Percutaneous Nitinol Stent Implantation in the Treatment of Nutcracker Syndrome in Young Adults

Antonio Basile, MD, Dimitrios Tsetis, MD, Giacomo Calcara, MD, Michele Figuera, MD, Maria Teresa Patti, MD, Giovanni Carlo Ettorre, PhD, and Antonio Granata, MD

The present report describes three young adults with nutcracker syndrome caused by left renal vein stenosis managed with nitinol stent implantation. The patients treated included a 20-year-old woman with persistent microhematuria and dyspareunia and two 18-year-old men with proteinuria, hematuria, and flank pain. All three patients were asymptomatic after a follow-up of 14 18 months.
J Vasc Interv Radiol 2007; 18:10421046 Abbreviations: IVC inferior vena cava, LRV left renal vein, SMA superior mesenteric artery

THE clinical syndrome caused by impingement of the left renal vein (LRV) between the superior mesenteric artery (SMA) and abdominal aorta has been termed nutcracker syndrome (1). Although often asymptomatic, entrapment of the LRV is a rare but acknowledged cause of ovarian vein syndrome, varicocele, pelviureteral and peripelvic varices, LRV hypertension, hematuria, orthostatic proteinuria, and unexplained left flank or abdominal pain (2). Surgical approaches for the treatment of nutcracker syndrome include nephrectomy, nephropexy, renocaval reimplantation, and autotransplantation (2).

Published reports of successful treatment of LRV compression in young adults and of the use of nitinol stents have been sparse. Herein we describe successful treatment of LRV compression in three young adults, with follow-up ranging between 14 and 18 months. Institutional review board approval was not needed for this study.

CASE REPORTS
Case 1 A 20-year-old woman was admitted to the nephrology department for clinical assessment after the detection of microscopic hematuria 1 month earlier. She reported left flank pain for the previous 9 months. On questioning, she also reported symptoms of dyspareunia. Findings of physical examination were unremarkable. Urinalysis revealed microscopic hematuria and minimal proteinuria. Renal ultrasonography (US) revealed normalsized kidneys (right, 107 mm; left, 118 mm in length). Repeated US and Doppler flow analysis revealed a patent LRV that abruptly narrowed between the aorta and the SMA. The anteroposterior diameters of the LRV were 12.8 mm in the hilar area and 2.1

From the Department of Diagnostic and Interventional Radiology (A.B., G.C., M.T.P.), Ospedale Ferrarotto; Departments of Radiology (M.F.) and Nephrology (A.G.), Ospedale Vittorio Emanuele; Department of Radiology (G.C.E.), University Hospital of Catania, Catania, Italy; and Department of Radiology (D.T.), University Hospital of Heraklion, Medical School of Crete, Crete, Greece. Received December 7, 2006; final revision received May 11, 2007; accepted May 14, 2007. Address correspondence to A.B., Via Trieste 14, 95127 Catania, Italy; E-mail: antodoc@yahoo.com None of the authors have identified a conflict of interest. SIR, 2007 DOI: 10.1016/j.jvir.2007.05.017

mm in the narrow portion, and the ratio of anteroposterior diameters was 6.10. The peak velocities in the LRV at the hilar and aortomesenteric portions were 19 cm/sec and 87 cm/sec, respectively. After informed consent was obtained, the LRV was catheterized from a right common femoral vein approach. The pressure gradient between the LRV and the inferior vena cava (IVC) at the level between the aorta and the SMA was 6 mm Hg. Venography revealed capsular venous varices joining the left ovarian vein at the lumbar region (Fig 1a), and a 14 40-mm nitinol self-expandable stent (Luminexx; C.R. Bard Angiomed, Karlsruhe, Germany) was then inserted through a 7-F sheath over a stiff wire (0.035-inch Amplatz super-stiff wire; Boston Scientific, Nanterre, France). To prevent the stent from protruding into the IVC, it was inserted under road-mapping guidance with a long sheath at the LRV ostium. Postprocedural venography demonstrated normal flow through the LRV with no pressure gradient between the LRV and the IVC (Fig 1b). To prevent thrombosis, intravenous heparin was administered for 2 days and was followed by oral aspirin therapy. The patient experienced flank pain for 3 days after the intervention,

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Figure 1. (a) Phlebography of the LRV demonstrates the capsular varices supplying the left ovarian vein. (b) Control image after stent placement shows direct flow toward the IVC; capsular varices are no longer detected.

and analgesic therapy was given during this period. At 18-month followup, the patient was asymptomatic with normal Doppler US findings. Case 2 A well developed 18-year-old man was admitted to the nephrology department for clinical assessment after the detection of proteinuria with left flank pain. He was normotensive and the findings of physical examination were normal. Urinalysis was normal except for 3 proteinuria and 24-hour urinary protein excretion of 0.9 1.2 g. His nighttime urine was protein-free, but while he was in an upright and ambulatory position in the daytime, urine specimens contained protein. A very high -globulin peak was detected by urinary protein electrophoresis. Serum creatinine, blood urea nitrogen, total protein, and albumin levels were within normal limits, as was creatinine clearance. US examination showed anomalous position and dilation of the LRV: anteroposterior diameters of the LRV were 13.5 mm in the hilar area and 1.7 mm in the narrow portion and the ratio of anteroposterior diameters was 7.9. Doppler US peak velocity measurements in the LRV were 23 cm/sec in the hilar area

and 107 cm/sec in the narrow portion, for a ratio of 4.65. Enhanced computed tomography (CT) imaging demonstrated stenosis of the LRV between the aorta and SMA; in addition, a ventral ectopic origin of the right renal artery increased the stenosis just at the renocaval junction with dilated lumbar varices. After informed consent was obtained, phlebography was performed to confirm and allow treatment of the stenosis. From a right common femoral vein approach, the LRV was catheterized. The pressure gradient between the LRV and the IVC was 7 mm Hg with the presence of lumbar varices; two 14 40-mm self-expandable nitinol stents (Luminexx; C.R. Bard Angiomed) were inserted through a 7-F sheath over a stiff wire (0.035-inch Amplatz super-stiff wire; Boston Scientific). To prevent the stent from protruding into the IVC, it was inserted under road-mapping guidance with a long sheath at the LRV ostium. Postprocedural venography demonstrated no retrograde flow toward the lumbar veins, with disappearance of the renocaval pressure gradient. To prevent thrombosis, intravenous heparin was administered for 2 days and was followed by oral aspirin therapy. At 15-

month follow-up, the patient was asymptomatic. Case 3 An 18-year-old man was admitted to the nephrology department with a 10-month history of intermittent gross hematuria. There was no renal disease in the patients history. He had undergone percutaneous embolization for a varicocele 8 months earlier, but there was a recurrence 1 month later. Blood chemistry findings were normal. Urinalysis revealed hematuria and minimal proteinuria. US imaging of kidneys was normal. Cystoscopy showed light bleeding from the left ureter. Repeated US and Doppler flow analysis revealed a patent LRV that abruptly narrowed between the aorta and the SMA. Doppler study showed that the diameter of the hilar and aortomesenteric portions of the LRV were 13.6 mm and 2.2 mm respectively, for a ratio of 6.1. The peak velocities in the LRV at the hilar and aortomesenteric portions were 9 cm/sec and 78 cm/ sec, respectively, for a ratio of 8.6. Enhanced CT imaging demonstrated stenosis of the LRV between the aorta and SMA (Fig 2a). After informed consent was obtained, the LRV was catheterized from a right common femoral

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Figure 2. (a) Multidetector CT image reveals the LRV stenosis between the aorta and the SMA. (b) Phlebography of the LRV demonstrates capsular varices. (c) Control image after stent placement shows direct flow toward the IVC.

vein approach. The pressure gradient between the LRV and the IVC at the level between the aorta and the SMA was 7 mm Hg. Venography revealed capsular varices (Fig 2b). A 14 40-mm self-expandable nitinol stent (Luminexx; C.R. Bard Angiomed) was inserted through a 7-F sheath over a stiff wire (0.035-inch Amplatz superstiff wire; Boston Scientific). To prevent the stent from protruding into IVC, it was inserted under road-mapping guidance with a long sheath at the LRV ostium. Postprocedural venography demonstrated normal flow through the renal vein with no pressure gradient between the LRV

and IVC (Fig 2c). To prevent thrombosis, intravenous heparin was administered for 2 days and was followed by oral aspirin therapy. The patient experienced flank pain for 24 hours after the intervention, and analgesic therapy was given during this period. After 14 months of follow-up, the patient was asymptomatic with normal findings on Doppler US flow analysis.

DISCUSSION
The nutcracker syndrome is caused by LRV compression between the SMA and aorta, leading to retrograde endovenous hypertension (3). Two peaks

of incidence at young and middle age have been reported, which likely correspond to two different stages of the disease (2). At an early stage, the LRV compression leads to LRV hypertension compensated by development of venous collateral vessels (usually renal capsular veins), which increases venous capacitance. Because of the competence of the venous valve of the ovarian or lumbar vein, no direct or low reflux is seen in these vessels at this stage. LRV hypertension leads to the development of direct communication between the dilated venous sinuses and adjacent calyces with related essential hematuria and flank pain (4 6).

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Published Cases of Endovascular Stent Implantation for Nutcracker Syndrome Study, Year Neste et al (20), 1996 Segawa et al (21), 1999 Park et al (22), 2000 Scultetus et al (7), 2001 Chiesa et al (23), 2001 Wei et al (24), 2003 Lin et al (25), 2003 van der Laan et al (26), 2004 Kim et al (27), 2005 Hartung et al (28), 2005 No. of Pts. 1 1 1 1 1 Sex/Age (y) NS F/40 M/47 F/40 M/17 Symptoms NS Asymptomatic gross hematuria Hematuria PCS Flank pain, hematuria Stent NS 70 20-mm covered stent 18-mm nitinol stent 60-mm Palmaz stent 16 30-mm Wallstent and 20 40-mm nitinol stent Wallstent 12 40-mm Wallstent NS 10 65-mm Wallstent 20-mm/60-mm (n 1); 16-mm/60-mm (n 2); 40-mm/ 16-mm (n 2) Follow-up (months) NS 6 4 24 12

1 3 1 1 5

M/37 M/22.7 F/36 F/47

18.0

Gross hematuria Gross hematuria, left flank pain Flank pain Gross hematuria Long-standing incapacitating PCS (n 2); left lumbar pain (n 2); microscopic hematuria (n 2); left limb atypical varices with venous insufficiency symptoms (n 1) Gross hematuria

3 50 (mean, 24.7 15 24

18.0)

F/34.7 (mean)

4.226.5 (mean, 14.3)

Chen et al (29), 2005

M/10 (mean)

10 40-mm selfexpandable nitinol stent

2436

Note.NS

not specified; PCS

pelvic congestion syndrome.

At a later stage, the persistence of chronic LRV hypertension causes valvular incompetence and massive reflux of blood into ovarian or lumbar veins, leading to pelvic or vulvar varices with the classical symptomatology of pelvic congestion syndrome (ie, pelvic pain, dyspareunia, dysuria, or dysmenorrhea). This is mainly encountered in middle-aged women (6,7). Diagnostic imaging may involve Doppler US, CT, or magnetic resonance (MR) imaging examinations, but phlebography with renal vein and IVC manometry is definitive, particularly a renocaval pressure gradientmeasured as the pressure in the LRV minus the pressure in the IVC of more than 3 mm Hg (8,9). US findings suggesting nutcracker syndrome are related to proximal-to-aortomesenteric LRV diameter ratios and aortomesenteric-to-proximal LRV peak velocity ratios. Kim et al (10) identified Doppler US criteria related to the nutcracker phenomenon by measuring LRV diameter and peak flow velocity. The authors suggested that distal-to-prox-

imal diameter ratios and flow velocity ratios exceeding 5.0 represented cutoff levels for the diagnosis of nutcracker phenomenon; in addition, Kim and colleagues (11) recently reported the first study of the correlation between Doppler parameters of the LRV and the renocaval pressure gradient in pediatric patients with varicocele and concluded that the nutcracker phenomenon may be an important cause of pediatric varicocele. The authors stated that LRV hypertension provides the driving force for retrograde blood flow into the internal spermatic vein and that it is correlated with Doppler spectral analysis (11). MR imaging and helical CT have been recently used in the diagnosis of this phenomenon, and these tools are also able to distinguish anterior nutcracker phenomena (ie, LRV stenosis between aortomesenteric angle) and posterior nutcracker phenomena (ie, retroaortic LRV compressed between the aorta and spine) (1215). The therapy for nutcracker syndrome is still controversial. For asymp-

tomatic hematuria and orthostatic albuminuria, follow-up or conservative treatment with hemostatic agents (eg, carbazochrome) have been suggested. For more symptomatic conditions, including severe hematuria with related anemia, back pain, or renal function impairment unresponsive to conservative therapy after 24-month follow-up, more aggressive management is suggested (8). Surgical procedures including medial nephropexy (6), renal vein bypass (16), transposition of the LRV (17), transposition of the SMA (18), gonadocaval bypass in patients with nutcracker syndrome associated with pelvic varices (7), and autotransplantation of the left kidney (19) have been reported to alleviate LRV compression, with varying results and complication rates. Recently, after the first case of LRV stent implantation reported by Neste et al in 1996 (20), 19 cases of interventional radiologic management of nutcracker syndrome have been reported with follow-up periods ranging from 3 to 54 months (7,20 29) (Table).

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Various types and sizes of stents have been used, ranging in diameter from 10 to 20 mm. Rare reported complications of these procedures are stent fracture, migration, thrombosis, and in-stent restenosis. Particularly because of their flexibility and resistance to external force, nitinol stents may be indicated in the treatment of stenosis of an LRV compressed between two large pulsatile arteries. Their use in nutcracker syndrome could also improve the effectiveness of endovascular therapy in such cases. In the literature published to date, the ages of treated patients have ranged from 17 to 47 years, which perfectly matches the two peaks of incidence of symptomatology previously described. Recently, a study reporting the treatment of three consecutive male pediatric patients with nutcracker syndrome has been published (29). This article suggested that stent implantation may be indicated even in pediatric patients, but we and others (30) believe the preferred therapy for hematuria in childhood nutcracker syndrome is observation, as aortomesenteric compression may resolve spontaneously as a result of physical development during childhood, and there may be possible problems related to the rigidity of the stent during normal body development (31). In addition, we have additional concerns regarding possible complications related to the rigidity of a stent in the setting of normal development of the body. For this reason, we would offer endovascular stent implantation in such patients only when body development is finished, as was the case in the patients described herein. Although longer follow-up in more patients is still needed to assess the role of stent implantation in the management of nutcracker syndrome, percutaneous treatment with nitinol stents in young adults seems to be effective and safe in the short term.
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