INTRODUCTION
Renal artery stenosis (RAS) is a major cause of secondary hypertension and renal impairment [1-3]. Atherosclerosis is the most common etiology for RAS and usually involves the ostium and proximal artery [1]. This disease entity is a kind of inflammation that occurs when atherosclerotic plaques build up on the inside walls of the arteries [4,5]. The plaque is a sticky substance composed of fat, cholesterol, calcium, and other materials. As plaque accumulation increases, the arteries become hard and narrowed [4,5]. Accordingly, the early-stage of RAS is not clear on imaging examination, and visualization is achieved starting in the intermediate stage. At these stages, the size and shape of RAS are changeable according to the systolic and diastolic phases of heart beats. However, the size and shape of RAS are fixed regardless of heartbeat at the late-stage of RAS due to fibrosis.
Renal artery ultrasound (RAUS) shows high sensitivity for detecting RAS, but specificity is relatively low [6-11]. In addition, the detection ability of RAUS differs from that of arteriography. There has been no report demonstrating the cause of discrepancy between RAUS and arteriography. Moreover, because vascular intervention is limited in improving renal function in the late-stage of RAS [12-14], earlier detection is necessary for management.
Based on experience with numerous RAS cases, RAS does not occur in a single step but is a multi-step inflammatory disease. It is hypothesized that RAS sonographically consists of early, intermediate, and late stages according to the degree of atherosclerotic change. Accordingly, RAUS can show various imaging features according to disease stage.
From this point of view, we can hypothesize that RAUS can depict imaging features of RAS stages. There are rare studies reporting RAUS findings of each RAS stage. The purpose of this review is to introduce a hypothesis on the stages of RAS, to show the features of each stage, and to compare RAUS and angiography in terms of detecting RAS stages.
EARLY-STAGE RAS
At early-stage RAS, stenosis begins to be seen at the diastolic phase of the heartbeat (Table 1). At this stage, atherosclerotic inflammation has not hardened and narrowed the intima of a renal artery. Because the RAS does not restrict the diameter of the artery at the systolic blood pressure, stenosis is not seen at the systolic phase. Therefore, RAS is seen only at diastolic phase because it begins to appear at low blood pressure of diastolic phase. Early-stage RAS also does not show high-speed blood flow through a stenotic lumen or post-stenotic turbulence flow. Accordingly, post-stenotic dilatation is minimal at this stage of RAS. Because renal ischemia is minimal, patients with early-stage RAS commonly are asymptomatic.
The early stage of RAS is difficult to detect because of its limited visualization only on diagnostic phase. To overcome this, RAUS is a suitable imaging modality because it can provide real-time imaging of diastolic phase as well as systolic phase. On color Doppler RAUS, a renal artery can be unremarkable at systolic phase but is narrowed on diastolic phase (Fig. 1). However, there is no sign of RAS on gray-scale or spectral Doppler RAUS.
Renal ultrasound (US) cannot detect the early-stage of RAS reliably, showing poor intra- and inter-observer agreement [15,16]. Transient and reversible narrowing of a renal artery at diastolic phase alone has minimal influence on intra-renal arterial hemodynamics. The ability of renal arteriography has not been reported in detecting early-stage RAS but seems to be poor due to markedly poor sensitivity (Table 2). However, further investigation is necessary to explain why early-stage RAS is difficult to depict with arteriography.
INTERMEDIATE-STAGE RAS
Intermediate-stage RAS is defined when a stenosis becomes visible on RAUS at systolic phase as well as at diastolic phase (Table 1). Development of atherosclerotic fibrosis at this stage can start to harden the wall of a renal artery. Accordingly, RAS can be visualized at systolic phase but is more apparent than at diastolic phase. The degree of RAS at diastolic phase progresses at the intermediate stage compared to that of the early stage. Post-stenotic dilatation begins to develop because of the turbulence caused by the high-speed of blood flow through the stenotic portion. Renal ischemia is more apparent at the intermediate stage, and renal function begins to decrease and blood pressure begins to increase. Patients with intermediate-stage RAS start to be symptomatic.
RAUS shows mild to moderate stenosis at systolic phase as well as at diastolic phase (Fig. 2). Color Doppler RAUS shows fast blood flow through the narrow lumen of the renal artery. Spectral Doppler US shows an increase in the systolic velocity of blood flow in RAS, although it barely exceeds 180 to 200 cm/sec [3,6,7,17,18]. In patients with unilateral intermediate-stage RAS, an involved artery experience higher velocity of blood flow than a non-involved artery. Contrast-enhanced RAUS also shows mild to moderate stenosis at systolic phase and moderate stenosis at diastolic phase.
Arteriography has relatively low sensitivity at intermediate-stage disease because of the mild stenosis compared to that at late-stage RAS (Table 2). Thus, it is not uncommon that arteriography is negative for intermediate-stage RAS even though RAUS is positive. Moreover, because renal artery catheterization hinders narrowing at systolic phase, it decreases the sensitivity for detecting intermediate RAS. Clinically, patients with intermediate RAS becomes symptomatic due to increased renal ischemia. Therefore, detecting RAS at the intermediate stage is very important for determining treatment planning. Early medication or intervention helps to improve treatment outcomes of RAS, when renal function still remains reversible. Radiologists should be aware that intermediate-stage RAS is not visible on arteriography but can be visualized on RAUS. Close observation or early treatment should be considered if RAUS is positive but arteriography is negative in patients with clinical suspicion of RAS.
LATE-STAGE RAS
Late-stage RAS is defined when stenosis is clearly seen at the same degree regardless of heartbeats (Table 1). At this stage, the degree of RAS is more severe than that at the intermediate stage and is the same at diastolic and systolic phases. Because atherosclerotic inflammation has progressed to near fibrosis, the wall of a renal artery is so hard or rigid. Post-stenotic dilatation at this stage is greater than that at the intermediate stage because of greater impact of the turbulent flow caused by the severe stenosis. Patients with late-stage RAS are symptomatic, experiencing poor renal function and uncontrolled hypertension [2,19].
Gray-scale RAUS can show RAS if the sonic window is suitable. Color Doppler US shows bright color-coded blood flow through the stenosis and turbulent flow in post-stenotic dilatation. Spectral Doppler US shows that the velocity of blood flow exceeds 180 to 200 cm/sec within the stenosis [3,6,7,17,18]. A reno-aorta ratio of peak systolic velocity of 3.5 or greater is another good indicator of RAS [8,9,11]. High velocities and multi-directions of turbulence flow are easily identified within post-stenotic dilatation. Contrast-enhanced RAUS shows the same findings of late-stage stenosis as well as does arteriography. US angiography can be called as computed tomography or magnetic resonance angiography. When a kidney comes to the end-stage disease, blood flow demand decreases because the kidney shrinks with irreversible renal damage. Thus, end-stage RAS becomes lower velocity of blood flow.Subsequently, the kidney size becomes markedly decreased and the cortical echogenicity becomes markedly increased.
Arteriography clearly shows the difference between late-stage RAS and intermediate-stage RAS (Table 2). Prior to intervention, radiologists and clinicians should be familiar with RAUS findings to determine kidney function. Re-hyperperfusion can facilitate renal damage in patients with late-stage RAS even if the internal diameter of an renal artery increases with angioplasty or stenting (Fig. 3) [12-14].
CONCLUSION
Atherosclerotic RAS is a multi-stage inflammatory process involving renal artery and consists of early, intermediate, and late stages. RAUS is useful in depicting characteristic imaging features according to each stage. Intermediate-stage RAS is positive on RAUS but frequently negative on arteriography. Detecting RAS prior to the late stage is of great importance in improving treatment outcome.
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