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Proteinuria: Causes and Differential Diagnosis

Definitions of Proteinuria

Proteinuria is the presence of excess serum proteins in the urine.

Normal Protein Excretion:

Protein in the urine should be in the range of 50–150 mg in a 24-hour urine collection.

Functional Proteinuria:

Proteinuria, up to 500 mg/24 h, without the presence of kidney disease is called functional proteinuria. Causes are fever, exercise, orthostasis, exposure to heat and cold, heart insufficiency, or drugs.

Microalbuminuria:

Microalbuminuria is the presence of more than 30 mg and up to 300 mg albumin in a 24-h urine collection.

Selective Glomerular Proteinuria:

Selective glomerular proteinuria is the increased excretion of more than 300 mg medium-sized negatively charged proteins such as albumin in a 24-h urine collection.

Non-Selective Glomerular Proteinuria:

Non-selective glomerular proteinuria is the increased excretion of more than 3000 mg proteins of any size in a 24-h urine collection.

Tubular proteinuria:

Tubular proteinuria is the presence of more than 150 mg of small proteins (such as alpha 2-microglobulin) in a 24-h urine collection, while the serum proteins have normal concentrations.

Prerenal Proteinuria:

The increased concentration of small filtered proteins from the plasma leads to overtaxed tubular reabsorption (overflow proteinuria).

Postrenal Proteinuria:

Proteinuria from the upper urinary tract, bladder, prostate, or urethra.

Differential Diagnosis of Proteinuria

Functional Proteinuria:

• Fever
• Physical activity
• Heat or cold
• Heart failure
• Drugs

Microalbuminuria:

Microalbuminuria indicates an abnormal leakage of albumin in the renal glomerulus and is a sign of kidney damage:

• Diabetic nephropathy (stage III)
• Hypertensive Nephropathy
• Also possible in fever, after physical activity or due to infections.

Selective glomerular proteinuria:

Selective glomerular proteinuria indicates moderate glomerular damage:

• Glomerulonephritis (e.g., minimal-change GN)
• IgA-nephropathy
• EPH-gestosis
• Lupus nephritis with low activity

Non-selective glomerular proteinuria:

Non-selective glomerular proteinuria indicates severe glomerular damage:

• Glomerulonephritis
• Lupus nephritis
• EPH-gestosis
• Amyloidosis

Tubular proteinuria:

Small proteins are in part filtrated in the renal glomerulum and reabsorbed by tubular cells. Tubular proteinuria indicates tubular cell damage:

• Interstitial nephritis
• Analgesics nephropathy
• Chronic pyelonephritis in vesicoureteral reflux
• Acute renal failure
• Tubular toxins like aminoglycosides, contrast medium or ciclosporin.

Prerenal Proteinuria:

• Bence Jonce proteinuria in multiple myeloma or Non-Hodgkin lymphoma
• Rhabdomyolysis
• Hemolysis

Postrenal Proteinuria:

Tumor, urogenital trauma, urinary tract infections, hematuria, semen, vaginal contamination.

Diagnostic Workup of Proteinuria

• Urine sediment and urine culture
• Protein concentration in 24-hour urine collection
• Protein electrophoresis of urine and serum
• Sonography of the urinary organs: renal ultrasound and bladder ultrasound imaging.
• Intravenous urography or computed tomography of urinary organs if postrenal proteinuria is suspected.
• Immun-electrophoresis, if Bence Jones proteinuria is suspected
• Renal biopsy if severe proteinuria or signs of renal dysfunction are present.

References

  Deutsche Version: Differentialdiagnose der Proteinurie

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