PROTEINURIA
DEFINITION:
The excretion of an excessive amount of protein (>150mg/day) in
the urine as defined by qualitative, semiquantitative, and
quantitative methods.
EPIDEMIOLOGY:
- incidence: 1 - 5% (depend upon age and number of samples)
- prevalence: 5 - 11% (1+ proteinuria)
- only 10% of kids with proteinuria will have abnormalities
after 6-10 month of follow-up
- of those children with isolated proteinuria, <2% will have
significant underlying renal disease
- the incidence of proteinuria in patients with underlying renal
disease is remarkably high
DIFFERENTIAL DIAGNOSIS:
PATHOGENESIS:
- mechanisms:
- proteins: larger macromolecules, albumin
2. Tubulointerstitial
- impaired tubular reabsorption of filtered proteins
- proteins: low MW proteins, lysozyme, B2-microglobulin,
- Tamm-Horstall protein
3. Overload Proteinuria
- increased load overloads tubular reabsorptive capacity
- proteins: low MW plasma proteins, Ig light chains,
myoglobulin, lysozyme, albumin
CLINICAL FEATURES:
- at the end of the history, one should be able to discern:
- onset
- when began with conditions identified around the initial
presentation, i.e., drug ingestion
- record of previous urinalyses
- precipitation/palliation
- identification of triggering agents
- infectious, drugs, foods, chemicals, vaccinations
- helps to identify acquired forms of tubulointerstitial
proteinuria
- quality
- associated with hematuria
- severity
- more likely to be pathologic proteinuria if associated
with hematuria or Nephrotic Syndrome (edema, hypoalbuminemia,
hypercholesterolemia)
- if Nephrotic Syndrome present:
- likely to be a primary GN
- unlikely to be benign etiology or secondary GN
- timing
- acute vs acute-on-chronic
- intermittent vs persistent
- duration of proteinuria
- associated symptoms
- past medical history
- functional inquiry
- see Specific Entities below and files in the Database on
the individual disorders listed in the differential
diagnosis of proteinuria
- helps to differentiate acute GN from chronic GN
- helps to identify overload proteinuria causes
2. Family History
- helps to differentiate hereditary from non-hereditary forms
of both glomerular and tubulointerstitial forms of proteinuria:
- family members must have had previous urinalysis to
ascertain this
2. Renal Disease
- Polycystic Kidney Disease
- Nephrotic Syndrome, Fanconi Disease
- renal dialysis
- kidney transplantation
3. Others
- hearing/ocular impairment (Alport Syndrome)
3. Physical Examination
4. Specific Entities
- benign proteinuria associated with precipitating factors -
fever, exercise, stress, cold weather, dehydration, high blood
pressure, seizures, etc
2. Orthostatic Proteinuria
- diagnosis based upon the Postural Test
- has a benign clinical course
3. Persistent Asymptomatic Proteinuria
- proteinuria that persists for 3-6 months
- renal biopsy after 6 months of persistent proteinuria and
if FSGS then at risk for chronic renal failure
4. Congenital Nephrotic Syndrome
- onset at birth with Nephrotic Syndrome (massive
proteinuria, hypoalbuminemia, edema, and hyperlipidemia)
- very difficult to treat with poor prognosis
5. Poststreptococcal GN
- proteinuria + hematuria
- associated symptoms
- prodrome of pharyngitis, URTI, impetigo
- Nephrotic and/or Nephritic Syndrome
6. Hemolytic Uremic Syndrome
- proteinuria + hematuria
- associated symptoms
- prodrome of bloody diarrhea
- anemia and thrombocytopenia (petechiae)
- Nephrotic and/or Nephritic Syndrome
7. Henoch-Schoenlein Purpura
- proteinuria + hematuria
- associated symptoms
- purpuric rash, arthritis, abdominal pain
- Nephrotic and/or Nephritic Syndrome
8. Primary Glomerulonephritis
- isolated proteinuria +/- Nephrotic Syndrome
- associated symptoms
- edema, hypoalbuminemia, hyperlipidemia
- see file on "Idiopathic Nephrotic Syndrome"
9. Secondary Glomerulonephritis
- proteinuria +/- hematuria associated with a disease
entity, i.e., SLE, Goodpastures Disease, Wegeners Disease,
Diabetes Mellitus
10. Hereditary Tubulointerstitial Proteinurias
- tubular proteinuria
- associated symptoms
- episodes of vomiting, dehydration, weakness, fever,
anorexia, constipation, failure to thrive, polydipsia,
polyuria
- see file on "Fanconi Syndrome"
INVESTIGATIONS:
- measures a range of protein concentrations
- depth of colour increases in a semiquantitative manner
with increasing urinary protein concentration
- to rule out false positives must have:
- 3 samples with proteinuria
- first voided early morning samples
- pH < 6.0 with known specific gravity
- 1+ (72-240 mg/24 hrs) or greater is considered abnormal
- dependent on specific gravity of urine sample
- FP: elevated sg., gross hematuria, highly alkaline urine,
UTI
2. Semi-quantitative - Protein/Creatinine Ratio in Urine
- random early morning single voided specimen
- children < 2 years : < 0.5
- children > 2 years : < 0.2
- nephrotic : > 3.5
- correlates with the 24 hour protein excretion data
3. Quantitative - 24 hr. urine collection
- gold standard
- if dipstick is 1+ or more than obliged to do a 24 hour
urine collection
- 24 hr. urine collection
- Protein (mg)/m2/hr
- < 4 mg/m2/hour (normal)
- 4-40mg/m2/hour (proteinuria)
- 40 mg/m2/hour (nephrotic)
- Protein (mg)/24 hr
- 2 to 12 months : > 155 mg/24 hr
- 3 to 4 years : > 140 mg/24 hr
- 4 to 10 years : > 190 mg/24 hr
- 10 to 16 years : > 250 mg/24 hr
- FP: radiographic contrast media, cephalosporins, pencillin
analogues, sulfonamide metabolites
2. Indications for Further Investigation
- Non-orthostatic Proteinuria
- Persistent Proteinuria
- Symptomatic (edema, elevated BP, abdominal pain, hematuria)
3. First Line Investigations
- R&M, C&S, microscopy
- orthostatic test
- 24 hour collection
- total protein
- creatinine clearance
2. Serum
- electrolytes, BUN, creatinine, albumin, cholesterol,
triglyceride, calcium, protein, CBC
- orthostatic test
4. Second Line Investigations
- protein electrophoresis can be used to differentiate
glomerular (albumin) from tubular (Tamm-Horstall) proteinuria
2. Serum
- IgA, PTH, ANA, protein electrophoresis, ASOT, anti-GBM
antibodies, uric acid, C3, C4
3. Imaging Studies
- renal ultrasound to rule out renal vein thrombosis
4. Renal Biopsy
- indicated for:
- progressive proteinuria with hematuria
- all forms of Nephrotic Syndrome except that caused by
steroid-responsive Minimal Change Disease
MANAGEMENT:
- treat underlying disorder
- treat complications
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