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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.
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References
Deutsche Version: Differentialdiagnose der Proteinurie