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

CLINICAL FEATURES

Clinical features of patients with NCS are various. The symptoms vary from asymptomatic hematuria to severe pelvic congestion. Some patients have severe and persistent symptoms. Symptoms are aggravated by physical activity^[7]. Symptoms include hematuria, orthostatic proteinuria, flank pain, abdominal pain, varicocele, dyspareunia, dysmenorrhea, fatigue and orthostatic intolerance^[11-13]. The symptoms of autonomic dysfunction such as hypotension, syncope, and tachycardia could be seen but they are rare^[14]. Henoch-Schönlein purpura, IgA, nephropathy, membranous nephropathy, and idiopathic hypercalciuria with nephrolithiasis associated with NCS have been reported^[12,15].

NCS can differentiate clinically into 2 subtypes as follows: typical presentation (or renal presentation) and atypical presentation (or urologic presentation). Typical clinical presentation include hematuria (micro- to macrohematuria), orthostatic proteinuria with or without flank pain. Abdominal pain, varicocele, dyspareunia, dysmenorrhea, fatigue and orthostatic intolerance are the components of the atypical presentation (Table 1).

The most common symptom is hematuria. It is due to elevated LRV pressure resulting in the rupture of thin-walled septum between the varices and the collecting system in the renal fornix. Hematuria varies from micro- to macrohematuria. LRV is correspondent in this variation^[14]. Isolated hematuria was reported 33.3% in children with NCS. Microhematuria is 4 times more common than macrohematuria^[16].

Orthostatic proteinuria is another common symptom in NCS. The degree of proteinuria is variable. The incidence of orthostatic proteinuria is high during puberty. The mechanism of orthostatic proteinuria was not well understood yet. Changes of renal hemodynamic and the elevated levels of norepinephrine and angiotensin II were thought as the causes^[17].

Pain is a result of the inflammatory cascade triggered by venous hypertension. Flank pain and abdominal pain are the consequences of that inflammatory process^[1]. Left flank pain can be due also to urethral colic related to blood clots passing down to left ureter^[7].

Varicocele affects 5.5%-9.5% of men and usually occurs on the left side. Development of varicocele is related with high LRV pressure and collateral circulation. Collateral veins could be demonstrated on pelvic and abdominal Doppler ultrasonography or venography^[11].