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Diagnosis and Therapy of Renal Artery Stenosis

Definition of Renal Artery Stenosis

Renal artery stenosis is the narrowing of the renal artery, leading to renal arterial hypertension, ischemic nephropathy, and end-stage renal disease (ESRD) (Safian and Textor, 2001) (Textor and Wilcox, 2001).

Epidemiology of Renal Artery Stenosis

20–40% of patients with atherosclerosis (peripheral arterial disease, aortic aneurysm, or coronary heart disease, usually over 50 years old) have also a significant renal artery stenosis. Ischemic nephropathy due to renal artery stenosis is the cause of terminal renal failure in 14% of patients over 60 years requiring dialysis. Fibromuscular dysplasia is seldom the cause of renal artery stenosis, predominantly in younger patients and women.

Etiology and Pathology of Renal Artery Stenosis

Renal Artery Stenosis due to Atherosclerosis

Arteriosclerosis is the predominant etiology (90%) of renal artery stenosis, mainly affecting the proximal part of the renal artery. The obstruction is caused by eccentric plaques, which narrow the lumen and may lead to dissection or thrombosis with complete vessel occlusion.

Risk factors of atherosclerosis: hyperlipidemia, hypertension, smoking, male gender, genetics (familiar risk factors), diabetes mellitus, hyperuricemia.

Renal Artery Stenosis due to Fibromuscular Dysplasia

There are different pathological forms of fibromuscular dysplasia: medial and perimedial fibroplasia mainly in women aged 25–50 years and intimal manifestation mainly in children.

Other causes of renal artery stenosis:

Aneurysm, neurofibromatosis, middle aortic syndrome (a form of Takayasu arteritis), extrinsic obstruction caused by tumors, irradiation effects and inflammation.

Pathophysiology of Renal Artery Stenosis

Renal artery stenosis leads to the activation of the renin-angiotensin-aldosterone system (RAAS), ischemia of the kidney, and renal arterial hypertension.

Signs and Symptoms of Renal Artery Stenosis

Arterial hypertension and the following clinical risk factors suggest renal hypertension due to renal artery stenosis: hypokalemia (without diuretics), elevated creatinine concentration or cystatin C, abdominal stenotic bruit, severe hypertension with hypertensive crises, arteriosclerosis in other organs and unilateral atrophic kidney.

Diagnostic workup in Renal Artery Stenosis

Laboratory Investigations in Renal Artery Stenosis

• Hypokalemia (in 20%)
• Elevated creatinine concentration
• Elevated renin concentration (80% sensitivity and specificity if antihypertensive medication was paused)
• Urine analysis: mild proteinuria

Renal Doppler Sonography

Doppler sonography of the renal artery with detection of the renal artery flow rates, renal-aortic ratio (RAR), and resistive index (RI). The benefits of ultrasound imaging for diagnosing renal artery stenosis are the lack of invasiveness, low costs, and no need for pausing the antihypertensive medication. Renal Doppler sonography misses the diagnosis (false negative) in 10–20%.

Flow rates of the renal artery:

The normal value for the peak systolic velocity (PSV) is 80–150 cm/s, and 20–50 cm/s for the end-diastolic velocity (EDV). Renal artery stenosis increases PSV and EDV. A PSV of >180 cm/s and an EDV of >80 cm/s speak in favor of renal artery stenosis.

Reno-aortic ratio:

The reno-aortic ratio is calculated from the quotient of renal PSV and aortic PSV. A reno-aortic ratio (RAR) >3.5 is typical for renal artery stenosis (if a normal flow in the aorta is present).

Resistive index:

An RI below 0.5 indicates significant renal artery stenosis, but this is not sufficient as the sole diagnostic criterion. A resistive index (RI) >80% is predictive for severe organ damage; and blood pressure improvement after endovascular intervention or revascularization is not likely.

Captopril Challenge Test

ACE inhibitors must be paused for one week. In renal artery stenosis, the captopril challenge test leads to a significant increase of renin one hour after 25 mg captopril p.o. The test has a low sensitivity, but high specificity and is therefore appropriate to exclude or confirm a renal artery stenosis.

Renal scintigraphy with Captopril Challenge Test

ACE inhibitors must be paused for one week. Renal scintigraphy is done before and one hour after administration of captopril 25 mg p.o. or enalapril 0.04 mg/kg i.v. Pathological findings include unilateral or bilateral decreased renal function compared to baseline, differences in size as a sign of an atrophic kidney, delayed maximal secretion and cortical retention of the radionuclide. The test has a 90% sensitivity and specificity for the presence of a hemodynamically significant renal artery stenosis.

Spiral CT Angiography:

Imaging of the renal artery with a spiral CT scan is an alternative to invasive angiography. Disadvantages: side effects of the contrast medium, and stenoses in smaller arteries cannot be identified.

MRI Angiography:

MRI imaging is an alternative to invasive angiography; it avoids radiation exposure or iodine-containing contrast agent. Disadvantages: contraindicated if metal implants are present, stenoses in smaller arteries cannot be identified, and expensive.

Digital subtraction angiography (DSA):

Invasive angiography is the gold standard of renal artery stenosis imaging. Concomitant therapy (PTA) is also possible. Disadvantages: invasiveness (hematoma, embolism, thrombosis, dissection), side effects of the contrast medium, and high costs.

Percutaneous Renal Biopsy:

Renal biopsy reveals the extent of ischemic renal damage due to renal artery stenosis and may predict the therapeutic success of revascularization.

Intravenous Pyelography

Intravenous pyelography is no longer used for the diagnosis of renal artery stenosis. IVP signs of renal artery stenosis are a renal size difference of more than 1.5 cm, delayed contrasting of the kidney (delayed renal blush) and delayed elimination of the contrast medium in early X-ray films.

Differential Diagnosis of Renal Artery Stenosis

Page Kidney:

The compression of the kidney by a retroperitoneal hemorrhage, retroperitoneal tumor or renal cyst may release renin and lead to renal hypertension.

Chronic Pyelonephritis:

Renal scars of chronic pyelonephritis may lead to ischemic areas of the cortex, renin release, and to renal hypertension.

Rarities:

Congenital hypoplasia or dysplasia, radiation injury of the kidney, renin-producing tumors (renal cell carcinoma, Wilms tumor).

Treatment of Renal Artery Stenosis

Pharmacotherapy of Renal Artery Stenosis

The goal of medical treatment of renal artery stenosis is the control of hypertension with beta-blockers, diuretics and ACE inhibitors. ACE inhibitors are, however, contraindicated in bilateral renal artery stenosis or renal artery stenosis in a solitary kidney.

Indications for invasive Treatment of Renal Artery Stenosis

Invasive treatment of renal artery stenosis (percutaneous transluminal angioplasty or vascular surgery) is indicated for ischemic nephropathy requiring intervention or inadequate medical control of renal hypertension. An intervention is particularly indicated for a single kidney or bilateral involvement due to the high risk of renal failure.

Endovascular Treatment of Renal Artery Stenosis

Percutaneous transluminal angioplasty (PTA) may be done directly after invasive angiography. In the case of fibromuscular dysplasia, stent placement is often unnecessary. In atherosclerotic renal artery stenosis, primary stenting is recommended.

Results of PTA: to improve arterial hypertension: cure 5–23%, improvement in 30–70%, no improvement in 6–63%. Prevention of ischemic nephropathy after PTA: improved renal function in 15–43%, stable renal function in 26–50%.

Complications of PTA: mortality 1–2% , need for surgical intervention 5–20%. Restenosis in 5–20%. Hematoma at the punction side, femoral AV fistula, dissection, acute thrombosis, side effects of contrast medium, worsening of renal function due to renal infarction. Retroperitoneal hemorrhage.

Surgical Treatment of Renal Artery Stenosis

Vascular surgery is indicated in certain concomitant diseases (e.g., aneurysm), if PTA is technically not feasible or due to complications of PTA. The creatine concentration should be less than 4 mg/dl for a successful outcome.

Aortorenal (anatomical) bypass surgery:

Endarterectomy or aortorenal bypass with a free graft (vascular prosthesis, hypogastric artery, or saphenous vein). Aortorenal bypass surgery is impossible if severe arteriosclerosis or aneurysm of the aorta is present.

Extra-anatomical bypass surgery:

Alternatives to aortorenal bypass are splenorenal bypass (left side) oder hepatorenal bypass (right side). Prerequisite: Lateral angiography with the exclusion of significant stenosis of the celiac artery. If stenosis of the celiac artery is present, renal revascularization is possible using the thoracic aorta.

Results:

Arterial hypertension after revascularization: cure in 20–40%, improvement in 50–70%. Improvement of ischemic nephropathy after revascularization: improved renal function in 20–60%, stabilized renal function in 30–50%, and worsened renal function in 10–25%.

Complications of vascular surgery:

All risks of a laparotomy, kidney infarction, cardiac ischemia, cerebral ischemia, mortality 2–6%.

Prognosis of Renal Artery Stenosis

Renal artery stenosis due to arteriosclerosis is a progressive disease: in 50% of cases the obstruction progresses and 16% will suffer from complete closure. The greater the obstruction at initial diagnosis, the more likely the progression and the complete closure. If renal failure requires dialysis due to renal artery stenosis, the prognosis due to vascular complications is poor: median survival of 27 months, and the five-year survival rate is 12%.

References

Safian und Textor 2001 SAFIAN, R. D. ; TEXTOR, S. C.: Renal-artery stenosis.
In: N Engl J Med
344 (2001), Nr. 6, S. 431–42

Textor und Wilcox 2001 TEXTOR, S. C. ; WILCOX, C. S.: Renal artery stenosis: a common, treatable cause of renal failure?
In: Annu Rev Med
52 (2001), S. 421–42

  Deutsche Version: Nierenarterienstenose