RENAL ARTERY
STENOSIS

RENAL ARTERY STENOSIS

INTRODUCTION

· Commonest curable form of hypertension.

· Responsible for 0.5-1.0% of cases of hypertension.

· Bilateral lesions are present in 25-30% of patients with renal artery stenosis (RAS).

· RAS can occur alone (isolated anatomical RAS) without hypertension. RAS is found in normotensive and hypertensive individuals, especially when there is co-existing atherosclerosis.

· RAS may complicate the course of patients with essential hypertension (EH).

· Majority of patients with RAS who have hypertension have EH as suggested by persistence of hypertension after successful revascularization (treatment of RAS).

· In evaluation of hypertensive patients with RAS, it is important to find if the renal artery lesion is causing hypertension.

Spectrum of RAS

· Isolated RAS.

· RAS causing hypertension i.e., renovascular hypertension.

· RAS in association with EH.

· RAS causing renal insufficiency (ischemic nephropathy).

· RAS causing both renovascular hypertension and renal insufficiency.

Renal Artery Stenosis

Pathological Types

1. Atherosclerotic RAS

· Accounts for 90% of cases of RAS.

· Usually involves the ostium and proximal third of the main RA.

· Prevalence increases with age, presence of cardiovascular risk factors, e.g., hypertension, diabetes, cigarette smoking, and in patients with other atherosclerotic diseases, e.g., coronary and cerebrovascular diseases.

· It is progressive in more than 50% of patients and in 3 to 16% the renal artery becomes totally occluded.

· There is mild to severe reduction in renal function at initial diagnosis.

2. Fibromuscular Dysplasia

· Accounts for 10% of cases of RAS.

· In 90% of cases fibromuscular dysplasia involves the media.

· Involves the distal two thirds of RA and its branches.

· Lesions appear as multifocal sequential areas of fibrosis within the media of the arterial wall, disrupting the internal elastic membrane of the media producing beaded aneurysmal appearance with a characteristic renal angiographic picture - string of beads.

· The disease progresses very slowly, rate of progression is slower than that of atherosclerotic lesions.

· Renal function tests (BUN and serum creatinine) are usually normal.

· It is a disease of girls and young women between 15 and 50 years of age.

Mechanism of Hypertension in RAS

· Reduced renal perfusion will activate the renin-angiotensin system.

· Increased formation of angiotension-II (A II) will increase blood pressure through:

a. Direct vasoconstriction.

b. Renal Artery Stenosis

Increased aldosterone production with subsequent salt and water retention.

c. Stimulation of sympathetic nervous system.

Diagnosis of Renovascular Hypertension and RAS

- Clinical Suspicion

1. Sudden onset of severe hypertension in a previously normotensive individual.

2. Sudden loss of control of hypertension (rise in BP) in a patient treated for EH in the absence of an obvious cause.

3. Recent history of hypertension in a patient younger than 30 years and older than 50 years.

4. Hypertension, which is difficult to control in spite of triple drug therapy.

5. Any patient with accelerated or malignant hypertension (retinopathy grades III or IV - hemorrhages, exudates, papilledema).

6. Sudden and severe deterioration of kidney function (rise in serum creatinine) after initiation of angiotensin - converting enzyme inhibitor, e.g., captopril therapy for the treatment of hypertension.

7. Presence of abdominal bruits (systolic and early diastolic) in the area between the umbilicus and costal margin or in the flanks.

8. Hypertension associated with unilateral small kidney.

9. Unexplained or progressive azotemia (ischemic nephropathy).

The absence of hypertension does not exclude the possibility of RAS.

Diagnostic Procedures

A- Biochemical Tests

1. Serum Creatinine: - assess overall renal function

- elevated in ischemic nephropathy and after treatment with ACE-inhibitors.

Renal Artery Stenosis

2. Plasma renin activity (PRA): of limited diagnostic valve.

3. Captopril Test: Estimation of BP and PRA before and 60 minutes after administration of oral captopril 50 mg (for details, see chapter 5 - Captopril Test). An increase in PRA of more than 150% of initial value suggests RVH. When the post-captopril PRA is more than 5.7 ng/ml/h the test is 100% sensitive and 86% specific for patients not receiving diuretics.

4. Measurements of PRA in samples from renal veins - to reveal the functional significance of unilateral RAS.

- Increased renin secretion from the side of stenosis.

- A ratio of PRA in the vein from the affected kidney of 1.6 or greater than the unaffected kidney predicts the humoral and hemodynamic significance of unilateral RAS.

- Requires introduction of venous catheter into the femoral vein and catheterizing the renal veins to obtain blood samples for PRA.

- There are false positive and false negative results.

The above PRA studies are of limited value in elderly patients with atherosclerotic RAS, since hypertension in these patients is not renin dependant. They are more useful in patients with fibromuscular dysplasia.

B- Imaging Techniques

1. Rapid Sequence Intravenous Pyelography (IVP):

- Of limited value: high false positive and false negative results.

- Very rarely done.

- There is a smaller kidney and delayed appearance and disappearance of the dye on the affected side. The left kidney is normally 0.5 cm longer than the right, 1.0 to 1.5 cm difference between the two kidneys is abnormal.

2. Abdominal Ultrasound:

- Renal Artery Stenosis

Assess kidney size and state of renal parenchyma.

3. Duplex Ultrasonography of Renal Arteries:

- Diagnostic technique of choice in elderly patients suspected of having RAS.

- Provides the following information:

a) images of the renal arteries

b) blood flow velocity

c) pressure wave form.

- Criteria of a Narrowing of the Renal Artery

1. Stenosis of 50% or more of the luminal diameter.

2. Increased flow in comparison to the abdominal aorta. The level of this difference is directly proportional to the extent of the stenosis.

3. Comparing the systolic and end-diastolic flow in the involved renal artery to that in the aorta.

Resistance index = 1-end-diastolic velocity/maximal systolic velocity X 100. A high resistance index of 80 or greater identifies patients with RAS in whom angioplasty or surgery will not improve renal function, BP or kidney survival.

4. The specific Doppler wave forms distal to the vascular lesion are enhanced by captopril and the sensitivity may increase to 100% following captopril administration.

- The technique is noninvasive, does not require discontinuing antihypertensive medications. However, it is time consuming, operator dependant, technically difficult and requires extensive training.

- There is 10 to 20% rate of failure due to operator's inexperience, the presence of obesity or bowel gas. 

4. Magnetic Resonance Angiography (MRA):

- Renal Artery Stenosis

MRA with gadolinium-based contrast agents, can sharply delineate the entire length of the major renal arteries, but is suboptimal for distal, intrarenal and accessory renal arteries.

- It is recommended in patients with renal insufficiency and in patients who do not require invasive angiography.

5. Radioisotopic Renography - Renal Scan:

- Most widely used for detection of RAS.

- Have largely replaced rapid sequence IVP.

- Radionuclide most frequently employed are technetium-99 and 131I-hippuran.

- Findings which indicate RAS:

1. Decreased relative uptake by the involved kidney

2. Twice the usual time (5 min) to peak uptake of the isotope on the affected side.

3. Delayed washout of the isotope of more than 5 minutes on the involved side compared with the contra lateral kidney.

6. Renal Scan Combined with ACE-Inhibitor:

- Improves diagnostic value of renal scan by pre-application of ACE-inhibitor. Acute ACE inhibition causes reduction in glomerular filtration in the post-stenotic kidney with decrease in renal function.

- Reduced absorption of the isotope in the post-stenotic kidney - resulting in a smaller and delayed peak activity and slower washout.

- A normal renal scan following ACE-inhibition excludes with high probability hemodynamically significant RAS.

7. Intravenous Digital Subtraction Angiography (DSA):

- DSA is of limited value because of poor visualization of renal

Renal Artery Stenosis arteries.

- Only used in cases of suspected RAS with severe atherosclerotic changes in femoral arteries or abdominal aorta.

8. Renal Arteriography:

- Selective visulaization of renal arteries is the only certain procedure for detecting renovascular disease.

- It differentiates between atherosclerotic and fibromuscular dysplasia.- It assesses the distal and peripheral side branches.

- Only justified in selected cases.

TREATMENT

- The primary goal is to preserve renal function and to control BP.

- There are three therapeutic approaches.

1. Medical treatment

2. Surgical revascularization

3. Percutaneous interventions

- Treatment must be individualized and the type of treatment will depend upon:

1. Age.

2. Type and severity of lesion and whether unilateral or bilateral.

3. Severity of hypertension and its response to medical therapy.

4. State of kidney function-serum creatinine concentration.

5. Likehood that correction of RAS will improve BP control and renal function.

6. Presence of co-existing disease.

7. Risk of invasive procedures.

Renal Artery Stenosis

1. Medical Treatment

Medical Treatment for Atherosclerotic RAS

· Aggressive lipid lowering and control of other cardiovascular risk factors, e.g., cigarette smoking, diabetes mellitus.

· Aspirin

· Adequate control of BP

- Unilateral RAS with Preserved Renal Function:

ACE-inhibitors or angiotensin receptor blockers are effective in 86 to 92% of patients with atherosclerotic RAS.

Renal insufficiency can develop acutely or chronically with ACE-inhibitors when there is bilateral RAS or sole functioning kidney. Renal insufficiency is potentiated by sodium depletion and pre-existing renal disease and it is reversible if detected early.

- Bilateral RAS:

Calcium channel blockers

· Follow-up of kidney function and regular renal scans are needed. Impaired functional flow to the stenotic kidney on renal scan is justification for renal revascularization.

Medical Treatment for Fibromuscular Dysplasia

ACE-inhibitors are the drugs of choice, when there is no contraindication.

2. Surgical Revascularization

- Coeliac or mesentric branch renal artery bypass have replaced aorto-renal bypass.

- Perioperative mortality: 2.1 to 6.1%.

- Early graft failure: 1.4 to 10%, usually due to thrombosis.

3. Percutaneous Intervention

Renal Artery Stenosis

Balloon angioplasty with or without stenting

· This is the treatment of choice for patients with fibromuscular dysplasia and uncontrolled hypertension despite aggressive drug therapy.

· It is successful in 82 to 100% of patients. Stenosis reoccurs in 10 to 11%.

· It is less effective for atherosclerotic RAS because of the potential for dissection and elastic recoil with restenosis rate in 10 to 47% after renal angioplasty.

Comments on Revascularization

- Hypertension is more likely to be cured after revascularization in patients with fibromuscular dysplasia than in patients with atherosclerotic RAS (60% vs < 30%), regardless of the type of revascularization.

- No significant difference in outcomes between angioplasty and medical therapy in the majority.

- Indications for revascularization: (see flow chart)

1. Unilateral RAS with asymmetric blood flow.

2. Refractory hypertension with fibromuscular dysplasia.

3. Bilateral RAS with impaired renal function.

Summary of Treatment of Renovascular Hypertension (Canadian Recommendations—2001)

1. Renal Artery Stenosis

2. Renovascular hypertension should be treated in the same manner as essential hypertension, except for caution in the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists, due to the risk of acute renal failure in bilateral disease or unilateral disease with a solitary kidney.

3. Close follow-up and early intervention (angioplasty and stenting or surgery) should be considered for patients with the following: uncontrolled hypertension despite therapy with three or more drugs; deteriorating renal function; bilateral atherosclerotic renal artery lesions (or tight atherosclerotic stenosis in a single kidney); or recurrent episodes of flash pulmonary edema.