The role of Doppler ultrasonography in the detection and management of nutcracker syndrome
Article information
Abstract
Nutcracker syndrome is caused by the compression of the left renal vein between the abdominal aorta and the superior mesenteric artery. The use of Doppler ultrasonography to diagnose this condition is challenging due to the dynamic nature of the nutcracker phenomenon and the variability of its symptoms, which can fluctuate with changes in patient posture and respiration. This review emphasizes the critical role of Doppler ultrasonography in identifying and managing nutcracker syndrome. It also explores the various subtypes of the nutcracker phenomenon and discusses how Doppler ultrasonography can improve patient outcomes by enabling management strategies that are informed by dynamic assessments of left renal vein compression.
Introduction
The detection of nutcracker phenomenon (NCP) and the diagnosis of nutcracker syndrome (NCS) using Doppler ultrasonography (US) pose significant challenges, despite the relatively high prevalence of these conditions [1-3]. These difficulties stem from limited knowledge, interest, and experience in the use of Doppler US for NCP and in correlating Doppler US findings with the clinical symptoms and signs of NCS.
It is crucial to distinguish between the terms NCP and NCS, as they refer to different concepts. NCP describes an abnormal compression of the left renal vein (LRV) between the abdominal aorta (AA) and the superior mesenteric artery (SMA). The term NCS is used when this compression is associated with hematuria, proteinuria, left flank pain, discomfort in other abdominal areas, or various bladder symptoms, and no other causes for these symptoms or signs can be identified [1-4].
Importantly, NCP is not a static condition; it is dynamic and varies with changes in the patient's posture and respiration. Doppler US proves to be a valuable tool in evaluating NCP as it allows for the assessment of LRV compression and provides real-time observation of how this compression changes with the patient's posture. This dynamic assessment is particularly useful as it helps patients with NCS understand the fluctuating nature of their symptoms and the importance of avoiding the supine sleeping position. It is well understood that compression of the LRV is greatest in the supine position and can be alleviated in lateral decubitus positions. Typically, compression is less severe in the left lateral decubitus (LLD) position than in the right lateral decubitus (RLD) due to the liver's position on the right side. Demonstrating the varying degrees of LRV compression and corresponding flow velocities in the supine, LLD, and RLD positions can help NCS patients comprehend why the LLD position is optimal for sleeping.
This review article aims to guide physicians in effectively using Doppler US to evaluate NCP and manage patients with NCS.
History and Definition of NCP and NCS
The first description of LRV entrapment was published in 1950 by ElSadr and Mina [5]. In 1971, Chait et al. [6] compared the anatomical arrangement of the AA and SMA to the arms of a nutcracker. The term NCS was subsequently introduced by de Schepper in 1972 to describe this condition (Fig. 1) [7,8]. The natural positioning of the LRV between the AA and SMA typically results in some degree of compression by these pulsating arteries and mild dilatation of the proximal hilar LRV (h-LRV), which is generally considered normal [9,10]. However, NCP refers to excessive compression of the LRV between these arteries. When unexplained symptoms and signs accompany NCP, the condition is diagnosed as NCS.
A photograph of Dr. Arthur M. De Schepper (1937- 2013), Professor Emeritus, University of Antwerp, Belgium, who published a historical article, "Nutcracker phenomenon of the renal vein and venous pathology of the LK".
Reprinted from Parizel PM, Bosmans JM. J Belg Soc Radiol 2013;96:329-330, according to Creative Commons License [8].
Typical symptoms of this condition include hematuria, proteinuria, and left flank pain. Hematuria and left flank pain are commonly caused by LRV hypertension and congestion of the left kidney. The mechanism behind proteinuria is not well established, but it is thought to result from increased protein filtration due to altered glomerular microcirculation caused by LRV hypertension [11]. However, patients with NCS may also exhibit atypical symptoms such as abdominal pain or discomfort in various locations, bladder symptoms, or fluctuations in the glomerular filtration rate [12-17]. These atypical symptoms could be linked to LRV hypertension and the development of collateral vessels. While various symptoms may be associated with NCS, establishing a clear cause-and-effect relationship is often challenging. If symptoms improve with the avoidance of a supine sleeping posture, they may be attributed to NCP (Fig. 2).
A 35-year-old man who presented wi th lef t f lank pain.
A grayscale ultrasonography (US) image (left) and a color Doppler US image (right) of the left renal vein (LRV) reveal narrowing of the aortomesenteric segment of the LRV (arrow) and jetting flow with color aliasing (arrowheads), indicative of nutcracker phenomenon (NCP). Spectral Doppler US of the am-LRV shows a peak flow velocity of 150 cm/s (not shown). His left flank pain was suspected to be caused by NCP, and he was advised to change his usual sleeping posture from supine to left lateral decubitus. After a week, his left flank pain completely resolved, supporting a clinical diagnosis of nutcracker syndrome with left flank pain. a, abdominal aorta; s, superior mesenteric artery.
Prevalence of NCP and NCS
The exact prevalence of NCP and NCS remains unknown, although there is growing evidence that NCS may have been underreported previously [3,18-20]. NCS is classified as a rare disease by the Genetic and Rare Disease (GARD) Information Center of the National Institutes of Health and the Orphanet portal, which focuses on rare diseases and orphan drugs. This misunderstanding largely arises from the diagnostic approach, which typically involves invasive catheterization and pressure measurement of the LRV in patients presenting with gross hematuria. According to the GARD Information Center, the uncertainty regarding the exact prevalence of NCS is partly due to the lack of standardized diagnostic criteria and the variability of symptoms among affected individuals.
Recent data from our specialized kidney clinic have provided new insights into this issue. In a study involving 1,223 consecutive patients who underwent Doppler US of the LRV, using a peak flow velocity (PFV) exceeding 100 cm/s as a criterion for NCP, we found that the prevalence of NCP and NCS was approximately 30% and 15%, respectively [3]. It is important to note that these data were collected from patients attending the specialized kidney clinic, rather than from the general population. Consequently, the reported prevalence rates of NCP and NCS (30% and 15%) may be overestimated due to selection bias. This finding highlights the potential under-recognition of NCS and underscores the importance of accurate diagnosis and management in clinical practice. As awareness increases and diagnostic tools improve, we anticipate a better understanding and enhanced management of this condition in the future.
Diagnostic Techniques and Criteria of NCP and NCS
Traditionally, NCS was diagnosed in patients who presented with gross hematuria by using LRV catheterization and measuring the pressure gradient. However, this invasive method is no longer commonly employed. Nowadays, noninvasive techniques such as US are used to identify NCS by assessing various anatomical parameters, including the diameter of the LRV in both compressed and proximally dilated sections, as well as the angle between the AA and SMA. Despite these advancements, the measurement of these anatomical parameters has had limited success in distinguishing between patients and control groups due to significant overlap [2,21]. Both computed tomography and magnetic resonance imaging have been suggested as methods to detect NCP, but Doppler US remains the preferred technique because of its safety, simplicity, and ability to provide real-time observations.
More objective velocity data can be obtained by using Doppler US to evaluate LRV flow dynamics. Color Doppler US (CDUS) offers comprehensive velocity information through color-coded displays, which simplifies the scanning of the LRV and aids in identifying areas of high velocity. PFV can be measured with spectral Doppler US (SDUS) by positioning the sample volume in the areas of color aliasing within the LRV, as identified on CDUS.
Spectral Doppler Findings
Subtle compression at the aortomesenteric segment of the left renal vein (am-LRV) is a normal phenomenon, with a PFV ranging from 40-50 cm/s, compared to 10-20 cm/s in the non-compressed h-LRV. A PFV exceeding 100 cm/s at the compressed am-LRV serves as the most practical criterion for detecting NCP. Typically, normal Doppler spectra of the LRV demonstrate continuous, slightly pulsatile, antegrade flow into the inferior vena cava (IVC), with a PFV of 40-50 cm/s (Fig. 3). In patients with NCP, the Doppler spectra display varying degrees of pulsatility (Fig. 4), with PFVs commonly ranging from 100 cm/s to 200 cm/s. In cases of severe compression and limited collateral vessels, the PFV often surpasses 200 cm/s, and in rare instances, it may exceed 300 cm/s (Fig. 5). Doppler spectral tracing, performed while patients maintain quiet respiration, reveals respiratory changes characterized by higher PFV during expiration and lower PFV during inspiration. The highest PFV observed throughout the respiratory cycle is recorded as the PFV for the examination (Fig. 6).
Normal Doppler spectrum ofthe left renal vein.
Spectral Doppler ultrasonography of the aortomesenteric segment of the left renal vein in a 80-year-old asymptomatic woman, demonstrating continuous antegrade flow into the inferior vena cava with a normal peak flow velocity of 48.7 cm/s.
Doppler spectral patterns of the aortomesenteric segment of the left renal vein (am-LRV) in nutcracker phenomenon.
These patterns are variable, typically displaying two patterns: a spiky pulsatile pattern and a flat continuous pattern. A. A 43-year-old man presented with microscopic hematuria and proteinuria. Spectral Doppler ultrasonography (SDUS) of the am-LRV shows a spiky pulsatile pattern in Doppler spectra, with a peak flow velocity (PFV) of 138 cm/s. B. A 50-year-old woman presented with microscopic hematuria. SDUS of the am-LRV shows a flat continuous pattern in Doppler spectra, with a PFV of 133 cm/s.
A very high peak flow velocity (PFV) in nutcracker phenomenon in a 70-year-old woman with left flank and epigastric pain, and foamy urine.
Spectral Doppler ultrasonography of the aortomesenteric segment of the left renal vein shows a very high PFV (308 cm/s).
A 64-year-old woman with vague low abdominal discomfort.
A. A spectral Doppler ultrasonography (SDUS) image of the aortomesenteric segment of the left renal vein (am-LRV) taken during normal breathing shows respiratory variations in flow velocity, with a peak flow velocity (PFV) of 181 cm/s. B, C. SDUS images of the am-LRV taken while the patient held their breath in expiration (B) and inspiration (C) demonstrate the difference in PFV. The PFV during expiration was significantly higher than during inspiration (249 cm/s vs. 114 cm/s).
The first study comparing PFV in the compressed am-LRV was conducted by the author of this review article in 1996 [17]. It included 16 adult NCS patients presenting with gross hematuria and 18 healthy adults. In the NCS patient group, the PFV in the am-LRV was measured at 110.7±35.8 cm/s, compared to 50.9±27.9 cm/s in the control group. There were no significant differences in PFV in the h-LRV between the NCS patients and the control group.
A similar result was reported in 2006 by the author’s colleagues, who are pediatric radiologists at the same hospital. They conducted a study involving 12 pediatric NCS patients and 20 controls [20]. In the pediatric NCS group, the PFV in the am-LRV was 139.6±31.0 cm/s, compared to 72.4±24.4 cm/s in the control group. Interestingly, the PFV in the am-LRV was slightly higher in the pediatric group than in the adult group.
Based on these studies, a straightforward and practical criterion for detecting NCP was established. In normal control groups, PFV typically ranged from 10 to 20 cm/s in the h-LRV and from 40 to 50 cm/s in the am-LRV (Fig. 3). A study comparing PFVs between the hilar and am-LRV reported a sensitivity of 80% and a specificity of 94% using a criterion of a PFV ratio greater than 5.0 [18]. However, for simplicity and practicality, a PFV exceeding 100 cm/s in the amLRV was adopted as the criterion for detecting NCP [2].
In the author’s early experience, to measure accurate velocity, it was preferable to employ grayscale US over CDUS and to use a narrow sample volume while patients held their breath. However, with increasing experience and the understanding that NCP is a dynamic phenomenon, the author now prefers using CDUS while patients maintain comfortable breathing. This approach facilitates real-time observation of color changes, aiding in the localization of the bright-colored jetting area of high flow velocity with aliasing color signals. Measuring PFV on SDUS with proper angle correction and a wide sample volume, typically 15-20 mm, is also feasible while patients breathe comfortably. Using a wide sample volume may inadvertently include vessels beyond the LRV, such as the right renal artery (RRA), superior mesenteric vein, or portal vein. To address this issue, we can repeat the SDUS with a smaller sample volume while the patient holds his or her breath. Typically, compression of the am-LRV is more severe during expiration than inspiration because the anterior-posterior dimension of the abdomen increases during inspiration. We may achieve a higher PFV when patients maintain normal breathing compared to when they hold their breath (Fig. 6). A complete Doppler US examination for the LRV can be performed without requiring patients to hold their breath, making the procedure more comfortable for both patients and examiners. Pre-examination fasting is necessary to minimize bowel gas anterior to the LRV.
Postural Variations of Doppler US Findings of the LRV
The degree of compression of the LRV in NCS varies depending on the patient's posture. It is most severe when the patient is lying on their back, less severe in a lateral decubitus position, and least severe in an LLD position. Doppler US effectively illustrates these variations in LRV compression as the patient changes posture, aiding in identifying optimal and detrimental sleeping positions for their condition (Fig. 7). By asking about the patient's typical sleeping posture, we can frequently correlate their symptoms with their sleeping habits, offering enhanced insights into the management of NCS.
A 69-year-old man with a fluctuating glomerular filtration rate showing postural variations of Doppler ultrasonography (US) findings.
A. A grayscale US image (left) and a color Doppler US (CDUS) image (right) of the left renal vein (LRV) in supine position show compression of the LRV between the abdominal aorta (AA) (a) and superior mesenteric artery (SMA) (s), with jetting flow with color aliasing (arrowheads). B. Spectral Doppler ultrasonography (SDUS) of the aortomesenteric segment of the left renal vein (am-LRV) in supine position shows a peak flow velocity (PFV) of 145 cm/s. C. A grayscale US image (left) and a CDUS image (right) of the LRV in a 45° left lateral decubitus (LLD) position show the SMA (s) slightly shifted to the left and less prominent compression of the LRV between the AA (a) and SMA (s). Note the absence of jetting flow with color aliasing in the LRV. D. SDUS of the am-LRV in a 45° LLD position shows a PFV of 87.1 cm/s. E. A grayscale US image (left) and a CDUS image (right) of the LRV in a 90° LLD position show that the SMA (s) has shifted further to the left and the inferior vena cava (v) has moved anteriorly. The LRV shows no signs of compression between the AA (a) and SMA (s). F. SDUS of the am-LRV in a 90° LLD position shows a PFV of 62.5 cm/s. G. A grayscale US image (left) and a CDUS image (right) of the LRV in a 45° right lateral decubitus (RLD) position show the SMA (s) has shifted back to the midline anterior to the AA (a) and the LRV (am-LRV) is once again compressed with color aliasing jetting flow (arrowheads). H. SDUS of the am-LRV in a 45° RLD position shows a PFV of 151 cm/s. I. A grayscale US image (left) and a CDUS image (right) of the LRV in a 90° RLD position show a narrow space between the AA (a) and SMA (s), resulting in more severe compression of the am-LRV, with color aliasing jetting flow (arrowheads) and sluggish flow in the proximal hilar LRV (asterisk). J. SDUS of the am-LRV in a 45° RLD position shows a PFV of 138 cm/s.
Other US Findings Associated with NCP
While grayscale US reveals anatomical changes in the LRV, such as luminal narrowing in the compressed am-LRV and dilatation in the proximal h-LRV, CDUS offers insights into blood flow dynamics. The presence of color aliasing in the compressed am-LRV indicates high-velocity jetting flow, which facilitates the placement of the sample volume in this area for Doppler spectra acquisition and PFV measurement. In the proximal dilated h-LRV, color signals may indicate either smooth antegrade flow (Fig. 8A) or slow and sluggish flow (Fig. 8B). Occasionally, the proximal h-LRV appears collapsed, with prominent collateral vessels visible in retroperitoneal areas. A dilated left gonadal vein can be seen in sagittal plane imaging, exhibiting regurgitant flow into the pelvic cavity (Fig. 9A). In these cases, CDUS of the pelvic cavity in the transverse plane illustrates the extent of pelvic congestion (Fig. 9B, C). Identifying pelvic congestion is straightforward when it is asymmetric; however, when it is bilateral, symmetric, and mild, recognition can be challenging. These diverse findings from grayscale and Doppler US provide crucial information that aids in understanding the flow dynamics of the LRV in patients with NCP and the symptoms of patients with NCS.
Nutcracker phenomenon (NCP) with smooth antegrade flow versus sluggish flow in hilar left renal vein (h-LRV).
A. A 34-year-old woman presented with microscopic hematuria, proteinuria, and urinary frequency. A grayscale ultrasonography (US) image (left) and a color Doppler US (CDUS) image (right) show narrowing of aortomesenteric segment of the left renal vein (am-LRV) with color aliasing jetting flow (arrows), indictive of NCP. A dilated proximal h-LRV (h) is filled with a homogeneous antegrade flow signals (asterisk) at CDUS. B. A 17-year-old man presented with proteinuria. A grayscale US image (left) and a CDUS image (right) demonstrate narrowing of the am-LRV with color aliasing jetting flow (arrows), indicative of NCP. The images also show a dilated proximal h-LRV (h) with absent flow signals (asterisk) on CDUS, suggesting sluggish flow. s, superior mesenteric artery; a, abdominal aorta.
A 52-year-old woman with proteinuria.
A. A parasagittal color Doppler ultrasonography (CDUS) image of the left abdomen reveals a tubular structure filled with color signals (arrows) connected to the left renal vein (LRV), indicating a dilated left gonadal vein with regurgitating blood flow from the LRV into the pelvis. B, C. Grayscale ultrasonography (B) and CDUS (C) images of the pelvic cavity in a transverse plane demonstrate tortuous, dilated vessels around the uterus, indicative of pelvic congestion.
Subtypes of NCP
The classical presentation of NCP involves the compression of the LRV in the narrow space between the AA and the SMA (Fig. 10). However, there are variations in how the LRV is compressed in other forms of NCP. In the second variation, the LRV is not significantly compressed between the AA and SMA. Instead, it is compressed distally to the am-LRV from the rear by the origin of the RRA, which emerges from the aorta in a somewhat anterior direction (Fig. 11). This specific pattern of LRV compression by the RRA has been documented previously [22,23] and is known as the anterolateral or lateral type [23]. The third variation of NCP involves the LRV being stretched anterior to the AA (Fig. 12). In this case, the LRV tightly drapes over the AA, a pattern often seen in patients with a prominent and tortuous AA. These variations of NCP can be categorized as follows: the classical compression of the LRV between the AA and the SMA as type 1, the compression of the LRV by the RRA as type 2, and the stretching of the LRV over the AA as type 3. Generally, the compression effect on the LRV in types 2 and 3 is less severe than in type 1 NCP. Additionally, a patient may display different features of NCP during respiration and in various postures.
A 37-year-old woman with microscopic hematuria showing type 1 nutcracker phenomenon (NCP).
A, B. Grayscale ultrasonography (US) (A) and color Doppler US (B) images of the left renal vein show compression of the aortomesenteric segment of the left renal vein (am-LRV; arrow) between the abdominal aorta (a) and superior mesenteric artery (s) indicative of type 1 NCP. Note the jetting flow with color aliasing (arrowheads) from the am-LRV into the inferior vena cava. Additionally, note the absent flow signal in the dilated hilar left renal vein, indicative of sluggish flow (asterisk).
A 64-year-old man with left flank pain showing type 2 nutcracker phenomenon (NCP).
A, B. Grayscale ultrasonography (US) (A) and color Doppler US (B) images of the left renal vein (LRV) demonstrate compression of the LRV not between the abdominal aorta (a) and superior mesenteric artery (s) but by the origin of the right renal artery (RRA) arrow in A indicative of type 2 NCP. Note the jetting flow with color aliasing (arrowheads) from the site where LRV is compressed posteriorly by the RRA origin arrow in B. Additionally, observe the homogeneous color signal in the dilated hilar left renal vein, indicating smooth antegrade flow (asterisk).
A 59-year-old woman with a fluctuating glomerular filtration rate showing type 3 nutcracker phenomenon.
A, B. Grayscale ultrasonography (US) (A) and color Doppler US (B) images of the left renal vein (LRV) show the space between the abdominal aorta (AA) (a) and superior mesenteric artery (s) is wide and the LRV is not compressed by the right renal artery origin. The LRV is stretched and thinned (arrows) anterior to the AA (a). Note the jetting flow with color aliasing (arrowheads) from the site where LRV is stretched anterior to the AA into the inferior vena cava. Additionally, the homogeneous color signal in the hilar left renal vein indicates smooth antegrade flow (asterisk).
Other Subtypes of NCP Associated with Congenital Variations of LRV and IVC
Congenital variations of the LRV are associated with NCP, including the retroaortic LRV. In this variation, the LRV travels behind the AA and becomes compressed in the tight space between the AA and the vertebrae. When NCP occurs in a retroaortic LRV, it is termed posterior NCP. Conversely, NCP occurring in the normally positioned LRV, which is situated in front of the AA, is referred to as anterior NCP.
Another variation involves a circumaortic LRV, where the LRV has both anterior and posterior branches encircling the AA. In this case, the preaortic branch follows the normal course ventral to the AA, while the retroaortic branch descends caudally in the lower lumbar region. Typically, the preaortic and retroaortic branches are of equal size. Circumaortic LRV may be associated with anterior NCP, posterior NCP, or a combination of both.
Congenital variations of the IVC, such as a left-sided IVC or double IVC, may also be associated with NCP. In these anomalies, a significant portion of blood from the left lower extremity is channeled through the left-sided IVC and crosses the midline via the LRV, along with the blood from the left kidney. This creates a competition for space between the blood flow from the left kidney and the substantial blood flow from the left lower extremity, forcing it through a functionally narrow area and leading to NCP.
How We Can Help NCS Patients with Doppler US Examinations
Patients with hematuria, proteinuria, and flank pain often experience significantly more anxiety than doctors might realize, especially when the cause remains unidentified despite various tests. Many patients with recurrent unexplained hematuria fear that a cancerous growth in their urinary tract is being overlooked by their doctors. Similarly, even when doctors suggest monitoring mild, persistent proteinuria, many patients still worry that they will eventually develop chronic kidney failure, requiring dialysis or a transplant. In cases where Doppler US reveals NCP, and patients are informed about what it is and how it can be alleviated, their severe anxiety can be greatly reduced, leading to a much more comfortable mental state. Understanding the differences in the severity of NCP depending on sleep position and making changes to sleep habits often lead to symptom improvement. Therefore, Doppler US plays a significant role in these patients, and it is not uncommon for it to result in a marked improvement in their quality of life. In addition to correcting sleeping posture, medication may be prescribed to alleviate the patient’s symptoms. If severe symptoms, such as persistent gross hematuria or intractable flank pain, continue, surgical or interventional options—such as LRV transposition, left gonadal vein transposition, autotransplantation of the left kidney, or internal or external stenting of the LRV—may be considered.
When diagnosing NCS using Doppler US, it is essential to consider a critical point. For instance, if NCP is detected in a patient with hematuria via Doppler US, it might be identified as the cause of the hematuria. However, there could be a more severe underlying issue, such as undetected bladder cancer. It is crucial not to overlook such significant conditions, even in the presence of NCP, to ensure that the primary cause of the symptoms is accurately identified.
Summary
NCS is not uncommon and can present with a variety of typical or atypical symptoms. Doppler US plays a crucial role in the detection of NCP and the management of NCS. It is essential for both examiners and patients to understand the Doppler US findings of NCP in relation to the patient's postural changes.
Notes
No potential conflict of interest relevant to this article was reported.
References
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Notes
Key point
Doppler ultrasonography is a valuable tool for detecting the nutcracker phenomenon and provides crucial dynamic insights for managing patients with nutcracker syndrome.