EVALUATION OF ASYMPTOMATIC PROTEINURIA IN CHILDREN By: Patricia Baile.
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Transcript of EVALUATION OF ASYMPTOMATIC PROTEINURIA IN CHILDREN By: Patricia Baile.
EVALUATION OF ASYMPTOMATIC PROTEINURIA IN CHILDREN
By: Patricia Baile
MECHANISMS OF PROTEIN HANDLING BY KIDNEY
Glomerular capillary wall permits passage of small molecules while restricting macromolecules
3 components of glomerular wall Endothelial cell Basement
membrane Epithelial cell
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
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
NORMAL PROTEIN EXCRETION Normal protein excretion
Child: < 100mg/m2/day or 150mg/day Neonates: up to 300mg/m2
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.
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
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
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
ASYMPTOMATIC PROTEINURIA
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 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
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
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 >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 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
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 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
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 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
Recent infection Weight changes Presence of edema Symptoms of hypertension Gross hematuria Changes in urine output Dysuria Skin lesions
HISTORY
Swollen joints Abdominal pain Previous abnormal urinalysis Growth history Medications
Family history Renal disease, hypertension, deafness,
visual disorders
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
LABORATORY EVALUATION
TRANSIENT PROTEINURIA
Follow-up routinely Patient should have a repeat urinalysis
on a first morning void in one year
ORTHOSTATIC PROTEINURIA 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 Proteinuria1. 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.
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
OTHER TESTS
Renal ultrasound Serum complement levels (C3 and C4) ANA Streptozyme testing, Hepatitis B and C serology HIV testing
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
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.
MANAGEMENT
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
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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