|Year : 2021 | Volume
| Issue : 1 | Page : 36-39
Exercise-induced gross hematuria due to concurrent nutcracker syndrome and immunoglobulin a nephropathy
Eugene Yu-hin Chan1, Kevin Kin-Fen Fung2, Tsz Wai Ho1, Elaine Yee-ling Kan2, Alison Lap-tak Ma1
1 Department of Paediatrics, Paediatric Nephrology Centre, Hong Kong, China
2 Department of Radiology, Hong Kong Children's Hospital, Hong Kong, China
|Date of Submission||01-Oct-2020|
|Date of Decision||08-Jan-2021|
|Date of Acceptance||24-Mar-2021|
|Date of Web Publication||30-Jun-2021|
Eugene Yu-hin Chan
Paediatric Nephrology Centre, Department of Paediatrics, Hong Kong Children's Hospital, Hong Kong
Source of Support: None, Conflict of Interest: None
We describe a patient presenting with loin pain and recurrent exercise-induced hematuria who concurrently had immunoglobulin A (IgA) nephropathy and nutcracker syndrome. While the diagnosis of IgA nephropathy did not fully explain the clinical symptoms, initial computed tomography was unrevealing. Renal venography eventually confirmed the presence of nutcracker syndrome.
Keywords: Exercise hematuria, hematuria, nutcracker phenomenon, renal venography
|How to cite this article:|
Chan EY, Fung KK, Ho TW, Kan EY, Ma AL. Exercise-induced gross hematuria due to concurrent nutcracker syndrome and immunoglobulin a nephropathy. Asian J Pediatr Nephrol 2021;4:36-9
|How to cite this URL:|
Chan EY, Fung KK, Ho TW, Kan EY, Ma AL. Exercise-induced gross hematuria due to concurrent nutcracker syndrome and immunoglobulin a nephropathy. Asian J Pediatr Nephrol [serial online] 2021 [cited 2022 Jul 5];4:36-9. Available from: https://www.ajpn-online.org/text.asp?2021/4/1/36/320186
| Introduction|| |
Nutcracker syndrome is caused by the direct compression of the left renal vein by the superior mesenteric artery and the aorta, and patients develop clinical features including gross hematuria, orthostatic proteinuria, flank or pelvic pain, varicocele (in boys), or pelvic congestion syndrome (in girls). Elevated pressure leads to venous reflux and varices between renal pelvis and ureter, which following rupture of the thin-walled septum, results in hematuria. Immunoglobulin A (IgA) nephropathy often presents with hematuria and variable degree of proteinuria, with IgA dominant or codominant deposits, predominantly in the mesangium. The condition is described across all age groups and is particularly prevalent in Asia. We report here a patient presenting with recurrent exercise-induced hematuria who showed the features of both nutcracker syndrome and IgA nephropathy.
| Case Report|| |
A 17-year-old Chinese boy presented with recurrent painless gross hematuria for 2 months. Hematuria was precipitated by mild exertion, lasted throughout the urinary stream and was intermittently associated with left loin pain. The patient did not report frothy urine, dysuria, or stone passage. There was no history of trauma or sports participation. Family history was unremarkable. His body mass index was 17.5 kg/m2 and blood pressure was 100/53 mm Hg. Physical examination was otherwise unremarkable.
Urinalysis revealed more than 50 eumorphic red blood cells per mm3 of urine; there were no crystals or casts or hypercalciuria. While there was no hypercalciuria, urine albumin in the early morning sample was 4.8 mg/mmol (normal <3 mg/mmol); proteinuria was not orthostatic. Serum albumin (46 g/L; normal range 33–48 g/L), creatinine (64 μmol/L; normal 60–100 μmol/L), and estimated glomerular filtrate rate (103 mL/min per 1.73 m2) were normal. Other laboratory tests, including complete blood count, clotting profile, creatinine kinase, urate, anti-streptolysin O titer, autoimmune markers, and complement level, were normal. Abdominal radiography did not reveal kidney stone or nephrocalcinosis. A Doppler ultrasound performed at an outside institute was unremarkable. Computed tomography with contrast did not demonstrate evidence of left renal vein compression; both aorto-mesenteric angle and ratio of left renal vein diameter were normal. Kidney biopsy showed IgA nephropathy with focal mesangial hypercellularity with Oxford classification of M1E0S0T0C0 on light microscopy and granular IgA mesangial deposits on immunofluorescence [Figure 1].
|Figure 1: (a and b) Kidney biopsy showing representative glomerulus with mild increase in mesangial matrix and cellularity on (a) hematoxylin and eosin and (b) periodic acid Schiff stain. (c) Immunofluorescence study shows diffuse global granular immunoglobulin A deposits in the mesangium. (Original magnification ×400)|
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Since a diagnosis of IgA nephropathy could not explain the loin pain associated with recurrent gross hematuria, we decided to re-investigate for nutcracker syndrome. Renal venography demonstrated an indentation upon the mid-portion of the left renal vein [Figure 2]a. The venous pressure at the distal left renal vein and the inferior vena cava was 9 and 4 mm Hg, respectively [Figure 2]b and [Figure 2]c, indicating a pressure gradient of 5 mm Hg, which was elevated (normal range <3 mm Hg). These findings supported a diagnosis of nutcracker syndrome. A repeat ultrasound indicated narrow aorto-mesenteric angle in the standing position which became normal during deep inspiration [Figure 2]d and [Figure 2]e.
|Figure 2: (a). Diagnostic left renal vein venogram showed an abnormal indentation at the aorto-mesenteric portion of left renal vein (white triangles) and slowing of contrast flow into the proximal portion of left renal vein, indicating narrowing of left renal vein due to compression by the superior mesenteric artery. (Left kidney outline annotated by white dash line). (b) Pressure measurements performed with catheter tip located at inferior vena cava and (c) with catheter tip located at distal left renal vein. Venous pressure at inferior vena cava was 4 mm Hg and that at distal left renal vein was 9 mm Hg, indicating a pressure gradient of 5 mm Hg, which was diagnostic of nutcracker syndrome. Note that in (b) the catheter tip was positioned beyond the expected compression area by the superior mesenteric artery. Dynamic ultrasound performed (d) in the standing position showed narrowed aortomesenteric angle (13.8°; normal 38°–65°) and (e) with deep inspiration showed normal aortomesenteric angle measuring 47°|
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Our patient was administered angiotensin-converting enzyme inhibitor which led to improvement of albuminuria. Conservative measures, such as weight gain, were advised for the management of nutcracker syndrome. However, he continued to experience recurrent gross hematuria and was referred to vascular surgeons for possible intervention following failure of a year of conservative management.
| Discussion|| |
We described an interesting patient with underlying IgA nephropathy who presented with recurrent exercise-induced hematuria due to nutcracker syndrome. The initial computed tomography failed to demonstrate the features of nutcracker syndrome. We postulate this could be due to the deep inspiratory effort which the patient was instructed to take during scanning. The “pseudo-normalization” of aorto-mesenteric angle may be related to the widening of distance between the superior mesenteric artery and aorta during deep inspiration. This finding has not been described in the literature but was reproduced in our second look ultrasound. Renal venography eventually confirmed the presence of nutcracker syndrome.
Exercise-induced hematuria may follow the various forms of exercise. Direct injury to the kidneys and/or bladder was unlikely since our patient was not engaged in contact sports. Nontraumatic exercise-induced hematuria can be caused by various potential mechanisms, such as renal ischemia due to blood redistribution. This type of exercise-induced hematuria is often influenced by exercise duration and intensity. Our patient experienced an exacerbation even after mild exertion, making this etiology unlikely. Of note, our patient had concurrent nutcracker syndrome and IgA nephropathy. This association has been described in the literature, although a causal relationship between renal vein entrapment and secondary kidney damage due to venous congestion remains to be delineated. Besides, IgA nephropathy is particularly common among the Asian population. While there was no specific reported incidence in our population, the incidence of pediatric IgA nephropathy was 4.5 per 100,000 patient year in a Japanese biopsy registry. IgA nephropathy can result in gross hematuria, but it is mostly infection triggered. Another important differential diagnosis, in this case, would be nutcracker syndrome. It is most prevalent in young patients in their second or third decade of life, which may be related to a rapid height gain during puberty and narrowing of the aortomesenteric angle. However, the incidence of nutcracker syndrome remains unknown due to variable symptoms and a lack of consensus on diagnostic criteria.
The radiological features of nutcracker syndrome include left renal vein compression, elevated left renal vein diameter ratio (renal hilar to aortomesenteric portions), and narrowed aortomesenteric angle. In addition to these morphological features, Doppler ultrasound provides additional dynamic information and is the most commonly used modality due to its lack of radiation. However, the procedure is highly operator dependent and technically challenging. The reported sensitivity and specificity ranged from 69% to 90% and 89% to 100%, respectively. Kim et al. evaluated the diagnostic values of computed tomography as compared to renal venography. Both the beak sign (abrupt triangular left renal vein narrowing with an acute angle at the aortomesenteric portion) and a left renal vein diameter ratio demonstrated the greatest diagnostic accuracy with an area under the curve of 0.90 on receiver operating characteristic analysis. While magnetic resonance imaging is less utilized for nutcracker syndrome, Er et al. found it useful for the diagnosis and follow-up. If the diagnosis is equivocal, renal venography with pressure measurement can be performed. While the renocaval pressure gradient is <1 mm Hg in the normal population, the gradient increases to more than 3 mm Hg when the left renal vein is compressed.,
The management of nutcracker syndrome in children remains controversial. Conservative therapy, including postural changes and avoidance of precipitating sports, is preferred as spontaneous resolution is possible., Weight gain is helpful as an increase in retroperitoneal adipose tissue may modify the position of the left kidney and reduce tension in the left renal vein. If symptoms fail to improve, therapeutic options include conventional surgery such as renal vein transposition or endovascular surgery such as percutaneous stenting., Optimized supportive therapy, including renin-angiotensin-aldosterone blockade, is important management in IgA nephropathy to slow kidney progression. The role of immunosuppression, however, remains controversial. In our patient, in view of a normal serum albumin level and a mild degree of albuminuria, we decided to manage the patient with angiotensin-converting enzyme inhibitors.
| Conclusion|| |
To conclude, nutcracker syndrome is an important cause of exercise-related recurrent hematuria in children. Although noninvasive imaging modalities are often helpful, the diagnostic yield may be affected by the patient's posture during the examination. Renal venography should be performed in cases with diagnostic difficulties. Additional conditions may co-exist and should be carefully looked for when the clinical picture cannot be fully explained by a particular diagnosis.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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