What Causes Proteinuria?

Patient Presentation
A 16-year-old female came to clinic because of 2 days of dysuria. She was having some increased frequency and also pain with urination. She wasn’t sure if the pain began with the bladder contracting or when her urine stream touched her genital area. She denied fever, chills, nausea, emesis, constipation or pain with defecation. She also denied previous bladder infections or sexual activity. The family history was negative for renal disease or hearing problems. The social history showed her to be a cross-country runner who had increased her mileage the past week by almost 50%. The review of systems was negative.

The pertinent physical exam showed a healthy female with no distress. Her blood pressure was 106/62, pulse of 68 and respiratory rate of 16. She was afebrile and her growth parameters showed a weight of 25%, and height of 75%, consistent with previous measurements. Her abdomen examination was negative including no suprapubic or costovertebral angle tenderness. Genitourinary examination revealed diffuse erythema of the vaginal area and perineum.

The diagnosis of skin irritation due to contact with sweat and clothing friction was made. The patient was advised to change into clean clothing often, not tuck her shirt into her pants to help keep moisture away from the genital area and to use sports lubrication products to decrease the friction from her clothing. Because a bladder infection could not be fully ruled-out a laboratory evaluation of a urine dip was done and showed a specific gravity of 1.015, 2+ protein and negative leukocyte esterase and blood. Because of the protein, the physician reviewed her chart more closely and saw normal blood pressure readings and also a BUN and creatinine that were normal during an emergency room visit for head trauma The physician thought that the proteinuria was most likely due to the increase in exercise. The patient’s clinical course over the next few weeks found none to 1+ protein in the urine, and which resolved after the cross-country season finished.

Proteinuria occurs relatively often in pediatric practice with 5-15% of school children having transient proteinuria, the most common cause. However, proteinuria can be a sign of kidney disease. Therefore, it is important to evaluate the proteinuria in light of the clinical situation. A good history and physical examination along with a full urinalysis and/or BUN and creatinine, or urine protein/creatinine ratio may be all that is necessary. Another patient with edema, hypertension or hematuria needs a fuller evaluation and treatment. Proteinuria is usually categorized into three groups to assist with evaluation and treatment and they include: transient, orthostatic or persistent.

Transient means just that. It occurs only during the inciting problem and remits afterwards. It generally is < 2+ on a dipstick. Proteinuria due to fevers usually resolves in 10-14 days, and exercise induced proteinuria remits within 48 hours of the exercise.

Orthostatic (postural) proteinuria is proteinuria that occurs in the upright position only. It can be intermittent or persistent. It is the most common cause of asymptomatic proteinuria in children especially adolescents. Protein excretion in the recumbent position is < 4 mg/m2/hr and in the upright or ambulatory position is 2-4 times this amount.

Persistent asymptomatic isolated proteinuria occurs in children and laboratory and clinical testing is otherwise normal. The protein is monitored every 6-12 months and if protein is rising then renal biopsy may be indicated. Glomerular diseases all have proteinuria. One of the most common in children is nephrotic syndrome due to minimal change disease. Nephrotic syndrome has the following characteristics: proteinuria, hypoalbuminemia, hypercholesterolemia and edema.

An urine dipstick is often used to interpret proteinuria. The amounts of protein are shown here:

Trace = 10-20 mg/dL
1+ = 30 mg/dL
2+ = 100 mg/dL
3+ = 300 mg/dL
4+ = 1000-2000 mg/dL

“A urine sample is positive for protein if the dipstick is [> or =] 1+ on a urine sample with a specific gravity of [ 1.015, the dipstick must be [> or =] 2+ to be considered positive.”

Learning Point
The differential diagnosis of proteinuria includes:

  • Transient proteinuria
    • Cold exposure
    • Congestive heart failure
    • Epinephrine administration
    • Exercise
    • Fever
    • Seizures
    • Serum sickness
  • Orthostatic
  • Persistent asymptomatic isolated proteinuria
    • Glomerular disease
      • Nephrotic syndrome, minimal change
      • Alport syndrome
      • Glomerulonephritis
        • Membranoproliferative
        • Post-infectious
      • Henoch-Schonlein purpura
      • HIV-associated nephropathy
      • IgA nephropathy
      • Sickle cell anemia
      • Systemic lupus erythematosus, nephritis
      • Vasculitis
    • Tubulointerstitial disease
      • Fanconi anemia
        • Dent’s disease
      • Interstitial nephritis
      • Ischemia
      • Reflux nephropathy
      • Renal dys- or hypoplasia
      • Medications
        • Aminoglycosides
        • Lithium
        • Penicillin

Questions for Further Discussion
1. What are indications for renal biopsy with proteinuria?
2. What are causes of falsely-positive proteinuria on dipstick?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Urine and Urination and Kidney Diseases.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Ariceta G. Clinical practice: Proteinuria. Eur J Pediatr. 2011 Jan;170(1):15-20.

Hladunewich MA, Schaefer F. Proteinuria in special populations: pregnant women and children. Adv Chronic Kidney Dis. 2011 Jul;18(4):267-72.

Kaplan BS, Pradhan M. Urinalysis interpretation for pediatricians. Pediatr Ann. 2013 Mar;42(3):45-51.

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Systems Based Practice
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.


    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital