1. EVALUATION OF ASYMPTOMATIC PROTEINURIA IN CHILDREN
By: Patricia Baile

2. MECHANISMS OF PROTEIN HANDLING BY KIDNEY
Glomerular capillary wall permits passage of small molecules while restricting macromolecules

3. 3 components of glomerular wall
Endothelial cell
Basement membrane
Epithelial cell

4. 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

5. 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

6. NORMAL PROTEIN EXCRETION
Child: < 100mg/m2/day or 150mg/day
Neonates: up to 300mg/m2

7. 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.

8. 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

9. 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

10. 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

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

12. 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

13. 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

14. 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

15. 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

16. CAUSES OF ASYMPTOMATIC PROTEINURIA

17. 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

18. ORTHOSTATIC PROTEINURIA
Increase in protein excretion in the erect position compared with levels measured during recumbency
Proteinuria usually does not exceed 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. 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

20. 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

21. EVALUATION OF ASYMPTOMATIC PROTEINURIA

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

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

24. 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

25. LABORATORY EVALUATION
Single urine positive for protein
1) first morning void Pr/Cr
2) UA in office
Obtain:
Pr/Cr and UA normal
Transient Proteinuria
Pr/Cr normal, UA positive
Orthostatic Proteinuria
Both specimens abnormal
Persistent Proteinuria

26. TRANSIENT PROTEINURIA
Follow-up routinely
Patient should have a repeat urinalysis on a first morning void in one year

27. 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

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

29. 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

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

31. 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

32. 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.

33. 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

34. REFERENCES
UpToDate
Feld L, Schoeneman M, Kaskel F: Evaluation of the Child with Asymptomatic Proteinuria. Pediatrics in Review 1984; 5:
Nelson’s Textbook of Pediatrics

35. QUESTIONS?