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.

Epidemiology

• 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).¹
• Chronic renal disease, e.g. diabetic kidney disease, glomerulonephritis, reflux nephropathy, systemic lupus erythematosus and amyloidosis.

Investigations

• 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.
• Doppler is the preferred examination in screening for the nutcracker phenomenon.²
• Other investigations include: imaging of the urinary tract; renal biopsy may be required if the diagnosis remains in doubt.

Management

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

Prognosis

• The long-term prognosis 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.
• One study following up patients with orthostatic proteinuria over 20 years found no evidence of renal disease.³
• However, there have been occasional reports of a diagnosis of orthostatic proteinuria being followed by glomerular disease with nephritic syndrome and progressive renal disease.⁴

Document references

1. Ha TS, Lee EJ; ACE inhibition can improve orthostatic proteinuria associated with nutcracker syndrome. Pediatr Nephrol. 2006 Nov;21(11):1765-8. Epub 2006 Aug 11. [abstract]
2. Barbey F, Venetz JP, Calderari B, et al; Orthostatic proteinuria and compression of the left renal vein (nutcracker syndrome). Presse Med. 2003 May 31;32(19):883-5. [abstract]
3. Springberg PD, Garrett LE Jr, Thompson AL Jr, et al; Fixed and reproducible orthostatic proteinuria: results of a 20-year follow-up study. Ann Intern Med. 1982 Oct;97(4):516-9. [abstract]
4. Berns JS, McDonald B, Gaudio KM, et al; Progression of orthostatic proteinuria to focal and segmental glomerulosclerosis. Clin Pediatr (Phila). 1986 Mar;25(3):165-6. [abstract]

Internet and further reading

• Proteinuria, The Renal Association

Acknowledgements