Proteinuria

Proteinuria is defined as a urinary protein excretion of > 150 mg/24 h. It has many possible causes, which may be benign (e.g., fever, intense exercise, dehydration) or more serious (e.g., glomerulonephritis, multiple myeloma). There are three different pathophysiological mechanisms that may lead to proteinuria: damage to the glomeruli (glomerular), damage to the tubules (tubular), or overproduction of low-molecular-weight proteins (overflow). If proteinuria is detected, patients should be further evaluated (e.g., additional urinalyses) to determine the underlying cause. The detection of microalbuminuria is of particular importance, as it suggests early diabetic or hypertensive nephropathy.

Proteinuria = urinary protein excretion of > 150 mg/24 h

Urinalysis

• Urine dipstick: repeat to rule out transient proteinuria (primarily detects albumin)
• Sulfosalicylic acid test: sulfosalicylic acid is added to urine to measure total urine proteins (not specific for albumin)
• 24-hour urine collection or urine protein-to-creatinine ratio in a spot urine sample to rule out orthostatic proteinuria
• Urine sediment to rule out glomerular disease
• Electrophoresis; to rule out tubulointerstitial diseases and multiple myeloma

Proteinuria can cause foamy urine.

Diagnosis of underlying disease

• See “Differential diagnoses of nephrotic syndrome.”
• See “Diabetes mellitus.”
• See “Multiple myeloma.”

References:^[1]

According to quantity

Moderately increased albuminuria (formerly microalbuminuria)

• Urine albumin excretion of 30–300 mg/24 h
• Diagnosis is made if two out of three tests are positive.
• Early symptom of diabetic nephropathy and hypertensive nephropathy
• Specific urine dipstick tests; , radioimmunoassay, or ELISA required for detection

Severely increased albuminuria (formerly macroalbuminuria)

• Urine albumin excretion > 300 mg/24 h
• Standard urine dipstick tests can be used for detection.
• Nephrotic syndrome: massive proteinuria (> 3.5 g/24 h), hypoalbuminemia, edema, and hyperlipidemia

According to origin

Glomerular proteinuria ^[2][3]

• Damage to the glomeruli → increased permeability of the glomerular filtration barrier → urinary protein excretion
• Characteristic finding: appearance of large proteins in the urine
  • Selective glomerular proteinuria
    • Loss of negative charge of glomerular basement membrane
    • Only small- to medium-sized proteins can be found in the urine (primarily albumin)
    • Can be found in diseases with mild damage to the glomeruli (e.g., minimal change disease, IgA nephropathy)
  • Non-selective glomerular proteinuria
    • Damage to the glomerular basement membrane
    • All types of protein of any size can be found in the urine (albumin, transferrin, and IgG are commonly detected)
    • Can be found in diseases with severe damage to the glomeruli and subsequent permeability to all components of the blood (e.g., rapidly progressive glomerulonephritis, lupus nephritis, amyloid nephropathy)

Tubular proteinuria

• Damage to the tubules → failure to reabsorb small proteins in the tubules → urinary protein excretion
• The detection of beta-2 microglobulin without large proteins is typical.
• Can be found in tubulointerstitial nephritis, analgesics nephropathy, acute renal failure

Mixed proteinuria

• Found in diseases that affect both the glomeruli and the tubules (e.g., chronic renal failure)

Prerenal proteinuria (or overflow proteinuria)

• Increased production of low-molecular-weight proteins → The reabsorption capacity of the tubules is exceeded.
  • Light chains or Bence-Jones protein (see myeloma kidney)
  • Hemoglobinuria (in hemolysis)
  • Myoglobinuria (in rhabdomyolysis)

Postrenal proteinuria

• Proteins that are being produced in the tubules (Tamm-Horsfall protein)
• Proteins that reach the urine in the lower urinary tract (e.g., trauma or inflammation)

• Defined as isolated proteinuria < 3.5 g/24 h
• Important, benign differential diagnosis in the evaluation of proteinuria
• Very common; mostly affects younger individuals
• Types of benign proteinuria
  • Orthostatic proteinuria (postural proteinuria): increased protein excretion only in the upright position
  • Transient proteinuria
    • Most common cause of isolated proteinuria in children
    • Causes:
      • Heavy exertion/stress
      • Fever
      • Seizures
      • Exposure to cold temperatures
  • Women can present with mild proteinuria due to vaginal discharge.
• A dipstick test should be repeated to exclude underlying disease.
• No treatment necessary; excellent prognosis