Haematuria without diagnosis? Think about the rare causes…

Abstract

We describe a case of a 17-year-old man admitted in the emergency room with a 2-month history of intermittent macroscopic haematuria and left lumbar pain. Physical examination and vital signs were normal. Investigation indicated a recurrent non-glomerular haematuria. The Doppler ultrasound revealed a compression of the left renal vein with upstream dilatation which was subsequently confirmed by CT angiography. These findings are in keeping with a case of nutcracker syndrome (NutS). Although asymptomatic in most cases, it can be a rare cause of haematuria. The teenager was referred to paediatric nephrology and was treated conservatively with spontaneous resolution of macroscopic haematuria. With this case, we would like to highlight that in children or adolescents with haematuria without an apparent cause, a high level of suspicion and appropriate imaging are necessary for the diagnosis of NutS.

Background

Macroscopic haematuria in children or adolescents is a common cause of admission to the emergency department with a long list of differential diagnoses, including urinary tract infections, hypercalciuria, nephrolithiasis, glomerulonephritis.^1–3 In the most cases, the diagnosis is straightforward with a typical history, physical examination findings and laboratory results.^{3 4} Extensive workup may be required in rare cases.^{2 3}

The nutcracker syndrome (NutS) is a vascular compression disorder that occurs when the left renal vein (LRV) becomes compressed in its trajectory, mostly between the abdominal aorta (AA) and the superior mesenteric artery (SMA), or less frequently between the aorta and the lumbar spine.^1–8 The first and most frequent form is designated anterior NutS and the second posterior NutS, respectively.^{3 4} This syndrome is a rare, probably underdiagnosed cause of recurrent non-glomerular haematuria in children and adolescents.2 3 5 7 Its prevalence is unknown.^{5 7}

Typically, it manifests between the third and fourth decade, but it can be diagnosed at any age with a slight female predominance.^{4 5 7} This is a diagnosis which requires a high index of clinical suspicion and can be confirmed by imaging.^1–7

We report a case of anterior NutS in a 17-year-old man who presented with intermittent macroscopic haematuria and left lumbar pain. The case clearly demonstrates the diagnostic challenge in evaluating an adolescent with haematuria and the importance of a methodical and systematic approach.

Case presentation

A 17-year-old male adolescent was admitted to the hospital with a 2-month history of intermittent macroscopic haematuria and left lumbar pain (short duration episodes with spontaneous resolution).

A week prior to presentation, he also had pollakiuria without dysuria. There was no history of fever, fatigue, abdominal pain, oedema, recent infection or abdominal trauma. He also denied the practice of unsafe sex. Medical history revealed that he had recurrent wheezing episodes as a child, and he started isotretinoin 6 weeks ago because of acne. There was no relevant family history (including macroscopic haematuria or hearing deficit).

General examination was unremarkable with slight acne, a normal blood pressure, no oedema, normal genital area (without varicocele), Tanner stage 5 and a body mass index (BMI) of 19.1 kg/m² (15th centile).

Investigations

In the emergency room, urine was collected and macroscopic haematuria was observed (ruby red colour), without clots. In order to exclude the most frequent causes of haematuria in adolescence, a general laboratory evaluation was performed (blood count, coagulation, renal function, complement levels, antistreptolysin O titre, urinalysis and urine culture) with normal results. Rapid antigen detection test for group A streptococcus was negative, renal and bladder ultrasound was normal (there were no masses, nephrolithiasis or morphological changes). Due to the absence of signs of severity, the adolescent was discharged with indication to suspend isotretinoin, and to do serial evaluation of urine at home (urinary dipstick) until further clinical and analytical evaluation in a future consultation.

On serial evaluation of the urine, oscillation in its colour was verified throughout the day (from yellow to ruby red colour, figure 1). The urinary dipstick varied from normal to showing presence of haematuria (3–4 plus) and proteinuria (0–2plus) with absence of leucocyturia and negative nitrites. In the urinalysis performed, the presence of dysmorphic erythrocytes or casts was never observed. Taking the above into consideration, it was concluded that this represented an intermittent, non-glomerular haematuria (figure 2).

Figure 1.

Changes in colour and urinary dipstick of two urine samples taken 2 hours apart. (A) Ruby red discolouration, with 4+ of haematuria and 2+ of proteinuria. (B) Clear urine with no changes in urinary dipstick.

Figure 2.

Causes of haematuria (glomerular or non-glomerular) according to urine characteristics.

The urinary protein: creatinine ratio and calcium: creatinine ratios were normal.

After the exclusion of the most frequent causes of non-glomerular haematuria (figure 3), the diagnosis of NutS was considered.

Figure 3.

Investigation diagram of macroscopic haematuria (local protocol). ANA, antinuclear antibody;TASO, anti-streptolysin O; UTI, urinary tract infection.

The Doppler ultrasound was suggestive of an anterior NutS (figure 4), presenting a 20° angle between the aorta and the SMA, with LRV tapering in its preaortic path (2 mm) and showing an upstream dilation (12.5 mm). CT angiography confirmed the diagnosis (figure 5).

Figure 4.

(A) Ultrasound demonstrating reduced calibre of left renal vein between AA and SMA; (B) permeability was maintained with Doppler ultrasound; (C) angle between AA and SMA was approximately 20°. AA, abdominal aorta; SMA, superior mesenteric artery.

Figure 5.

CT angiography demonstrating left renal vein compression between AA and SMA, with dilatation of LVR left upward from the compression site. AA, abdominal aorta; LRV, left renal vein; SMA, superior mesenteric artery.

Treatment

Management of NutS depends on the clinical presentation (severity and persistence of symptoms). Given the low severity of the condition in this case, we opted for conservative treatment. The patient was advised to gain weight, with the expectation of an increase in the retroperitoneal adipose tissue and hence reduction in LRV tension. The patient was also referred to nephrology.

Outcome and folow-up

The patient started exercising at the gym and sought out dietetic advise to optimise his diet, achieving good weight gain (current weight between 25 and 50th centiles). After 12 months of follow-up by nephrology and keeping a stable weight, with no further episodes of haematuria or lumbar pain, always normotensive and without any abnormal laboratory results, the adolescent was discharged by the nephrology team. He continued to be followed up regularly by his general practitioner, with a plan to refer back to nephrology if new symptoms or complications should arise.

Discussion

NutS is caused by the compression of the LRV between the AA and the SMA (anterior nutcracker), or between the AA and vertebral column (posterior nutcracker).4 5 8 9 There are also rare subtypes of NutS, including the compression of the LRV by a dilated left-sided inferior vena cava or right-sided NutS.^{8 9}

The aetiopathogenesis is not fully understood. Some theories include an abnormal origin of the SMA from the AA, an abnormally high course of the LRV, retroaortic or circumaortic variants of the LRV, posterior renal ptosis and a decrease in retroperitoneal fat with a consequent decrease in the aortomesenteric angle.3 4 6 7 9

Nutcracker phenomenon (NCP) is an asymptomatic finding of LRV entrapment and represents a normal variant (in the most cases), whereas NutS is a combination of clinical signs and symptoms that result from NCP.3–5 8–10

Clinical features of patients with NutS vary from microscopic haematuria to severe pelvic congestion syndrome.⁸ The most common symptoms are pelvic and/or lumbar/flank pain, gross or microscopic haematuria, orthostatic proteinuria (which may be in the nephrotic range), periurethral or gonadal varices (varicocele or ovarian vein syndrome) and orthostatic intolerance.^2–9 Pelvic congestion syndrome is characterised by symptoms of lower abdominal pain, dysuria, dysmenorrhoea, dyspareunia, varicocele and pelvic, vulval, gluteal, thigh or lower limb varices.⁸ Systemic manifestations have also been reported in individual cases including headache, tachycardia, abdominal pain, stomach ache, anxiety, emotional disturbances, chronic fatigue, syncope and fever.^{8 9}

NutS is rare but is probably an underdiagnosed cause of recurrent non-glomerular haematuria in children and adolescents with unremarkable history.^{2 3} Non-glomerular haematuria occurs due to the rupture of thin-walled veins of the adjacent renal calyx.^{2 4 6} The rupture is caused by the LRV pressure elevation secondary to its compression. Usually, the bleeding is self-limited, without haemodynamic repercussion or anaemia.⁴

NutS is difficult to diagnose unless there is a high clinical suspicion.^{2 3 9} The diagnosis depends on demonstration of compressed LRV with methods such as doppler ultrasound, CT or MR angiography and venography.^{2 4–10} A renal ultrasound with Doppler is the non-invasive investigation of choice, with a sensitivity and specificity of 69%–79% and 89%–100%, respectively.^3–10 It allows measurement of the anteroposterior diameter and the peak flow velocity of the LRV at two points (usually left from the aorta and at the compression point).^{4 7–9} Suggested cut-off value is 4.8 for peak velocity ratio.^{2 4 8} If required, confirmation can be done by CT or MR arteriography.3 4 7–9 These images allow a better definition of the anatomical relations and should be carefully reported. Renal biopsy is normal, if there is no association with other renal disease.²

Our patient had intermittent macroscopic haematuria, proteinuria and left lumbar pain, with no apparent cause at first evaluation. After excluding the most common causes of haematuria in adolescence, Doppler ultrasound was performed with suspicion of NutS and the diagnosis was confirmed with CT angiography.

The treatment of NutS must be individualised, based on the severity and persistence of symptoms.^{3 4}

Knowing that most cases in children (75%) resolve spontaneously (with growth, increasing BMI and alteration of kidney haemodynamic factors), a conservative approach is the first choice of treatment.^2–10 This was the evidence-based management in our particular case. However, if severe chronic pain, massive haematuria, chronic kidney disease or no improvement after more than 24 months are present, a surgical approach should be attempted. Surgical procedures include: intravascular or extravascular stents, intrapelvic chemical cauterisation, anterior nephropexy with excision of renal varicosities, LRV or SMA transposition, renal autotransplantation and gonadocaval bypass.^2–6

Learning points.

• Nutcracker syndrome (NutS) is a rare condition that requires a high level of suspicion in children or adolescent with recurrent haematuria, orthostatic proteinuria and/or lumbar/flank pain, especially when there is no apparent cause or clinical findings.

• Doppler ultrasound and CT angiography should be performed in such patients in order to avoid unnecessary renal biopsy.

• Treatment of NutS must be individualised, based on the severity and persistence of symptoms.

• In paediatric age groups, most cases resolve spontaneously and a conservative approach is the first choice of treatment.

• Surgical intervention is reserved for symptomatic and disabling NutS.