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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), and diabetes mellitus.

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. The obstruction typically causes mid- to distal lesions of the renal artery. Angiographically, a multifocal dysplasia with a "string-of-beads" appearance is characteristic.

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

Clinical suspicion should arise particularly in patients with new-onset or resistant hypertension, hypertensive crises, an abdominal bruit, otherwise unexplained deterioration of renal function, an increase in serum creatinine after initiation of ACE inhibitor or angiotensin receptor blocker therapy, asymmetric kidney size, or recurrent flash pulmonary edema or otherwise unexplained episodes of heart failure.

Diagnostic workup in Renal Artery Stenosis

Laboratory Investigations in Renal Artery Stenosis

Serum creatinine, eGFR, and electrolytes to assess renal function. Urinalysis: mild proteinuria may be present.

Renal Doppler Sonography

Doppler sonography of the renal arteries including measurement of peak systolic velocity (PSV), end-diastolic velocity (EDV), the renal-aortic ratio (RAR), and the resistive index (RI). Indirect intrarenal signs include the tardus-parvus pattern, characterized by a prolonged systolic upstroke (acceleration) and low peak systolic velocity. Advantages of Doppler sonography for diagnosing renal artery stenosis include its non-invasive nature, low cost, and the feasibility of performing the exam while the patient is on antihypertensive medication. However, its accuracy is operator-dependent and can be limited by obesity, overlying bowel gas, or unfavorable vascular anatomy

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.

CT Angiography:

CT angiography is a highly reliable noninvasive method for the morphologic diagnosis of renal artery stenosis and also provides good visualization of calcifications, vascular anatomy, and accessory renal arteries. Disadvantages include ionizing radiation and iodinated contrast medium, so the indication should be considered carefully in patients with advanced renal insufficiency.

MRI Angiography:

MR angiography is a good alternative to CT angiography, particularly when iodinated contrast medium should be avoided. However, it is limited in the assessment of smaller branch vessels, by motion artifacts, and in patients with certain implants.

Digital subtraction angiography (DSA):

DSA is the reference method for definitive anatomic and hemodynamic assessment of renal artery stenosis and is used in cases of inconclusive noninvasive findings or before planned revascularization. Its advantage is the ability to perform simultaneous pressure gradient measurement and intervention. Disadvantages include its invasive nature, the risk of embolization, dissection, and bleeding, as well as contrast medium exposure.

Renal scintigraphy with Captopril Challenge Test

Captopril scintigraphy plays only a minor role in modern diagnostics. 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 IV 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.

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

Medical Therapy of Renal Artery Stenosis

Medical therapy is the cornerstone of treatment for atherosclerotic renal artery stenosis. The goals are control of arterial hypertension, reduction of cardiovascular risk, and stabilization of renal function. Treatment particularly includes ACE inhibitors or angiotensin receptor blockers, calcium channel blockers, diuretics, beta-blockers, statins, and antiplatelet therapy according to the overall vascular risk profile.

Indications for Surgical Therapy

Invasive treatment of renal artery stenosis (percutaneous transluminal angioplasty or open vascular surgery) is indicated in patients with ischemic nephropathy requiring intervention or with insufficient medical control of renovascular hypertension. Intervention is particularly indicated in patients with a solitary kidney or bilateral disease because of the high risk of renal insufficiency.

Endovascular Therapy (Percutaneous Transluminal Angioplasty)

Percutaneous transluminal angioplasty (PTA) can be performed directly after angiography (DSA). In fibromuscular dysplasia, a stent is usually not used. In atherosclerotic renal artery stenosis, primary stent placement is recommended.

Results: Randomized trials in atherosclerotic renal artery stenosis have not shown a general benefit of routine stent placement in addition to modern medical therapy with regard to hard renal or cardiovascular endpoints in unselected patients. The decision to intervene should therefore be individualized and based primarily on high-risk clinical constellations.

Complications: Possible complications include access-site complications, contrast-associated deterioration of renal function, cholesterol embolization, dissection, thrombosis, restenosis, and, rarely, renal infarction or retroperitoneal hemorrhage.

Open Vascular Surgery for Renal Artery Stenosis

Open vascular surgery is indicated when relevant concomitant disease is present, such as an aneurysm, when PTA is technically not feasible, or in the event of complications of PTA.

Aortorenal (Anatomic) Bypass Operation:

Endarterectomy or an interposition graft (vascular prosthesis, saphenous vein, or internal iliac artery) is used to replace the renal artery. An aortorenal bypass is not feasible in the presence of significant atherosclerosis or an abdominal aortic aneurysm.

Extra-anatomic Bypass Operation:

Alternatives to an anatomic bypass include, for example, a splenorenal bypass on the left and a hepatorenal bypass on the right.

Results:

Open surgical revascularization can be durably successful in selected cases, but it is more invasive than endovascular therapy and is associated with a higher perioperative risk. It is therefore used only selectively today.

Prognosis of Renal Artery Stenosis

The prognosis of atherosclerotic renovascular disease is determined largely by systemic atherosclerosis and the overall cardiovascular risk profile. In advanced ischemic nephropathy, the long-term prognosis is poor.

References

Bhalla V, Textor SC, Beckman JA, Casanegra AI, Cooper CJ, Kim ESH, Luther JM, Misra S, Oderich GS; American Heart Association Council on the Kidney in Cardiovascular Disease; Council on Hypertension; Council on Peripheral Vascular Disease; and Council on Cardiovascular Radiology and Intervention. Revascularization for Renovascular Disease: A Scientific Statement From the American Heart Association. Hypertension. 2022 Aug;79(8):e128-e143. doi: 10.1161/HYP.0000000000000217.

Gornik HL, Persu A, Adlam D, Aparicio LS, Azizi M, Boulanger M, Bruno RM, De Leeuw P, Fendrikova-Mahlay N, Froehlich J, Ganesh SK, Gray BH, Jamison C, Januszewicz A, Jeunemaitre X, Kadian-Dodov D, Kim ESH, Kovacic JC, Mace P, Morganti A, Sharma A, Southerland AM, Touzé E, Van der Niepen P, Wang J, Weinberg I, Wilson S, Olin JW, Plouin PF; Working Group ‘Hypertension and the Kidney’ of the European Society of Hypertension (ESH) and the Society for Vascular Medicine (SVM). First international consensus on the diagnosis and management of fibromuscular dysplasia. J Hypertens. 2019 Feb;37(2):229-252. doi: 10.1097/HJH.0000000000002019.

Sarafidis PA, Theodorakopoulou M, Ortiz A, Fernandez-Fernández B, Nistor I, Schmieder R, Arici M, Saratzis A, Van der Niepen P, Halimi JM, Kreutz R, Januszewicz A, Persu A, Cozzolino M. Atherosclerotic renovascular disease: a clinical practice document by the European Renal Best Practice (ERBP) board of the European Renal Association (ERA) and the Working Group Hypertension and the Kidney of the European Society of Hypertension (ESH). Nephrol Dial Transplant. 2023 Nov 30;38(12):2835-2850. doi: 10.1093/ndt/gfad095.

  Deutsche Version: Nierenarterienstenose

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