Name of journal: World Journal of Nephrology esps manuscript no: 11830 Columns: Minireviews Nutcracker syndrome

DIAGNOSIS

Variations of normal anatomy must be considered before the diagnosis. Asymptomatic dilatation of LRV is frequently seen on ultrasonography or computed tomography, has been accepted as a finding of a normal variant^[18]. NCS can exist without distended LRV. Normal flow also can exist in distended LRV^[11]. Therefore, the first diagnostic need must be clinical examination. Existence of the clinical features constitutes a basis for the diagnosis. The presence of macroscopic or microscopic hematuria and proteinuria must evaluate. Urine analysis, urine phase contrast microscopy, urine culture and imaging of kidneys should be performed. Several imaging methods are used to diagnose NCS. Doppler ultrasonography, computed tomography angiography (CTA), magnetic resonance angiography (MRA) and retrograde venography are utilized.

Doppler ultrasonography can be used as the first diagnostic test in patients with suspected NCS. Length of the LRV is 6 to 10 cm and the average normal LRV diameter is 4 to 5 mm^[7]. The normal pressure gradient between LRV and IVC is 1 mmHg or lower An elevated gradient > 3 mmHg between the LRV and the IVC can be used as a criteria of diagnosis for NCS^[5]. Diameter of normal left gonadal vein is approximately 3 mm^[19]. The normal superior mesenteric artery (SMA) originates behind the neck of the pancreas at the level of the first lumbar vertebra, and usually creates an acute angle at its origin from the aorta. Mean SMA angle is 51 ± 25º and mean SMA-aorta distance is 16 ± 6 mm in normal adults. Mean SMA angles in children are 45.8 ± 18.2º for boys and 45.3 ± 21.6º for girls. Mean SMA-aorta distances in children are 11.5 ± 5.3 mm for boys and 11.5 ± 4.5 mm for girls ^[20]. The standards of ultrasound diagnosis of NCS are descript by Zhang et al^[21]: (1) the flow velocity of stenosis of the LRV in the supine position accelerates remarkably, and the acceleration, which is more than 100 cm/s, is more obvious after the patient has stood for 15 min; (2) the inner diameter ratio between ratio between the renal hilum and stenosis of the LRV in the supine position is > 3 and is > 5 after the patient has stood for 15 min^[21]. Doppler ultrasonography has a sensitivity of 78% and a specificity of 100%^[22]. However, in children the use of these criteria is limited because the smallest LRV sampling area and the largest Doppler angle than in adults^[23].

CTA and MRA provide visualization of the anatomy. These tests can demonstrate the precise LRV compression point and/or prestenotic dilatation of the LRV together with perirenal and/or gonadal vein varices^[24]. “Beak sign” is the abrupt narrowing of the LRV with a triangular shape at the aortomesenteric portion. It might be most useful finding among the various CT parameters, because it showed sensitivity 91.7% and specificity 88.9%^[25]. MRA finding are similar to CT findings and MRA has the advantages of being less invasive with less amount of radiation than retrograde venography.

Retrograde venography is the gold standard for the diagnosis of NCS. It is not only confirming anatomic change, but also show a pressure gradient across the area of entrapment. Reflux of contrast into adrenal and gonadal veins from periureteral and perirenal venous collaterals, and pooling of contrast into the renal vein can be demonstrated^[22]. Retrograde venography is the most informative method although it is an invasive test. It is not commonly performed in patients who have not severe symptoms.

Another invasive test such as cystoscopy may be helpful to identify hematuria from left ureteral origin. Notching from varicosities of the renal pelvis and ureters may be seen^[26]. Cystoscopy is an indirect diagnostic method for NCS diagnosis.