Description

• Proteinuria: urinary protein excretion of >150 mg/day
• Nephrotic-range proteinuria: Urinary protein excretion of ≥3.5 g/day; also called heavy proteinuria

Pediatric Considerations

• Proteinuria: Normal is daily excretion of up to 100 mg/m² (body surface area) for children. For neonates, daily excretion may be up to 300 mg/m2 due to decreased reabsorption of filtered proteins.
• Nephrotic-range proteinuria: daily excretion of >1,000 mg/m² (body surface area)

Pregnancy Considerations

• Proteinuria in pregnancy >20 weeks’ gestation is a hallmark of preeclampsia/eclampsia and demands further workup.
• Proteinuria in pregnancy before 20 weeks’ gestation is suggestive of underlying renal disease.

Epidemiology

Prevalence
The prevalence of proteinuria varies based on the definition used; maybe as high as 10% in school-aged children

Etiology and Pathophysiology

Normal protein filtration up to 150 mg/day, of which approximately 20 mg is albumin

• Glomerular proteinuria: increased glomerular capillary wall permeability due to both the increased size of glomerular basement membrane pores and loss of negatively charged barrier from glycosaminoglycans
  • Primary glomerulonephropathy
    • Minimal-change disease
    • Idiopathic/primary membranous glomerulonephritis
    • Focal segmental glomerulosclerosis/glomerulonephritis
    • Membranoproliferative glomerulonephritis
    • IgA nephropathy (Berger disease)
  • Secondary glomerulonephropathy
    • Chronic disease (diabetes, hypertension, chronic kidney disease)
    • Autoimmune/collagen vascular disorders (e.g., lupus nephritis, Henoch-Schönlein purpura, Goodpasture syndrome)
    • Genetic disorders (Alport syndrome, Fabry disease)
    • Amyloidosis, sarcoidosis
    • Preeclampsia
    • Infection (HIV, CMV, hepatitis B and C, poststreptococcal, endocarditis, syphilis, malaria)
    • Malignancy (GI, lung, lymphoma)
    • Renal transplant rejection
    • Structural (reflux nephropathy, polycystic kidney disease)
    • Drug-induced (NSAIDs, penicillamine, lithium, heavy metals, gold, heroin)
    • Sickle cell disease
• Tubulointerstitial proteinuria: Tubulointerstitial disease prevents proximal tubular reabsorption of smaller proteins (β₂-microglobulin, immunoglobulin [Ig] light chains, retinol-binding protein, amino acids).
  • Medications (NSAIDs, aminoglycosides, penicillins, cephalosporins, quinolones, sulfonamides, amphotericin B, cisplatin, radiocontrast media)
  • Toxins (lead, copper, mercury)
  • Uric acid nephropathy
  • Interstitial nephritis
  • Fanconi syndrome
  • Acute tubular necrosis
• Overflow proteinuria: Plasma concentration of low-molecular-weight proteins exceed capacity of the tubules to reabsorb filtered protein.
  • Multiple myeloma (light chains; also tubulotoxic)
  • Hemoglobinuria
  • Myoglobinuria (in rhabdomyolysis)
  • Lysozyme (in acute monocytic leukemia)
• Benign proteinuria
  • Functional (fever, exercise, cold exposure, stress, dehydration, seizures, CHF)
  • Idiopathic transient
  • Orthostasis (postural)—usually found in older children and adolescents

General Prevention

Control of weight, BP, and blood glucose reduces the risk of chronic disease that leads to proteinuria.

Commonly Associated Conditions

Nephrotic syndrome, glomerulonephritis, chronic kidney disease