EVALUATION OF ASYMPTOMATIC PROTEINURIA IN CHILDREN

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EVALUATION OF ASYMPTOMATIC PROTEINURIA IN CHILDREN

• By Patricia Baile

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MECHANISMS OF PROTEIN HANDLING BY KIDNEY

• 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

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MECHANISMS OF PROTEIN HANDLING BY KIDNEY

• 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

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MECHANISMS OF PROTEIN HANDLING BY KIDNEY

• 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

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NORMAL PROTEIN EXCRETION

• Normal protein excretion
• Child lt 100mg/m2/day or 150mg/day
• Neonates up to 300mg/m2

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ABNORMAL PROTEIN EXCRETION

• 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.

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ABNORMAL PROTEIN EXCRETION

• 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

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ABNORMAL PROTEIN EXCRETION

• 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

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ABNORMAL PROTEIN EXCRETION

• 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

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ASYMPTOMATIC PROTEINURIA

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

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MEASUREMENT OF URINARY PROTEIN

• 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 gt1000 mg/dL

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MEASUREMENT OF URINARY PROTEIN

• 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

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MEASUREMENT OF URINARY PROTEIN

• 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 gt100 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

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MEASUREMENT OF URINARY PROTEIN

• 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 gt2 yrs normal value for this ratio
  is lt0.2 mg protein/mg creatinine
• For infants and children lt2yrs lt0.5 mg
  protein/mg creatinine

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CAUSES OF ASYMPTOMATIC PROTEINURIA
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TRANSIENT PROTEINURIA

• 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

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ORTHOSTATIC 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

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PERSISTENT PROTEINURIA

• 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

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DIFFERENTIAL DIAGNOSES OF PERSISTENT PROTEINURIA

• 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

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EVALUATION OF ASYMPTOMATIC PROTEINURIA
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HISTORY

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

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HISTORY

• Swollen joints
• Abdominal pain
• Previous abnormal urinalysis
• Growth history
• Medications
• Family history
• Renal disease, hypertension, deafness, visual
  disorders

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PHYSICAL EXAMINATION

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

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LABORATORY EVALUATION
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TRANSIENT PROTEINURIA

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

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ORTHOSTATIC PROTEINURIA

• Perform Orthostatic Test
• CBC
• BUN
• Creatinine
• Electrolytes
• 24-hr urine excretion
• lt 1.5g/day ? repeat UA and blood work in 1 year
• gt 1.5g/day ? refer to Pediatric Nephrologist

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Instructions for Testing for Orthostatic
Proteinuria

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.

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FURTHER EVALUATION OF PERSISTENT PROTEINURIA

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

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OTHER TESTS

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

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PERSISTENT PROTEINURIA

• 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

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INDICATIONS FOR RENAL BIOPSY

• 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.

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MANAGEMENT

• Avoid excessive restrictions in childs 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

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REFERENCES

• UpToDate
• Feld L, Schoeneman M, Kaskel F Evaluation of the
  Child with Asymptomatic Proteinuria. Pediatrics
  in Review 1984 5 248-254
• Nelsons Textbook of Pediatrics

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QUESTIONS?