, the renal artery stenosis is divided into grade I, II, III depending upon the Hypertension/Normotension and Renal function. According to AHA^[1]

Grade 1- Renal artery stenosis is present but the patient is Normotensive with a normal renal function.

Grade 2- Renal artery stenosis is present but the patient is having hypertension that is medically controlled with a normal renal function.

Grade 3- Renal artery stenosis is present but the patient is having hypertension or volume overloaded with abnormal renal function.

Renal artery stenosis may be classified according to whether there is unilateral or bilateral involvement of the renal arteries. Additionally, renal artery stenosis is often classified anatomically according to severity of luminal narrowing. The following criteria are used according to most published studies about atherosclerosis renal artery stenosis.^[2][3]

To note, some studies have different classification criteria than those listed above, with “mild disease” starting after 50% of luminal narrowing. Such classification remains coherent with the definition of atherosclerotic renal artery stenosis as narrowing > 50%.^[4]

Another classification is based on hemodynamic function in renal artery stenosis. This classification simply differentiates between hemodynamically insignificant renal artery stenosis (< 75% stenosis) and hemodynamically significant renal artery stenosis (> 75% stenosis).^[5]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shivam Singla, M.D.[2] Yazan Daaboul, Serge Korjian

Atherosclerotic renal artery stenosis (ARAS) is considered a disease of the elderly. The true prevalence of ARAS has not been reliably determined and prevalence rates present so far may in fact be an underestimate or an overestimate of the true prevalence due to selection criteria in different studies. The prevalence of ARAS increases substantially among patients with cardiovascular co-morbidities, such as diabetes mellitus, dyslipidemia, essential hypertension, and known coronary or peripheral artery disease.

Renal artery stenosis considered a disease of the elderly.^[1] It most commonly affects patients with cardiovascular co-morbidities, such as those with diabetes mellitus, coronary and peripheral artery disease, dyslipidemia, essential hypertension, and smoking history.^[2][3][4][5]

• It is difficult to assess the real incidence and prevalence of renal artery stenosis because most patients with the disease are in fact asymptomatic.
• In one study that involved 14,152 patients undergoing abdominal aortography, approximately 10% of the patients had RAS and 1.3% had bilateral RAS, 60% of which were considered significant stenosis.^[5]
• Autopsy findings among 5194 patients between 1980 and 1988 showed that 4.3% of all patients RAS, most of which were not diagnosed.^[2] The frequency of RAS among patients with diabetes and hypertension was higher, reaching up to 10% of all patients. ^[2]
• Atherosclerotic renal artery stenosis affects approximately 0.5-7% of the U.S. population above the age of 65 years. It is present in almost 5% of patients with chronic kidney disease.^[6][7]
• Although stenosis may progress in 30-53% of patients within only 2-5 years. after diagnosis, only 3-15% of patient with ARAS progress to total occlusion of the renal arteries.^{[4][3][4][8][9]} The definition of disease progression, however, may vary between individual studies.
• To date, there is no reliable information about the prevalence of secondary hypertension due to renal artery stenosis. Follow-up and prognosis for hypertensive patients with renal artery stenosis has not yet been achieved.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shivam Singla, M.D.[2] Yazan Daaboul, Serge Korjian

Cardiovascular risk factors are considered the most important risk factors for the development of Renal artery stenosis. The Most important risk factors are advanced age, smoking, hypertension, dyslipidemia, diabetes, and known vascular disease.

In both men and females, RAS may develop. It is more common in elderly persons. Cardiovascular risk factors are the most important risk factors for the initiation and progression of atherosclerotic renal artery disease (ARAS). The most common risk factors associated with renal artery stenosis are^[1][2][3]:

– Diet having a high content of cholesterol, carbohydrates, and sodium

– Hypertension

– Diabetes

– Peripheral vascular disease

– Coronary artery disease

– Family history of cardiovascular disease

– Diet rich in cholesterol

– Sedentary lifestyle

– Obesity

– Smoking

It is now clear that the prevalence of ARAS is higher among patients with hypertension, and among those who had prior cardiac catheterization procedures or with known coronary artery disease. The prevalence of ARAS in these patients increases drastically to reach up to 30-50% of all patients.^[2][4][5][6]