Orthostatic Proteinuria

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Orthostatic proteinuria occurs in between 2-5% of all adolescents–it is primarily a pediatric condition, rarely occurring after age 30. Orthostatic proteinuria refers to the condition of an individual having proteinuria only while upright; the urine protein level returns to normal while lying down. I use the term “condition” rather than “disease” because orthostatic proteinuria carries with it a benign prognosis with no danger of worsening renal function.

In order to make a diagnosis of orthostatic proteinuria, one can obtain either a 24-hour urine collection, or one can do it using separate urine protein/creatinine ratios. If using the 24-hour urine collection, the first morning void is initially discarded. Then, a 16-hour upright collection is obtained between 7am-11pm; ideally, the patient should lie down 2 hours before finishing the upright collection, to avoid “contaminating” the supine collection with urine formed during the upright position. Then, a separate overnight 8-hour collection between 11pm-7am is obtained. In order for a diagnosis of orthostatic proteinuria to be made, there must be abnormal proteinuria (e.g., >100mg/16 hrs) during the upright collection but normal urine protein (e.g., during the overnight collection. Alternatively, spot urine protein/creatinine ratios from specimens taken first thing in the morning versus in the afternoon can be compared.

What is the pathogenesis of orthostatic proteinuria? There are several theories, though the precise etiology is not known. One possibility is that individuals with an exaggerated hemodynamic response to being in the upright position–manifested by increased secretion of angiotensin II and norepinephrine–might lead to transiently increased glomerular permeability to protein. Another theory is that some degree of “nutcracker syndrome”–in which the left renal vein is squeezed or kinked between the aorta and superior mesenteric artery–is at play more commonly in the upright position than while lying down.

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