Description

• Protein may be found in the urine of healthy children.
• The term proteinuria is used to indicate urinary protein excretion beyond the upper limit of normal (100 mg/m²/24 h or 4 mg/m²/h in children and 150 mg/24 h in adults).
  • Nephrotic-range proteinuria >1,000 mg/m²/24 h or 40 mg/m²/h
  • Nephrotic syndrome: nephrotic-range proteinuria with edema and hypoalbuminemia (<2.5 g/dL)
  • Microalbuminuria: elevated urinary excretion of albumin (30 to 300 mg/g albumin/creatinine ratio or 30 to 300 mg/24 h); generally used to indicate kidney disease in those with diabetes mellitus
• Classification
  • Persistent or fixed proteinuria
    • Urinary dipstick ≥1+ on the first morning urine specimen on ≥3 samples >1 week apart
    • Requires prompt referral to nephrology
  • Transient proteinuria
    • Proteinuria absent on subsequent urine examinations
    • It is not usually associated with clinically significant underlying renal disease.
    • May be associated with high fever, cold stress, dehydration, and exercise
  • Orthostatic or postural proteinuria
    • Elevated protein excretion when the patient is upright but normalizes when patient is supine
    • The most common cause of fixed or transient proteinuria in childhood and adolescence
    • Rarely exceeds 1 g/m²/24 h
    • Benign condition and not associated with edema

Epidemiology

Prevalence of asymptomatic proteinuria in school-aged children is 5.4–10.7% on single urine sample and <1% on ≥3 urine samples.

Pathophysiology

• Normally, ~50% urinary proteins are derived from tissue proteins and proteins from cells lining the urinary tract (i.e., Tamm-Horsfall protein).
• Proteinuria may be the result of glomerular proteinuria or tubular proteinuria.
• Glomerular proteinuria
  • An increased permeability of the glomeruli to the passage of plasma proteins
  • Large amounts of glomerular proteinuria may be found in the context of edema and hypoalbuminemia (nephrotic syndrome).
  • If there is hypertension, abnormal glomerular filtration rate, and hematuria, there may be nephritis as well.
• Tubular proteinuria
  • Decreased reabsorption of low-molecular-weight proteins by the proximal renal tubules
  • Rarely >1 g/24 h and is not associated with edema
  • The major marker is urinary β-2-microglobulin.
  • May be associated with other defects of proximal tubular function (e.g., renal tubular acidosis [RTA], glucosuria, phosphaturia, aminoaciduria) and tubular interstitial processes