700Case Report

Nutcracker syndrome, which was first describedby De Schepper, refers to compression of the

left renal vein between the aorta and superior mesen-teric artery.(1) The compression impairs blood flowthrough the left renal vein, and creates a highervenous pressure gradient, leading to congestion ofthe left kidney and occasionally formation of collat-eral circulation. It is an unusual cause of hema-turia.(1-8) Because routine diagnostic tools are of littlehelp in making a diagnosis, patients with this diseasecharacteristically undergo repeated diagnostic proce-dures and blood transfusions, and treatment is usual-ly delayed.(2,8)

CASE REPORT

A 25-year-old woman was admitted to our hos-pital with intermittent gross hematuria and intermit-tent left flank pain in December 1994. There was nohistory of upper respiratory infection prior toepisodes of hematuria before the first admission.Her medical history was otherwise unremarkable.She weighed 43 kg and was 156 cm tall. Her bloodpressure was 110/70 mmHg, pulse rate 80/min, res-piratory rate 16/min, and body temperature 36.5 oC.Her physical examination was normal. There was notenderness at the costovertebral angle or lower legedema. At that time, urinalysis showed numerous

Nutcracker Syndrome: An Overlooked Cause of Hematuria

Yu-Ming Chen, MD, PhD; I-Kuan Wang1, MD; Koon-Kwan Ng', MD and Chiu-Ching Huang, MD.

Nutcracker syndrome is caused by compression of the left renal vein between the aortaand the superior mesenteric artery, where it courses in the fork formed at the bifurcation ofthese arteries. The phenomenon results in left renal venous hypertension, which leads to leftrenal vein and left gonadal vein varices and unilateral hematuria. The main presentingsymptom is hematuria, with or without left flank pain. The disorder is easily missed by rou-tine diagnostic methods. Its incidence is likely underestimated. We report on a 25-year-oldwoman who experienced intermittent gross hematuria and left flank pain. The diagnosis ofnutcracker syndrome was missed initially. Abdominal computed tomography, angiography,venography, and magnetic resonance angiography, which were later performed, showed thatthe left renal vein was compressed between the aorta and the superior mesenteric artery.The pressure gradient between the left renal vein and the inferior vena cava was 6.8 cm H2O.A diagnosis of nutcracker syndrome was established. She refused surgery and was lost tofollow-up. The diagnosis and treatment of nutcracker syndrome are discussed. Magneticresonance angiography is a safe and reliable tool for diagnosing this disorder. (Chang GungMed J 2002;25:700-5)

Key words: nutcracker syndrome, left renal venous hypertension, hematuria.

From the Department of Nephrology, 1Department of Radiology, Chang Gung Memorial Hospital, Taipei; School of Medicine,Chang Gung University, Taoyuan.Received: Oct. 3, 2001; Accepted: Jan. 2, 2002Address for reprints: Dr. I-Kuan Wang, Department of Nephrology, Chang Gung Memorial Hospital. 6, Section West, Chai PuRoad, Pu Tz, Chai Yi 613, Taiwan, Tel.: 886-5-3621000; Fax: 886-5-3621000; E,-mail: Ikwang@seed.net.tw

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red blood cells, protein of 100 mg/dl, and 3-5 whiteblood cells per high-power field. Blood chemistrytests showed BUN of 16 mg/dl and creatinine of 0.7mg/dl. Hemoglobin was 12.0 gm/dl, and the whiteblood cell count was 7900/mm3. Antinuclear anti-body was negative; C3 was 105 mg/dl (normal71.87-122.03); and C4 was 13.5 mg/dl (normal 9.92-29.96 mg/dl). IgA was 174 mg (normal 71.20-434.12 mg/dl); IgG was 1570 mg/dl (normal 835-1716 mg/dl); and IgM was 265 mg/dl (normal 24.29-198.69 mg/dl). Prothrombin time, partial thrombo-plastin time, and bleeding time were normal. Urinecytology and cultures for tuberculosis bacilli werenegative. Renal ultrasonography showed normalrenal size and outline with no anatomical defect.The length of the left kidney was 10.6 cm, and thatof the right was 10.9 cm. The result of intravenouspyelography was normal. Cystoscopy showed bleed-ing from the bilateral ureteral orifices. Retrogradepyelography revealed filling defects in the left renalpelvis and upper ureter, which were possibly causedby blood clots. On light microscopy, the histology ofthe renal biopsy was normal. Immunofluorescenceshowed trace depositions of IgA, IgM, and C1q inthe mesangial areas. Hence, IgA nephropathy wassuspected. The patient was discharged without med-ication. However, intermittent gross hematuria per-sisted and some episodes were preceded by upperrespiratory tract infection. So, she was again admit-ted in September 1998. Renal ultrasonographyshowed dilatation of the left renal vein in the hilar

Fig. 1 CT scan showing dilatation of the distal left renal vein(LRV) with narrowing between the superior mesenteric artery(SMA) and the aorta (Ao) (arrow).

A

B

123

123

Fig. 2 (A) (B) Simultaneous angiography and venographyshowing narrowing of the proximal left renal vein (1) withfilling defects due to compression by the superior mesentericartery (2) and aorta (3). (C) Venography showing reflux of theleft renal venous flow into the left ovarian vein (arrow).

C

vein was compressed between the aorta and the supe-rior mesenteric artery (Fig. 1). Angiography andvenography also showed filling defects in the leftrenal vein because of compression by the aorta andthe left renal vein (Fig. 2A, B). In addition, therewere prominent periureteral and peripelvic venouscollaterals and reversal of the left renal venous bloodflow into the left ovarian vein (Fig. 2C). The pres-sure gradient between the left renal vein and inferiorvena cava was 6.8 cm H2O. Magnetic resonanceangiography (MRA) showed compression of the leftmid-renal vein between the superior mesentericartery and the aorta. The distal third of the left renalvein was dilated, whereas the proximal third was rel-atively small in caliber (Fig. 3A, B). Cystoscopywas again performed, and it showed bleeding fromthe left ureteral orifice. Therefore, nutcracker syn-drome was our impression. Surgery was suggested.However, the patient refused, and was lost to follow-up thereafter.

DISCUSSION

Compression of the left renal vein was firstdescribed in 1950.(9) In 1972, De Schepperdescribed compression of the left renal vein betweenthe aorta and the superior mesenteric artery as nut-cracker syndrome.(1) Nutcracker syndrome occursmost frequently in young women. It has been associ-ated with unilateral hematuria, gonadal vein syn-drome, and varicocele.(3,10) Various degrees of pro-teinuria are present.(11) Unilateral hematuria is due toabnormal communication between the submucosalvenous plexus and the calyceal system presumablyinduced by renal venous hypertension.(3) Thegonadal vein syndrome is characterized by abdomi-nal and flank pain exacerbated by sitting, standing,or walking.(2) Zerhouni et al. reported the nutcrackerphenomenon in 3 patients investigated for varico-cele.(10)

The pathophysiology of nutcracker syndrome isnot well known. It was proposed that posterior renalptosis with stretching of the left renal vein may be afactor.(4) In recent studies, abnormal branching of thesuperior mesenteric artery from the aorta was identi-fied as its cause.(8,12)

Nutcracker syndrome cannot be diagnosed withroutine diagnostic methods. Therefore, it is easilymisdiagnosed or undiagnosed. Intravenous pyelog-

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area. The length of the left kidney was 11.3 cm andthat of the right 10.3 cm. Blood biochemistry andcomplete blood count were normal. AntistreptolysinO antibody was 155 IU/ml (normal < 200 IU/ml),and IgA was 187.0 mg/dl. Abdominal computedtomography (CT) scan revealed that the left renal

A

B

Fig. 3 (A) MRA showing the left renal vein (1) being com-pressed by the superior mesenteric artery (2) and the aorta (3).(B) An oblique view of MRA showing the steep anglebetween the superior mesenteric artery and the aorta.

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raphy may show notching by varicosities, cystoscopymay reveal bleeding from the left ureteral orifice,and a CT scan may show compression of the leftrenal vein between the aorta and superior mesentericartery and the coexistence of abnormal venous collat-erals.(6) Angiographic CT, magnetic resonance imag-ing (MRI), and MRA can also be used as diagnostictools.(8,12,13) In this case, we demonstrated the findingson angiography, CT, and MRA. MRA is less inva-sive than angiography and can be used initially fordetecting this rare cause of hematuria.Ultrasonography and Doppler ultrasonography arealternative noninvasive methods for diagnosis.(11,14)

Kim et al. reported that the ratio of the diameter ofthe left renal vein between the hilar portion and theaortomesenteric portion is greater than 5 in patientswith nutcracker syndrome. In addition, the ratio ofthe peak velocity of the left renal vein between theaortomesenteric portion and the hilar portion is alsogreater than 5 in patients with this syndrome.(11)

Takebayashi et al. reported that the sensitivity andspecificity of color Doppler sonography for diagnos-ing the nutcracker syndrome were 78% and 100%,respectively.(14) Venography combined with venouspressure measurement is recognized as the procedureof choice for diagnosis.(6,7) Venography may shownarrowing of the renal vein where it crosses the aortabeneath the superior mesenteric artery, dilatation ofthe distal left renal vein, and opacification of tribu-taries of the left renal vein (the gonadal, ascendinglumbar, adrenal, ureteral, and capsular veins). Thepressure gradient may range from 4.9 to 14.0 cmH2O in patients with nutcracker syndrome, whereasnormal values range from 1.3 to 10 cm H2O.(4,6,8,15) Inour patient, the pressure gradient between the leftrenal vein and inferior vena cava was 6.8 cm H2O.

In our patient, immunofluorescence on renalbiopsy showed trace depositions of IgA, IgM, andC1q in the mesangial areas, and the result of the firstcystoscopy showed bleeding from the bilateralureteral orifices. Therefore, the possibility of nut-cracker syndrome combined with IgA nephropathycannot be excluded. Ozono et al. reported 2 patientswith nutcracker syndrome associated with IgAnephropathy.(16)

Conservative treatment has been suggested formild hematuria.(7) Surgery is indicated for severepersistent or recurrent gross hematuria causing ane-mia and bothersome abdominal or flank pain.(5,8)

Medial nephropexy with excision of the renal vari-cosities, left renal vein bypass, and transposition ofthe left renal vein have been described.(2,4,5,8)

Autotransplantation is an alternative treatment thatprovides the kidney with better protection fromischemia.(17) An intravascular stent, which can beplaced with minimal invasiveness, offered physio-logical relief in a recently reported case.(18)

In conclusion, nutcracker syndrome is a rarecause of hematuria and is easily missed by routinediagnostic methods. Hence, patients with unknowncauses of unilateral hematuria and flank pain shouldundergo further studies such as ultrasonography, CT,MRI, MRA, angiography, or venography to clarifythis possibility. MRA is a safe and reliable tool fordiagnosing this disorder.

REFERENCES

1. De Schepper A. "Nutcracker" phenomenon of the renalvein causing left renal pathology. J Belg Rad 1972;55:507-11.

2. Coolsaet BLRA. Ureteric pathology in relation to rightand left gonadal veins. Urology 1978;12:40-9.

3. Lopatkin AN, Morozov AV, Lopatkin LN. Essential renalhemorrage. Eur Urol 1978;4:115-8.

4. Wendel RG, Crawford ED, Hehman KN. The nutcrackerphenomenon: an unusual cause for renal varicosities withhematuria. J Urol 1980;123:761-3.

5. Stewart BH, Reiman G. Left renal venous hypertension'nutcracker' syndrome managed by direct renocaval reim-plantation. Urology 1982;20:365-9.

6. Weiner SN, Bernstein RG, Morehouse H, Golden RA.Hematuria secondary to left peripelvic and gonadal veinvarices. Urology 1983;22:81-4.

7. Dever DP, Ginsburg ME, Millet DJ, Feinstein MJ,Cockett ATK. Nutcracker phenomenon. Urology 1986;27:540-2.

8. Hohenfellner M, Steinbach F, Schultz-Lampel D,Schantzen W, Walter K, Cramer BM, Thuroff JW,Hohenfellner R. The nutcracker syndrome: new aspects ofpathophysiology, diagnosis and treatment. J Urol1991;146:685-8.

9. El Sadr AR, Mina A. Anatomical and surgical aspects inthe operative management of varicoceles. Urol Cut Rev1950;54:257-62.

10. Zerhouni EA, Siegelman SS, Walsh PC, White RI.Elevated pressure in the left renal vein in patients withvaricocele: preliminary observation. J Urol 1980;123:512-3.

11. Kim SH, Cho SW, Kim HD, Chung JW, Park JH, HanMC. Nutcracker syndrome: diagnosis with Doppler US.Radiology 1996;198:93-7.

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12. Shokeir AA, EL-Diasty TA, Ghoneim MA. The nutcrack-er syndrome: new methods of diagnosis and treatment. BrJ Urol 1994;74:139-43.

13. Takemura T, Iwasa H, Yamamoto S, Hino S, FukushimaK, Isokawa S, Okada M, Yoshioka K. Clinical and radio-logical features in four adolescents with nutcracker syn-drome. Pediatr Nephrol 2000;14:1002-5.

14. Takebayashi S, Ueki T, Ikeda N, Fujikawa A. Diagnosisof the nutcracker syndrome with color Doppler sonogra-phy: correlation with flow patterns on retrograde left renalvenography. AJR Am J Roentgenol 1999;172:39-43.

15. Beinart C, Sniderman KW, Tamura S, Vaughan ED Jr, SosTA. Left renal vein to inferior vena cava pressure relation-ship in humans. J Urol 1982;127:1070-1.

16. Ozono Y, Harada T, Namie S, Ichinose H, Shimamine R,Nishimawa Y, Hara K. The nutcracker phenomenon withIgA nephropathy. J Intern Med Res 1995;23:126-31.

17. Chuang CK, Chu SH, Lai PC. The nutcracker syndromemanaged by autotransplantation: J Urol 1997;157:1833-4.

18. Park YB, Lim SH, Ahn JH, Kang E, Myung SC, Shim HJ,Yu SH. Nutcracker syndrome: intravascular stentingapproach. Nephrol Dial Transplant 2000;15:99-101.

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