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By: Dr. Arshad Khan PG Peads KTH
Glomerular capillary wall permits passage of small molecules while restricting macromolecules
3 components of glomerular wallEndothelial cellBasement
membranePodocyte
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.
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 excretionChild: < 100mg/m2/day or 150mg/dayNeonates: up to 300mg/m2
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.
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
Tubular proteinuriaResults 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
Overflow ProteinuriaResults from increased excretion of low
molecular weight proteins due to marked overproduction of a particular protein to a level that exceeds tubular reabsorptive capacity
Levels of protein excretion above the upper limits of normal for age
No clinical manifestations such as edema, hematuria, oliguria, and hypertension
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)
Sulfosalicylic acid testDetects 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
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 voids
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
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
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
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
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
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
Recent infection Weight changes Presence of edema Symptoms of hypertension Gross hematuria Changes in urine output Dysuria Skin lesions
Swollen joints Abdominal pain Previous abnormal urinalysis Growth history Medications
Family historyRenal disease, hypertension, deafness,
visual disorders
Vital signs Inspect for presence of edema, pallor,
skin lesions, skeletal deformities Screening for hearing and visual
abnormalities Abdominal exam Lung exam Cardiac exam
Follow-up routinely Patient should have a repeat urinalysis
on a first morning void in one year
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
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.
Examination or urine sediment CBC Renal function tests (blood urea
nitrogen and creatinine) Serum electrolytes Cholesterol Albumin and total protein
Renal ultrasound Serum complement levels (C3 and C4) ANA Streptozyme testing, Hepatitis B and C serology HIV testing
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
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.
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
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