Orthostatic proteinuria

Orthostatic proteinuria (postural proteinuria) is defined as normal urinary protein excretion during the night but increased excretion during the day, associated with activity and upright posture. Total urinary protein excretion may be increased but levels above 1 g per 24 hours are more likely to be associated with underlying renal disease. The exact cause of orthostatic proteinuria is not known.

Epidemiology¹

• It is most common in children and young adults and most common in young adult males.

• The prevalence is 2-5% of adolescents and rare in those older than 30 years.

Presentation

• Positive urinary protein dipstick tests during the day but negative tests with early morning urine.

• All other investigations of renal function and urinary tract anatomy are normal.

Differential diagnosis

Other causes of proteinuria include:

• Physical exercise.

• Fever.

• Pregnancy.

• Urinary tract infection.

• Nephrotic syndrome.

• Renal tubular disease.

• Orthostatic proteinuria may be due to the nutcracker phenomenon (compression of the left renal vein between the aorta and the superior mesenteric artery)^{2 3} .

• Chronic renal disease - eg, diabetic kidney disease, glomerulonephritis, reflux nephropathy, systemic lupus erythematosus and amyloidosis.

The symptoms associated with the nutcracker phenomenon vary from asymptomatic haematuria to severe pelvic congestion. Symptoms include haematuria, orthostatic proteinuria, flank pain, abdominal pain, varicocele, dyspareunia, dysmenorrhoea and fatigue⁴ .

Investigations¹

• Urinalysis: initial check for possible urinary tract infection (urinary nitrite, leukocytes), diabetes (glycosuria) or other possible causes of proteinuria.

• Quantifying proteinuria: 24-hour urine collection for protein, creatinine clearance and differential urinary protein are the best method. The 24-hour collection should be split into two separate collections for overnight and daytime.

• Alternatively, the urinary albumin:creatinine ratio from overnight and daytime urine samples can be compared.

• Normal night-time protein excretion with increased protein excretion during the day are indicative of orthostatic proteinuria. However, a further assessment of other causes of proteinuria is essential if there is any doubt.

• Midstream urine: microscopy, culture and sensitivities if a urinary tract infection is suspected.

• Blood tests: U&Es, blood glucose, serum proteins.

• Several imaging methods such as Doppler ultrasound, CT angiography, MR angiography and retrograde venography are used to diagnose the nutcracker syndrome⁴ .

• Imaging of the urinary tract may be required.

• Renal biopsy is indicated if there are signs of vasculitis, active urinary sediments, hypertension, persistent or gross haematuria, renal insufficiency, or hypocomplementaemia.

Management

It is essential to rule out any other cause of persistent proteinuria and this will often require referral to a nephrologist.

The management of nutcracker syndrome depends on the clinical presentation and the severity of the left renal vein hypertension. The treatment options range from surveillance to nephrectomy.

Prognosis

• The long-term prognosis of true orthostatic proteinuria is excellent.

• Although many of the patients continue to have proteinuria of minor degree for several decades, they do not get hypertension or renal impairment.

• The prognosis of nutcracker syndrome depends on the degrees of left renal vein compression, left renal vein hypertension and the compensatory development of collateral blood vessels⁴ .