Proteinuria

Key Points Proteinuria on routine screening of children without symptoms most often is either orthostatic or transient, not pathological. Orthostatic (postural) proteinuria is most common. Transient proteinuria can result from stressors such as fever or vigorous exercise. Persistent (fixed) proteinuria can be asymptomatic, signaling underlying glomerular or tubular renal disease.

Nutcracker syndrome and phenomenon

Nutcracker syndrome describes symptomatology associated with obstruction to the left renal vein caused by pressure from the overlying superior mesenteric artery. Modern imaging methods show that some degree of left renal vein obstruction may be a common incidental finding in asymptomatic patients so it is better described as ‘nutcracker phenomenon’, NCP. The association of NCP with symptoms and signs is often speculative. NCP may be seen at any age but most patients with symptoms attributed to it are teenagers or young adults. The strongest evidence is for association with episodic macroscopic haematuria. There is weak evidence that it may in some circumstances account for orthostatic (postural) proteinuria, microscopic haematuria, or pain syndromes. Apart from rare examples of extreme haemorrhage the syndrome has not been associated with life-threatening features other than through complications of treatment. Various interventions have been employed, recently most commonly endovascular or extravascular approaches to stenting the vein, but serious adverse consequences from stent migration and thrombosis have been described.

Postural proteinuria (benign orthostatic proteinuria)

Postural proteinuria, synonymous with the condition known as benign orthostatic proteinuria, describes increased levels of protein excretion associated with normalization first thing in the morning. It is usually diagnosed in children, for whom it is the most common explanation for proteinuria picked up incidentally on dipstick testing. In children, it generally resolves with age and is thought to have a benign long-term prognosis, with the caveat that numbers with very long follow-up times are few. It is also seen in teenagers but becomes much less common in early adulthood. Its aetiology is not well understood, although patients with pathological causes for proteinuria and patients with physiological levels of total protein excretion have been shown to exhibit similar diurnal variation. Using currently published limits for daily protein excretion the diagnosis is common. Some examples have been attributed to nutcracker syndrome (compression of the left renal vein), although that is more commonly associated with macroscopic haematuria, and the association remains uncertain. The condition is best diagnosed by comparing first-in-morning urine samples paired with afternoon samples on several occasions. In childhood, if proteinuria levels are in the normal range in morning samples, and within moderately increased limits later in the day, probably no investigation beyond observation is required. Most will resolve; very few will evolve into serious renal disease. The simplest mode of long-term monitoring is to measure protein:creatinine or albumin:creatinine ratios in first-in-morning urine samples.