Description

Urinary protein excretion of >150 mg/day

• Nephrotic-range proteinuria: urinary protein excretion of >3.5 g/day; also called heavy proteinuria
• Three pathologic types:
  • Glomerular proteinuria: increased permeability of proteins across glomerular capillary membrane
  • Tubular proteinuria: decreased proximal tubular reabsorption of proteins
  • Overflow proteinuria: increased production of low-molecular-weight proteins

Pediatric Considerations

• Proteinuria: Normal is daily excretion of up to 100 mg/m² (body surface area).
• Nephrotic-range proteinuria: daily excretion of >1,000 mg/m² (body surface area)

Pregnancy Considerations

• Proteinuria in pregnancy beyond 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.

Etiology and Pathophysiology

• Glomerular proteinuria: increased filtration/larger proteins (albumin) due to the following:
  • Increased size of glomerular basement membrane pores and
  • Loss of proteoglycan negative charge barrier
• Tubular proteinuria: Tubulointerstitial disease prevents proximal tubular reabsorption of smaller proteins (β₂-microglobulin, immunoglobulin [Ig] light chains, retinol-binding protein, amino acids).
• Overflow proteinuria: proximal tubular reabsorption overwhelmed by increased production of smaller proteins
• Glomerular proteinuria
  • Primary glomerulonephropathy
    • Minimal change disease
    • Idiopathic/primary membranous glomerulonephritis
    • Focal segmental glomerulonephritis
    • Membranoproliferative glomerulonephritis
    • IgA nephropathy
  • Secondary glomerulonephropathy
    • Diabetic nephropathy
    • Autoimmune/collagen vascular disorders (e.g., lupus nephritis, Goodpasture syndrome)
    • Amyloidosis
    • Preeclampsia
    • Infection (HIV, 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)
• Tubular proteinuria
  • Hypertensive nephrosclerosis
  • Tubulointerstitial disease (uric acid nephropathy, hypersensitivity, interstitial nephritis, Fanconi syndrome, heavy metals, sickle cell disease, NSAIDs, antibiotics)
  • Acute tubular necrosis
• Overflow proteinuria
  • Multiple myeloma (light chains; also tubulotoxic)
  • Hemoglobinuria
  • Myoglobinuria (in rhabdomyolysis)
  • Lysozyme (in acute monocytic leukemia)
• Benign proteinuria
  • Functional (fever, exercise, cold exposure, stress, CHF)
  • Idiopathic transient
  • Orthostasis (postural)

Genetics
No known genetic pattern

Risk Factors

• Hypertension
• Diabetes
• Obesity
• Strenuous exercise
• CHF
• UTI
• Fever

General Prevention

Control of weight, BP, and blood glucose reduces the risk of proteinuria.

Commonly Associated Conditions

• Hypertension (common)
• Diabetes mellitus (DM) (common)
• Preeclampsia (common)
• Multiple myeloma (rare)