ppt

1. By: Dr. Arshad Khan PG Peads KTH

2.  Glomerular capillary
wall permits passage
of small molecules
while restricting
macromolecules

3.  3 components of
glomerular wall
Endothelial cell
Basement membrane
Podocyte

4.  Glomerular permeability
 The charge and size selective properties of the
glomerular capillary wall prevent significant
amounts of albumin, globulin, and other large
plasma proteins from entering the urinary space
 LMW protein do cross the capillary wall but are
reabsorbed by the proximal tubule.
 small amount o f protein that normally appears
in the urine is the result of normal tubular
secretion.

5.  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

6.  Normal protein excretion
 Child: < 100mg/m2/day or 150mg/day
 Neonates: up to 300mg/m2

7.  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.

8. 3 possible mechanisms
 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

9.  Tubular proteinuria
 Results from increased excretion of low
molecular weight proteins such as beta-2-
microglobulin, alpha-1-microglobulin, and
retinol-binding protein
 Tubulointerstitial diseases, can lead to increased
excretion of these smaller proteins

10.  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

11.  Levels of protein excretion above the upper
limits of normal for age
 No clinical manifestations such as edema,
hematuria, oliguria, and hypertension

12.  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
 False positive results: Urine pH(>7.0), concentrated
urine (SG >1.025)
 Contamination of the urine with blood
 Positive Urine dipstick test for protein (>trace 10-29
mg/dl)

13.  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

14.  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/day (or 4
mg/m2 /hour) are abnormal
 Proteinuria of greater than 40 mg/m2/hour is
considered heavy or in the nephrotic range
 Drawbacks: difficult to obtain
influenced by fluid intake, the
volume of urine output, and the
importance of including a complete
collection without missed

15.  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 (to eliminate the
possibility of orthostatic portienuria)
 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
 Ratio > 2 suggests nephrotic range proteinuria

17.  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
 Usually does not exceed 1-2+ on dipstick
 Benign condition (No evaluation or therapy is
needed

18.  Most common cause (60%) of persistent
proteinuria
 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

19.  In children with persistent asymptomatic
praterinuria, initial evaluation should inclucd
assessment for orthostatic proteunuria
 Absence of proteinuria (dipstack negative or
trace for protein and a normal ratio of
urinary protein: creatinine<0.2) on the first
morning urine sample for 3 consecutive days
confirms the diagnosis of orthostatic
proteinuria
 No further is necessary
 Reassurance of the patient and family

20.  Defined as a first morning urine sample ≥1+
on dipstick testing with a urine SG >1.015 or
with protein: creatinine ratio of ≥0.2
 Indicate: poteninoal kidney disease caused
by either.
Glomerular or tubular disorders

21.  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

23.  Recent infection
 Weight changes
 Presence of edema
 Symptoms of hypertension
 Gross hematuria
 Changes in urine output
 Dysuria
 Skin lesions

24.  Swollen joints
 Abdominal pain
 Previous abnormal urinalysis
 Growth history
 Medications
 Family history
 Renal disease, hypertension, deafness, visual
disorders

25.  Vital signs
 Inspect for presence of edema, pallor, skin
lesions, skeletal deformities
 Screening for hearing and visual
abnormalities
 Abdominal exam
 Lung exam
 Cardiac exam

27.  Follow-up routinely
 Patient should have a repeat urinalysis on a
first morning void in one year

28.  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

29. 1. Patient voids at bedtime. Discard urine. No food or
fluids after dinner until the next morning.
2. When patient awakes in the morning, urine specimen is
collected prior to arising, or after as little ambulation as
possible. Label specimen #1.
3. Child should ambulate for the next 2 to 3 hours. Then
collect specimen. Label specimen #2.
4. Both specimens should be tested by dipstick or
sulfosalicylic acid. Specimen #1 should be concentrated
with a specific gravity of at least 1.018.
5. If specimen #1 is free of protein and specimen #2 has
protein, then the test is positive for orthostatic
proteinuria.
6. If both specimens have protein, orthostatic proteinuria
is unlikely and further evaluation is necessary.
7. This protocol should be repeated on at least 2 occasions
to confirm the diagnosis.

30.  Examination or urine sediment
 CBC
 Renal function tests (blood urea nitrogen and
creatinine)
 Serum electrolytes
 Cholesterol
 Albumin and total protein

31.  Renal ultrasound
 Serum complement levels (C3 and C4)
 ANA
 Streptozyme testing,
 Hepatitis B and C serology
 HIV testing

32.  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

33.  Many nephrologists recommend close
monitoring for those children with urinary
protein excretion below 500 mg/m2/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.

34.  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

35.  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