Transcript EVALUATION OF PROTEINURIA IN CHILDREN

EVALUATION OF
ASYMPTOMATIC PROTEINURIA
IN CHILDREN
By: Patricia Baile
MECHANISMS OF PROTEIN
HANDLING BY KIDNEY
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Glomerular capillary
wall permits passage
of small molecules
while restricting
macromolecules
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3 components of
glomerular wall
 Endothelial
cell
 Basement membrane
 Epithelial cell
MECHANISMS OF PROTEIN
HANDLING BY KIDNEY
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Glomerular permeability
 Steric
hindrance: due to spatial alignment of the
passing molecules, relative to membrane pores
 Viscous drag: impedance to movement caused by fluid
lining the pores
 Electrical hindrance: due to electrostatic repulsion
between epithelial surface and plasma proteins
MECHANISMS OF PROTEIN
HANDLING BY KIDNEY
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Normal protein excretion affected by interplay of
glomerular and tubular mechanisms
Glomerular injury: abnormal losses of intermediate
MW proteins like albumin
Tubular damage: increased losses of low MW
proteins
NORMAL PROTEIN EXCRETION
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Normal protein excretion
 Child:
< 100mg/m2/day or 150mg/day
 Neonates: up to 300mg/m2
ABNORMAL PROTEIN EXCRETION
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Urinary protein excretion in excess of 100 mg/m2
per day or 4 mg/m2 per hour
Nephrotic range proteinuria (heavy proteinuria) is
defined as ≥ 1000 mg/m2 per day or 40 mg/m2
per hour.
ABNORMAL PROTEIN EXCRETION
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Glomerular proteinuria
 Due
to increased filtration of macromolecules
 May result from glomerular disease (most often minimal
change disease) or from nonpathologic conditions such
as fever, intensive exercise, and orthostatic (or postural)
proteinuria
ABNORMAL PROTEIN EXCRETION
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Tubular proteinuria
 Results
from increased excretion of low molecular
weight proteins such as beta-2-microglobulin, alpha-1microglobulin, and retinol-binding protein
 Tubulointerstitial diseases, can lead to increased
excretion of these smaller proteins
ABNORMAL PROTEIN EXCRETION
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Overflow Proteinuria
 Results
from increased excretion of low molecular
weight proteins due to marked overproduction of a
particular protein to a level that exceeds tubular
reabsorptive capacity
ASYMPTOMATIC PROTEINURIA
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Levels of protein excretion above the upper limits of
normal for age
No clinical manifestations such as edema,
hematuria, oliguria, and hypertension
MEASUREMENT OF URINARY PROTEIN
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Urine dipstick
Measures albumin concentration via a colorimetric reaction
between albumin and tetrabromophenol blue producing
different shades of green according to the concentration of
albumin in the sample
 Negative
 Trace — between 15 and 30 mg/dL
 1+ — between 30 and 100 mg/dL
 2+ — between 100 and 300 mg/dL
 3+ — between 300 and 1000 mg/dL
 4+ — >1000 mg/dL
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MEASUREMENT OF URINARY PROTEIN
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Sulfosalicylic acid test
 Detects
all proteins in the urine including the low
molecular weight proteins that are not detected by the
dipstick
 Performed by mixing one part urine supernatant (eg,
2.5 mL) with three parts 3 percent sulfosalicylic acid,
followed by assessment of the degree of turbidity
MEASUREMENT OF URINARY PROTEIN
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Quantitative assessment
 Children
with persistent dipstick-positive proteinuria
must undergo a quantitative measurement of protein
excretion, most commonly on a timed 24-hour urine
collection
 In children: levels >100 mg/m2 per day (or 4 mg/m2
per hour) are abnormal
 Proteinuria of greater than 40 mg/m2 per hour is
considered heavy or in the nephrotic range
MEASUREMENT OF URINARY PROTEIN
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Quantitative assessment
 Alternative
method of quantitative assessment is
measurement of the total protein/creatinine ratio
(mg/mg) on a spot urine sample, preferably the first
morning specimen
 For children >2 yrs: normal value for this ratio is <0.2
mg protein/mg creatinine
 For infants and children <2yrs: <0.5 mg protein/mg
creatinine
CAUSES OF ASYMPTOMATIC
PROTEINURIA
TRANSIENT PROTEINURIA
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Most common cause
Can occur in association with fever, seizures,
strenuous exercise, emotional stress, hypovolemia,
extreme cold, epinephrine administration,
abdominal surgery, or congestive heart failure
Believed to be glomerular in origin, related to
hemodynamic changes (decreased renal plasma
flow) rather than altered permeability of capillary
wall
ORTHOSTATIC PROTEINURIA
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Increase in protein excretion in the erect position
compared with levels measured during recumbency
Proteinuria usually does not exceed 1-1.5 gm/day
Mechanism postulated to involve an increased
permeability of the glomerular capillary wall and a
decrease in renal plasma flow
Long-term studies have documented the benign
nature of this condition, with recorded normal renal
function up to 50 years later
PERSISTENT PROTEINURIA
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Present for long periods after initial detection
Absence of both orthostatic proteinuria and clinical
evidence of renal disease
Clinical course may be benign
May be secondary to parenchymal disease
DIFFERENTIAL DIAGNOSES OF
PERSISTENT PROTEINURIA
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Benign proteinuria
Acute Glomerulonephritis, mild
Chronic Glomerular Disease that can lead to
nephrotic syndrome
Chronic nonspecific glomerulonephritis
Chronic interstitial nephritis
Congenital and acquired structural abnormalities of
urinary tract
EVALUATION OF ASYMPTOMATIC
PROTEINURIA
HISTORY
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Recent infection
Weight changes
Presence of edema
Symptoms of hypertension
Gross hematuria
Changes in urine output
Dysuria
Skin lesions
HISTORY
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Swollen joints
Abdominal pain
Previous abnormal urinalysis
Growth history
Medications
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Family history
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 Renal
disease, hypertension, deafness, visual disorders
PHYSICAL EXAMINATION
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Vital signs
Inspect for presence of edema, pallor, skin lesions,
skeletal deformities
Screening for hearing and visual abnormalities
Abdominal exam
Lung exam
Cardiac exam
LABORATORY EVALUATION
Single urine
positive for
protein
Obtain:
1) first morning void Pr/Cr
2) UA in office
Pr/Cr and UA
normal
Pr/Cr normal,
UA positive
Both specimens
abnormal
Transient
Proteinuria
Orthostatic
Proteinuria
Persistent
Proteinuria
TRANSIENT PROTEINURIA
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Follow-up routinely
Patient should have a repeat urinalysis on a first
morning void in one year
ORTHOSTATIC PROTEINURIA
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Perform Orthostatic Test
CBC
BUN
Creatinine
Electrolytes
24-hr urine excretion
1.5g/day  repeat UA and blood work in 1 year
 > 1.5g/day  refer to Pediatric Nephrologist
<
Instructions for Testing for Orthostatic
Proteinuria
1.
2.
3.
4.
5.
6.
7.
Patient voids at bedtime. Discard urine. No food or fluids after dinner
until the next morning.
When patient awakes in the morning, urine specimen is collected prior to
arising, or after as little ambulation as possible. Label specimen #1.
Child should ambulate for the next 2 to 3 hours. Then collect specimen.
Label specimen #2.
Both specimens should be tested by dipstick or sulfosalicylic acid.
Specimen #1 should be concentrated with a specific gravity of at least
1.018.
If specimen #1 is free of protein and specimen #2 has protein, then the
test is positive for orthostatic proteinuria.
If both specimens have protein, orthostatic proteinuria is unlikely and
further evaluation is necessary.
This protocol should be repeated on at least 2 occasions to confirm the
diagnosis.
FURTHER EVALUATION OF PERSISTENT
PROTEINURIA
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Examination or urine sediment
CBC
Renal function tests (blood urea nitrogen and
creatinine)
Serum electrolytes
Cholesterol
Albumin and total protein
OTHER TESTS
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Renal ultrasound
Serum complement levels (C3 and C4)
ANA
Streptozyme testing,
Hepatitis B and C serology
HIV testing
PERSISTENT PROTEINURIA
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If further work-up normal, urine dipstick should be
repeated on at least two additional specimens. If
these subsequent tests are negative for protein, the
diagnosis is transient proteinuria.
If the proteinuria persists or if any of the studies are
abnormal, the patient should be referred to a
pediatric nephrologist
Urinary protein excretion should be quantified by a
timed collection
INDICATIONS FOR RENAL BIOPSY
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Many nephrologists recommend close monitoring for
those children with urinary protein excretion below
500 mg/m2 per day before considering a biopsy
Monitoring should include assessment of blood
pressure, protein excretion, and renal function. If
any of these parameters shows evidence of
progressive disease, a renal biopsy should be
performed to establish a diagnosis.
MANAGEMENT
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Avoid excessive restrictions in child’s lifestyle
Dietary protein supplementation is of no benefit
Salt restriction unnecessary and potentially
dangerous
No indication for limitation of activity
Importance of compliance with regular follow-up
should be stressed
REFERENCES
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UpToDate
Feld L, Schoeneman M, Kaskel F: Evaluation of the
Child with Asymptomatic Proteinuria. Pediatrics in
Review 1984; 5: 248-254
Nelson’s Textbook of Pediatrics
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