Etiology and Pathophysiology
Renal artery stenosis (RAS) is often caused by atherosclerosis or fibromuscular dysplasia. Other less common etiologies include vasculitis, neurofibromatosis, external compression, trauma, and damage following radiation exposure. The overall prevalence of renal artery stenosis in the general population is relatively low, but the incidence increases with age and is significantly higher among individuals with resistant hypertension. Atherosclerosis is the most common cause of renal artery stenosis, accounting for approximately 90% of cases. It predominantly occurs in elderly individuals and those with cardiovascular risk factors. Atherosclerotic renal artery stenosis is an important cause of secondary hypertension and is associated with increased morbidity and mortality due to cardiovascular events. The stenosis typically involves the ostium or the proximal 1/3 of the renal artery.
In contrast, fibromuscular dysplasia (FMD) is a less frequent cause of renal artery stenosis and is primarily seen in relatively younger individuals who lack cardiovascular risk factors. Renal artery stenosis caused by fibromuscular dysplasia often involves the middle or distal segment of the renal artery. Importantly, FMD-related stenosis has a higher success rate of curative intervention via renal artery revascularization, making accurate diagnosis particularly significant.
Renal artery stenosis commonly leads to renovascular hypertension as a result of renal ischemia, which triggers renin secretion and subsequent activation of the renin-angiotensin-aldosterone system (RAAS). This contributes to peripheral vasoconstriction and water/sodium retention. Atherosclerotic renal artery stenosis can also result in ischemic nephropathy, where ischemia in the affected kidney leads to glomerulosclerosis, tubular atrophy, and interstitial fibrosis, which can progressively advance to chronic kidney failure. Although FMD-induced renal artery stenosis also causes significant hemodynamic changes in renal blood flow, renal dysfunction is less common due to the absence of atherosclerosis-related cardiovascular risk factors.
Clinical Manifestations
The primary clinical features of renal artery stenosis arise from renovascular hypertension and ischemic nephropathy. Renovascular hypertension typically manifests as resistant hypertension that responds poorly to high doses or combinations of antihypertensive medications. Ischemic nephropathy, which may or may not be accompanied by renovascular hypertension, is characterized by a slow and progressive decline in renal function. Renal tubules are particularly sensitive to ischemia, and functional impairment often occurs initially, manifesting as nocturia, reduced urine specific gravity, and diminished urine osmolality, which indicate impaired concentrating ability of the distal tubules. Subsequently, a decline in glomerular filtration rate (GFR) occurs. Urinalysis may reveal minimal findings, including mild proteinuria, a small number of red blood cells, and occasional casts. In advanced stages, renal size is reduced, with asymmetry between the two kidneys reflecting the degree of stenosis in each renal artery.
Atherosclerosis-related stenosis is often accompanied by signs of atherosclerosis affecting other vascular systems, such as acute coronary syndrome, stroke, or peripheral arterial disease. For patients with atherosclerotic renal artery stenosis who might benefit from revascularization, screening with Doppler ultrasonography, CT angiography, or MR angiography can be considered.
Patients with fibromuscular dysplasia may report headache or pulsatile tinnitus. In younger patients, particularly women, presenting with newly diagnosed hypertension in the absence of other cardiovascular risk factors or a family history of hypertension, fibromuscular dysplasia should be considered as a differential diagnosis. Screening with renal artery Doppler ultrasonography is recommended in such cases. Since patients with FMD-induced renal artery stenosis often benefit from revascularization, further imaging with renal angiography is warranted if Doppler ultrasonography suggests stenosis.
Diagnosis
The clinical manifestations of fibromuscular dysplasia-related renal artery stenosis are often alleviated through renal artery interventional treatment, making timely diagnosis crucial. For atherosclerotic renal artery stenosis, establishing a clear diagnosis primarily affects medication selection, as renal artery angioplasty may offer minimal benefits.
Doppler ultrasound can assess renal artery conditions and measure blood flow velocity. A peak systolic velocity of the renal artery exceeding 180 cm/s suggests renal artery stenosis, making it an excellent screening tool for fibromuscular dysplasia. However, the reliability of this examination can be significantly affected by the experience of the sonographer, patient body type, and intestinal gas.
Multidetector CT angiography provides a rapid diagnostic tool for renal artery stenosis, with a sensitivity approaching 90% and specificity exceeding 90%. However, the use of iodinated contrast agents is limited in patients with reduced glomerular filtration rates, and significant vascular wall calcification may impair accurate estimation of stenosis severity.
Gadolinium-enhanced MR angiography can be used in patients with mild renal impairment, but it is contraindicated in those with severe renal dysfunction or end-stage renal disease due to the risk of nephrogenic systemic fibrosis. MR angiography is also susceptible to motion artifacts and has limited ability to detect distal renal artery stenosis caused by fibromuscular dysplasia.
Renal arteriography accurately reveals the location, extent, severity, and collateral circulation of renal artery stenosis, serving as the "gold standard" for diagnosis. However, due to the invasive nature of renal arteriography, it is typically reserved for cases where non-invasive tests fail to provide a definitive diagnosis.
Radionuclide imaging (including captopril renal scintigraphy), peripheral plasma renin activity (PRA) testing, and renal vein renin measurements can reflect the pathophysiological changes associated with renal artery stenosis to some extent. However, due to their poor sensitivity and specificity, these tests are not suitable as initial examinations for suspected cases and are only useful in select clinical situations.
Treatment
Fibromuscular Dysplasia-Related Renal Artery Stenosis
Percutaneous transluminal balloon angioplasty is the preferred treatment for fibromuscular dysplasia-related renal artery stenosis. Even for patients with well-controlled blood pressure, angioplasty is often performed to prevent the progression of stenosis to complete renal artery occlusion. The rate of restenosis after angioplasty is relatively low, and stent placement is usually unnecessary.
After angioplasty, blood pressure should be closely monitored, and renal function should be assessed every 3–4 months. Approximately 50% of patients experience improved blood pressure control following the procedure. For patients with persistent hypertension, ACE inhibitors or ARBs are recommended.
Atherosclerotic Renal Artery Stenosis
Treatment for atherosclerotic renal artery stenosis primarily relies on medication, with careful management of risk factors such as blood pressure, lipid levels, and blood glucose. Low-dose aspirin and statin therapy may provide benefits for these patients.
Antihypertensive therapy should include ACE inhibitors or ARBs. These medications are generally well-tolerated, but serum creatinine levels and eGFR should be carefully monitored during initial treatment or dose escalation. A significant increase in serum creatinine or a rapid decline in eGFR may indicate bilateral renal artery stenosis or stenosis in a solitary functioning kidney, in which case ACE inhibitors and ARBs should be discontinued, and renal artery angioplasty should be considered.
To date, randomized controlled trials (RCTs) on angioplasty for atherosclerotic renal artery stenosis have not demonstrated superiority over intensive medical therapy in terms of blood pressure control, reduction in antihypertensive medication use, improvement in renal function, reduction in cardiovascular events, or overall mortality. However, certain patients, such as those with refractory severe hypertension unresponsive to medical therapy, rapid renal function decline following ACE inhibitor or ARB use, or recurrent episodes of acute pulmonary edema without other identifiable causes, may derive clinical benefits from renal artery angioplasty.