Proteins filtered by the glomerulus are usually reabsorbed almost completely such that no significantly detectable amounts are found in urine. But in some pathological conditions, proteins appear in urine either as microalbuminuria or frank proteinuria. This presentation discusses the different types of proteinuria and some conditions that can lead to them.
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Proteinuria Causes and Tests
1. Department of Chemical Pathology,
Federal Teaching Hospital Abakaliki
Clinical Presentation on:
Proteinuria
By: Dr Onu Emmanuel Mbah
Date: 11 Feb. 2016
Supervising Consultant: Dr Okeke NJ
2. Outline
• Introduction
• Classification of proteinuria
• Testing for proteinuria
• Limitation of screening tests
• Investigating a patient with proteinuria
• Appreciation
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3. Introduction
• Proteinuria is defined as the presence of
excessive proteins in the urine.
• Normal urinary protein excretion is < 150 mg/24
hour, mostly alb. and then Tamm-Horsfall protein
• Daily albumin excretion in a normal person is < 30
mg.
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4. .
• UAER averages 2.6-12.6 µg/min in males and 1.1-
21.9 µg/min in females.
• Microalbuminuria is referred to as the excretion of
30-300 mg of albumin daily or 20-200 µg of
albumin per minute.
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5. .
• The glomerular basement membrane (GBM) acts
as an ultrafilter for plasma proteins
• The ability of individual proteins to pass through
the membrane is a function of:
• (1) molecular size
• (2) net ionic charge
• (3) plasma concentration of the proteins.
• Transport of protein molecules through the
glomerular membrane is inversely related to size
and net negative charge.
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6. .
• Significant amount of Albumin (64 kDa) is passed
into the filtrate as a result of its high plasma
concentration and relatively low molecular mass.
• Proteins with molecular masses of 15 to 40
kDa filter more readily but in lesser quantities
because of their low plasma concentrations.
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8. Tubular Proteinuria
• Tubular proteinuria occurs most commonly in
tubulo-interstitial diseases of the kidney
• It comprises low molecular proteins such as beta-2
microglobulin, which in normal conditions are
completely reabsorbed by proximal tubules.
• The amount of proteinuria is < 2 g and dipstick may
be negative.
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9. .
• Agarose electrophoresis of urine gives a
characteristic pattern-prominent a- and P-bands,
a relatively faint albumin band, and sometimes
a post-yband.
• Sodium dodecyl sulfate polyacrylamide gel
electrophoresis (SDS-PAGE) is more useful in
detecting tubular proteinuria in the presence of
glomerular proteinuria as it separates proteins by
molecular size.
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10. .
• Acute tubular proteinuria complely reversible
• May occur in:
• (1) burns,
• (2) acute pancreatitis,
• (3) heavy metal poisoning,
• (4) administration of renotoxic drugs
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11. .
• Chronic tubular proteinuria is usually irreversible, may
be severe
• Causes:
• Hereditary, as in Fanconi syndrome
• Acquired:- localized dz e.g chronic pyelonephritis -
systemic disease, e.gs cirrhosis, sarcoidosis.
• drugs, e.g phenacetin
• toxins e.g cadmium
• Diminished or diminishing tubular reabsorption is
suggested by increasing concentrations of low
molecular mass proteins in urine.
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12. Glomerular Proteinuria
• This is the most common and serious type of
proteinuria.
• Patients are routinely screened for this disorder
by a simple diptick test for albumin.
• If the dipstick test result is negative, clinically
significant glomerular proteinuria is precluded.
• Because most of the excreted protein is albumin,
glomerular proteinuria is often termed albuminuria
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13. Classification of Glomerular
Proteinuria
• Pathological
• Nephrotic/overt
• Non-nephrotic
• Functional/benign
• Transient proteinuria
• Orthostatic proteinuria
• Functional proteinuria is seen in (1) exercise, (2)
pyrexia, (3) exposure to cold, (4) congestive heart
failure, (5) hyperten- sion, and (6) arteriosclerosis.
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14. Transient Proteinuria
• Occurs in patients with normal renal function, bland
urine sediment, and normal BP
• The quantitative protein excretion is less than 1 g/day.
• The proteinuria is not indicative of significant
underlying renal disease
• It may be precipitated by high fever or heavy exercise
• It disappears upon repeat testing.
• In normal pregnancy, protein excretion may increase
harmlessly to 200 to 300 mg/d.
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15. Orthostatic Proteinuria
• Postural or orthostatic proteinuria is associated
with the upright position
• Here the patient has no proteinuria in early morning
samples but has low-grade proteinuria at the end of
the day.
• It usually occurs in tall, thin adolescents or adults
younger than 30 years (and may be associated with
severe lordosis).
• Patients have normal renal function and proteinuria
usually is less than 1 g/day with no hematuria
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16. .
• In non-nephrotic proteinuria, the amount of
proteinuria is < 3.5 g/24 h and is persistent
• It can occur in preeclampsia
• Nephrotic-range proteinuria is defined as >3.5 g of
proteinuria on a spot urine protein–to-creatinine
ratio and denotes significant glomerular disease
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17. Overflow Proteinuria
• Occurs when proteins are produced in amounts
greater than the reabsorptive capacity of the
proximal tubule.
• It includes (1) hemoglobinuria, (2)myoglobinuria,
and (3) Bence Jones proteinuria
• These low molecular proteins can be toxic to the
tubules and can cause acute kidney injury.
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18. Testing for Urinary Protein
• Fresh sample should be used
• Screening test involves dipstick test e.g with
albustix (with tetrabromophenol blue)
• Albustix is buffered to PH 3; normally yellow
• It turns green or bluish-green if protein is
present.
• The colour is then matched on a chat to indicate
the protein conc.
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19. Limitations of Screening Tests
• The tests were mainly developed to detect albumin
and may be negative in the presence of other
proteins, such as BJP.
• Because the tests depend on protein
concentrations, very dilute urine may give negative
results despite significant proteinuria.
• False-negative results occur if acid has been
added to the urine as a preservative
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20. .
• False-positive results occur:
• if the specimen is contaminated with vaginal or
urethral secretions, including haematuria, semen or
menstrual fluid,
• in strongly alkaline (infected or stale) urine, when
buffering capacity is exceeded; a green colour in this
case is a reflection of the alkaline pH,
• if the urine container is contaminated with
disinfectants such as chlorhexidine.
• Spot urine ACR or P:C ratio (in pregnancy) is more
convenient. (P:C in mg/mmol; ACR in g/d)
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22. Treatment
• Nonspecific treatment - Treatment that is
applicable irrespective of the underlying cause.
• Specific treatment - Treatment that depends on the
underlying renal or nonrenal cause
• The patient is referred to a nephrologiste esp. if
bad prognostic indecis are observed eg albuminuria
> 1g/d, or worsening renal funxn
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23. • Use of ACEIs or ARBs
• Target blood pressure is less than 125/75 mm Hg.
• The dose of ACE inhibitor should be increased as
tolerated until this blood pressure is achieved.
• Normotensive patients with proteinuria also should
be given ACEIs.
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24. • Diuretics
• Patients with moderate to severe proteinuria are
usually fluid overloaded and require diuretic
therapy along with dietary salt restriction.
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