Diagnosis of nut-cracker phenomenon using renal Doppler ultrasound in orthostatic proteinuria
Byoung-Soo Cho1,,
Young-Mi Choi1,
Hyeon-Ho Kang1,
Seong Jin Park2,
Joo Won Lim2 and
Tai Young Yoon3
Department of 1Pediatrics,
2 Radiology, and
3 Preventive Medicine, College of Medicine, Kyung Hee University, Seoul, Korea
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Abstract
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Background. We evaluated the efficacy of non-invasive renal Doppler ultrasound (US) to detect the nut-cracker phenomenon (NCP) and we studied the prevalence of NCP in children with orthostatic proteinuria.
Methods. Among a total 66 cases of orthostatic proteinuria, 39 cases of NCP were found, with 27 cases being detected in a normal control group. Using Doppler US, the anteroposterior (AP) diameter and peak velocity (PV) of the left renal vein (LRV) were measured at the hilar and aortomesenteric portion. We calculated the ratio of AP and PV diameters between the two portions. The parameters were analysed using Student's t-test.
Results. The AP diameters and the ratio in the hilar and narrow portions were all significantly different between the two groups (P<0.01). The PV in the narrow portion and the ratio of PV were significantly different (P<0.01), but the PV in the hilar portion was not statistically different between the two groups (P>0.05). If the diagnostic criteria for NCP was that the ratio of PV was more than 5, then 22 subjects (56.4%) in the orthostatic proteinuria group and none in the control group could be diagnosed as NCP. If, however, the cut-off values for the diagnosis of NCP were set at the mean±2 SD of the ratio (PV ratio 3.98 and size ratio 4.16), then the orthostatic proteinuria group showed abnormal AP diameter in 25 (64.1%), peak velocity in 28 (71.8%), and both in 21 patients (53.8%), and the control group showed an abnormal AP diameter in one subject (3.7%).
Conclusions. NCP may be one of the leading causes of orthostatic proteinuria, and non-invasive renal Doppler US may be a useful diagnostic tool in the screening of NCP. In the future, the diagnostic criteria of NCP must be redefined in children.
Keywords: nut-cracker phenomenon; orthostatic proteinuria; renal Doppler ultrasound
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Introduction
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Compression of the left renal vein (LRV) between aorta and superior mesenteric artery (SMA), resulting haematuria, flank pain, varicocele, etc. is termed nut-cracker phenomenon (NCP) or left renal vein entrapment syndrome. In the past invasive venography has been used for the diagnosis of NCP, but recently non-invasive methods such as computed tomography (CT), ultrasound (US), and magnetic resonance imaging (MRI), etc. have been used more frequently. Most of the studies were performed in cases of haematuria. As yet, no large studies have been reported in orthostatic proteinuria. The purpose of this study is to assess the utility of renal Doppler US for the diagnosis of NCP in children. We also investigated the prevalence of NCP among patients with orthostatic proteinuria.
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Subjects and methods
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Subjects
From the years 1997 to 1999 we evaluated 39 cases of NCP in an orthostatic proteinuria group, who were followed for at least 3 months, and who manifested normal BUN, creatinine, and blood pressure. Also, a normal control group (28 cases) with no evidence of renal disease or other chronic diseases were selected. We diagnosed subjects as having orthostatic proteinuria by the following criteria: no proteinuria in the early morning urine by dipstick test, more than 2+ proteinuria by dipstick test in the daytime urine, and less than 1 g of proteinuria in 24-h collected urine.
In the orthostatic proteinuria group, male : female ratio was 1.1 : 1 and mean age was 11 (616) years. No subjects had haematuria by dipstick test. In the control group, male : female ratio was 0.9 : 1 and mean age was 10 (616) years. There were no statistically significant differences between the groups.
Methods
After having fasted for 68 h, the patients ingested 150300 ml tap-water 1530 min before the US examination; US was then carried out using HDI 3000 with 74 and 42 MHz convex transducers and with the subjects supine. In the early part of this study we tried to obtain data in two positions, supine and upright. However, we could not obtain sonographic data in the upright position, because bowel gas interfered with sonographic examination of the left renal vein. Therefore, we obtained sonographic data only in the supine position. We calculated the mean of each parameter in each patient. We measured each parameter three times. Anteroposterior (AP) diameter and peak velocity (PV) were measured three times at two points in the LRV, one at the lateral portion of the LRV near the hilum, and the other as the LRV courses between the aorta and the SMA (aortomesenteric portion). PV was measured in the transverse and longitudinal planes. The diameter of the LRV was measured with callipers at two points on grey-scale US, and the Doppler angle was kept at less than 60° (Figures 1
and 2
). All of the US examinations and interpretations of images were performed by two radiologists using the same methods. We obtained sonographic data in a blinded manner, not knowing whether the subjects had orthostatic proteinuria or were normal control subjects.

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Fig. 1. Using Doppler US, peak velocity of the left renal vein in the hilar portion measured 19.9 cm/s.
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Fig. 2. The velocity of the left renal vein in the narrow portion was 116.3 cm/s; it was six times faster in the hilar portion.
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Statistics
We calculated the absolute values of the LRV as well as the ratio of PV and AP diameter between the two measured points, and compared the orthostatic proteinuria group with the control group. We performed statistical analysis with Student's t-test, using SPSS, and analysed correlations between the ratio of PV and AP diameter of the LRV in the orthostatic proteinuria group with Pearson's correlation coefficient. The mean ± 2 SD of ratio of AP diameter and PV of the LRV between aortomesenteric and hilar portions was calculated for normal controls, and was used as the cut-off value for diagnosing NCP. We also analysed the proportion of NCP in the orthostatic proteinuria group.
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Results
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The mean AP diameter of the LRV in the orthostatic proteinuria group was 7.60 mm in the hilar area, 1.66 mm in the narrow portion, and the mean ratio of AP diameter was 5.50. In contrast, the mean diameter of the LRV in the normal control group was 6.13 mm in the hilar area, 2.35 mm in the narrow portion, and the mean ratio of AP diameter was 2.77 mm. Between the two groups, the AP diameter in the hilar and narrow portions and the ratio of diameter were all significantly different (P<0.01) (Table 1
, Figure 3
).
The results of peak velocity of LRV were that the mean PV of the orthostatic proteinuria group was 19.88 cm/s in the hilar area and 101.67 cm/s in the narrow portion, and the mean ratio of PV was 5.52. In the normal control group, the results were 18.04 cm/s, 45.41 cm/s, and 2.57 respectively. The PV in the narrow portion and the ratio of PV were significantly different between the two groups (P<0.01), but the PV in the hilar portion were not statistically different (P>0.05) (Table 2
, Figure 4
).
According to some authors, if the diagnostic criteria for NCP was that the peak velocity ratio is more than 5 [4], 22 cases (56.4%) in the orthostatic proteinuria group and no cases in control group would have been diagnosed as NCP. However, if the cut-off value for the diagnosis of NCP were set at the mean±2 SD (PV ratio 3.98, size ratio 4.16 ), the orthostatic proteinuria group showed an abnormal AP diameter in 25 (64.1%), PV in 28 (71.8%), and both in 21 patients (53.8%), and the control group showed an abnormal AP diameter in one subject (3.7%) (Table 3
).
We analysed the orthostatic proteinuria group with Pearson's correlation coefficient and there were significant correlations between the ratio of the PV and the AP diameter (r=0.776, P=0.000) (Figure 5
).
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Discussion
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The prevalence of asymptomatic proteinuria differs greatly between reports, and findings of 0.6 10.7% [1,2] have been published. Asymptomatic proteinuria may result in renal dysfunction if underlying disease is present and must be followed up carefully. However, half of all cases of asymptomatic proteinuria is due to orthostatic proteinuria, which is a benign condition, and no treatment is necessary because it does not progress to renal failure.
The mechanism of orthostatic proteinuria is not yet clearly defined. Shintaku et al. [3] proposed a partial obstruction to the flow in the LRV. Vehaskari [4] suggested that a mechanism consisting of both an underlying subclinical immune injury and a superimposed exaggerated haemodynamic response would resolve many of the discrepancies. Under this hypothesis, the subtle glomerular injury would not by itself cause protein excretion, or at most would increase it only minimally, and the additional haemodynamic stress of elevated glomerular intracapillary pressure (mediated by angiotensin II) in the upright posture would be required to produce frank proteinuria [4]. Other hypotheses focus on a renal congestion theory. Kelling [5] proposed that the erect posture could close the angle between the aorta and SMA, leading to compression of the LRV and renal congestion. Buchanec et al. [6] observed that renal ptosis was more common in children with orthostatic proteinuria, and emphasized that angling of the renal vein would bring about passive renal congestion. This renal congestion theory of orthostatic proteinuria is very similar to the mechanism of NCP [3,7].
NCP was first described in 1972 by De Schepper [8], and results from compression of the LRV between the aorta and the SMA. The phenomenon is manifested by gross haematuria or microscopic haematuria, left flank pain, varicocele, gonadal vein engorgement, etc. The haematuria may result from increased LRV pressure causing minute rupture of thin-walled veins into the collecting systems or calyceal fornix [9] or communication between dilated venous sinuses and adjacent renal calyces [10]. NCP is a benign condition and if the symptoms are mild, no treatment is necessary. If clinical symptoms are severe, operative treatment such as medial nephropexy with excision of renal varicosities [11], renal-vein bypass [12], autotransplantation [13], etc. should be considered. The mechanism of NCP is unknown. NCP is generally more severe in the erect posture than in the supine position, owing to visceral ptosis or pressure gradients. It is not clear why compression of the vein occurs in some patients.
Shintaku et al. [3] reported that 15 patients with orthostatic proteinuria had entrapment of the LRV by the aorta and SMA, and the NCP may possibly be a cause of moderate to massive orthostatic proteinuria. Lee et al. [7] also reported two NCP patients with orthostatic proteinuria. We were interested in this point and investigated the prevalence of NCP among the orthostatic proteinuria group. Our data showed a definite difference in results between the orthostatic proteinuria group and the normal control group. We supposed that by renal congestion, orthostatic proteinuria and NCP can develop in the same patient, and NCP may cause orthostatic proteinuria.
But our study has some limitations, because we did not examine renal venography, and renal Doppler could not confirm our diagnosis. In addition, because the number of cases was so small, we could not ignore statistical errors.
For the diagnosis of NCP, several diagnostic tools are applied, but definite diagnostic criteria have not yet been established. The widely used diagnostic method of NCP is renal venography. Ekim et al. [14] report a rarer pattern of this phenomenon, so-called posterior nutcracker, as the cause of orthostatic proteinuria. They performed a selective venography and aortography and confirmed the presence of a markedly compressed LRV between the aorta and the luminal vertebral body proximal to the insertion into the inferior vena cava. The cut-off value of differences of pressure between aortomesenteric and hilar portions is proposed as more than 3 mmHg [2,15,16]. However, these criteria have sometimes led to a misdiagnosis of NCP because some children normally have a narrow LRV.
Some have tried non-invasive rather than invasive screening methods (angiographic CT [17], MRI [18], Doppler US [1921], etc). Doppler sonography can provide physiological information about blood flow in the LRV. Kim et al. [20] reported that the measurement of diameter and peak flow velocity in both distal and proximal portions of the LRV is useful for diagnosis of NCP. According to their study, a ratio of AP diameter and PV greater than 5.0 should be the cut-off level for the syndrome. Applying this criterion, sensitivity was 80%, specificity 94%, and accuracy 83% [20], but there was controversy in regard to the criteria. We agree that there are some problems using US for the diagnosis of NCP, but Doppler US is a simple and non-invasive method. For example, measurement of the diameter and the PV of the LRV can vary between operators, and sometimes the image is difficult to obtain because of intestinal gas. Moreover, it is difficult to measure the narrow portion of the PV in children because the sampling area of the LRV is too small and the Doppler angle is larger than in adults, due to the almost horizontal left renal venous flow into the inferior vena cava after the narrow portion. Therefore, very few data have been reported in children and the criteria of childhood NCP has not been established. If the flow velocity can be calculated in the narrow portion of the LRV in children, the Doppler sonographic instrument will become a powerful tool for the diagnosis of NCP.
In our study, it was not difficult to obtain a Doppler spectrum sampling from the left renal vein. Although our number of cases was small, we could obtain Doppler US data in nearly all cases. Our data showed that values are significantly different between the two groups, except for PV in the hilar portion of the LRV. If the criteria for the diagnosis of NCP is a PV ratio of more than 5, and/or the ratio of AP diameter is more than 5, there would be 5356% cases of NCP in our orthostatic proteinuria group, but none in our normal control group. These significant differences are indirect proof that orthostatic proteinuria may be caused by renal congestion resulting from compression of the LRV and that NCP may be one of the common causes of orthostatic proteinuria, because the US finding in our orthostatic proteinuria group fit into the criteria for the diagnosis of NCP.
There are some questions as to why the combined haematuria and proteinuria conditions are not more frequent, and why isolated symptoms are more frequently observed. In addition, there is confusion about the criteria of NCP when using Doppler US. The mean ± 2 SD of ratio may be different between children and adults. Therefore, we think that a larger number of cases must be studied and the mean±2 SD data should be obtained. The criteria of the ratio of AP diameter and PV of more than 5 has been preferred until now. If the data is obtained, it can be used as the criteria for NCP, and Doppler US will become a powerful diagnostic tool in the diagnosis of NCP.
In conclusion, NCP might be one of the leading causes of orthostatic proteinuria, and non-invasive renal Doppler US may be a useful diagnostic tool in the screening of NCP. The diagnostic criteria of NCP in children by Doppler US should be redefined.
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Acknowledgments
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The authors would like to thank Mrs A. Alice for her secretarial support and proof-reading. An abstract of this article was presented at the poster section of 34th ESPN in Helsinki, Finland.
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Notes
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Correspondence and offprint requests to: Byoung-Soo Cho MD PhD, Department of Pediatrics, College of Medicine, Kyung-Hee University Hospital, #1 Hoegi-dong Dongdaemun-ku, Seoul, Korea. 
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Received for publication: 23. 9.00
Accepted in revised form: 15. 3.01