URINARY PROTEINS

Question 1

What is proteinuria?
The degree to which individual proteins pass through the membrane depends on what?
How much protein is present in normal urine?

Answer 1

Proteinuria is defined as an increase in the amount of protein in the urine.
The glomerular basement membrane acts as an ultrafilter for plasma proteins. The degree to which individual proteins pass through the membrane depends on:
1. Molecular size
2. Net ionic charge
3. Plasma concentration
4. Reabsorption by the renal tubules
Only a small amount of protein (20-150mg/day) mostly albumin is present in normal urine

Alteration of any of the above factors may result in proteinuria.

Question 2

What are TYPES OF PROTEINURIA?

Answer 2

1. GLOMERULAR PROTEINURIA:
   * Is the most common and serious type.
   * Usually secondary to increase in glomerular permeability.
   * The most common protein in this type is albumin
   * Example is nephrotic syndrome.
2. TUBULAR PROTEINURIA
   * Characterized by the appearance of low molecular mass proteins (usually globulins) in the urine.
   * It is due to defective reabsorption by the proximal renal tubules.
   *Markers include LMW α-globulins and β-globulins, examples are retinol-binding protein, N-acetyl- β -D-glucosaminidase, α1-macroglobulin.
   * It is also seen in Fanconi syndrome
3. OVERFLOW/OVERLOAD PROTEINURIA
   * This occurs when proteins of low molecular proteins are produced in amounts greater than the reabsorptive capacity of the renal tubule.
   * It is filtered normally by the glomerulus and also reabsorbed by the tubule. Seen in BJP (ben jones protein), haemoglobinuria, myoglobinuria
4. POSTRENAL PROTEINURIA
   Refers to proteins arising from urinary tracts below the kidneys and is usually seen in inflammation, bleeding or malignancy.
   Diagnosed by microscopic evidence of inflammation, blood, malignant cells
5. TRANSIENT PROTEINURIA
   Usually seen in physical exercise, trauma, fever. Appearance is transient.
6. ORTHOSTATIC (POSTURAL) PROTEINURIA
   Associated with and more severe in upright standing than in prone position.

Question 3

What is microalbuminuria/ paucialbuminuria?

Answer 3

Normoalbuminuria <30mg/day OR <20µg/min
Albumin: Creatinine ratio (ACR) <2.5 mg/mmol–Male
<3.5 mg/mmol -Female

Microalbuminuria urinary albumin excretion (UAE) of 30-300 mg/day
OR 20-200 µg/min

 UAC				20-300 mg/l
UAER			20-200µg/min (timed overnight collection)
					    30-300 mg/mmol   Albumin: Creatinine ratio (ACR)  2.5-25 mg/mmol 
					                                 30-300 mg/g

Question 4

Classification of Clinical nephropathy

Answer 4

Urinary albumin concentration (UAC) >300mg/l (30mg/dl)
Urinary albumin excretion rate (UAER) >300mg/24 hr
Urinary albumin excretion >500mg/24 hr

Question 5

Classication of proteinuria based on severity

Answer 5

1. Mild Proteinuria
   24-hour urine protein: 150–500 mg/day
   Spot UPCR: 0.15–0.5 g/g (15–50 mg/mmol)
   May suggest early kidney dx, transient condition, fever, exercise
2. Moderate Proteinuria
   24-hour urine protein: 500–3,500 mg/day
   Spot UPCR: 0.5–3.5 g/g (50–350 mg/mmol)
   Indicates significant kidney disease eg nephritis or early stages of nephrotic syndrome.
3. Severe Proteinuria
   24-hour urine protein: >3,500 mg/day (3.5 g/day)
   Spot UPCR: >3.5 g/g (>350 mg/mmol)
   Diagnostic for nephrotic-range proteinuria, commonly associated with nephrotic syndrome.

Question 5

• Investigations of proteinuria

Answer 5

Normal Urinary Total Proteins- 30-150mg/day
IMPORTANT
Ensure urine sample is fresh
Most screening tests were developed to detect mainly albumin. May be negative in the presence of other proteins eg BJP
Dilute urine may also give false negative results
Exclude urinary tract infections: Midstream urine is very helpful
Plasma PSA assessment for men to rule out prostatic disease
* Routine urinalysis for proteins (Qualitative and Quantitative)
* Renal Function Tests: Plasma Urea, Creatinine, Albumin and Total Proteins
* A 24-hour Total proteins or Random Urine Albumin:creatinine ratio
* Bence Jones Protein (BJP)
* Urine Electrophoresis. Using Agarose gel or cellulose acetate gives similar result as serum electrophoresis. Concentrated urine is however required. Otherwise more sensitive staining method (eg Gold or Silver) stains would be needed
* Turbidimetry
* Biuret methods