Proteinuria

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Basics

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)

Risk Factors

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

Genetics
No known genetic pattern

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)

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