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