Evaluation of proteinuria in children - by Dr.B.Sivakanth

EVALUATION OF PROTEINURIA IN CHILDREN

BY: DR.B.SIVAKANTHWARD 15ACOLOMBO SOUTH TEACING HOSPITAL

CONTENTS

• Introduction to proteinuria

•Assess the urinary protein

•Types of proteinuria

•Approach to a child with proteinuria

INTRODUCTION

• The demonstration of proteinuria on a routine screening urinalysis is common

• 10% of children aged 8-15 yr test positive for proteinuria by urinary dipstick at some time.

• The challenge is to differentiate the child with proteinuria related to renal disease from the otherwise healthy child with transient or other benign forms of proteinuria.

MECHANISMS OF PROTEIN HANDLING BY KIDNEY

• Glomerular capillary wall permits passage of small molecules while restricting macromolecules

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

MECHANISMS OF PROTEINURIA

• Nephrotic syndrome - increased permeability of the glomerular capillary wall

• On biopsy, the extensive effacement of podocyte foot processes (the hallmark of idiopathic nephrotic syndrome.

• Idiopathic nephrotic syndrome is associated with complex disturbances in the immune system, especially T cell– mediated immunity.

• focal segmental glomerulosclerosis -

• a plasma factor produced by a subset of activated lymphocytes.

• mutations in podocyte proteins (podocin, α-actinin 4) and MYH9 (podocyte gene)

• Steroid- resistant nephrotic syndrome - mutations in NPHS2 (podocin) and WT1 genes, slit pore, and include nephrin, NEPH1, and CD-2 associated protein.

MEASUREMENT OF URINARY PROTEIN

Qualitative

•Urine dipstick•Sulfosalicylic acid test

Quantitative

•timed 24-hour urine collection•measurement of the urinary protein/creatinine ratio


Urine dipstick

•Offers a qualitative assessment of urinary protein excretion.

• Primarily detect albuminuria

• less sensitive for other forms of proteinuria (low molecular weight proteins, Bence Jones protein, gamma globulins.


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



4+ — >1000 mg/dL

MEASUREMENT OF URINARY PROTEINUrine dipstick

Will not detect LMW proteins.

False positive –

Very Alkaline sample pH >7.0

contaminated by antiseptic agents

Chlorhexidine or Benzalkonium chloride

Iodinated radiocontrast agents.

Gross hematuria

False Negative –

dilute urine (specific gravity <1.005)

In which the predominant urinary protein is not albumin


• 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 with three parts 3 percent sulfosalicylic acid, followed by assessment of the degree of turbidity


Quantitative assessment •most common method - 24-hour urine collection

•Normal protein excretion

•Child: < 100mg/m2/day or 150mg/day

•Neonates: up to 300mg/m2/day

• 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


Quantitative assessment• Alternative method - measurement of the total

protein/creatinine ratio (mg/mg) on a spot urine sample,

• best performed on a first morning voided urine specimen to eliminate the possibility of orthostatic (postural) proteinuria

• normal protein excretion Ratios

•<0.5 in children <2 yr of age

•<0.2 in children ≥2 yr of age.

• A ratio >2 suggests nephrotic-range proteinuria.

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.


•Glomerular proteinuria

•Tubular proteinuria

•Transient Proteinuria

•Overflow Proteinuria

•Orthostatic Proteinuria

ABNORMAL PROTEIN EXCRETION•Glomerular proteinuria

•Due to increased filtration of macromolecules

• range from <1 g to >30 g/24 hr

•Glomerular proteinuria should be suspected in any

• patient with a first morning urine protein : creatinine ratio >1.0, or

• proteinuria of any degree, accompanied by

• hypertension, hematuria, edema, or renal dysfunction.

• Glomerular proteinuria

• Result from

• nephrotic syndrome

• Amyloidosis

• diabetic nephropathy

• acute postinfectious glomerulonephritis

• IgA nephropathy

• lupus nephritis

• Henoch-Schönlein purpura nephritis

• Alport syndrome

• Sickle cell nephropathy

• Lupus nephritis



•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

•Transient Proteinuria•Most common cause

• Usually not exceed 1-2+

• Can occur in association with

• fever >38, 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



•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

ORTHOSTATIC PROTEINURIAMost common cause for persistent proteinuria in school aged

children

Usually asymptomic

Increase in protein excretion up to 10 fold 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

ASYMPTOMATIC PROTEINURIA

•Levels of protein excretion above the upper limits of normal for age

•No clinical manifestations such as edema, hematuria, oliguria, and hypertension

PERSISTENT PROTEINURIA

• Persons found to have significant proteinuria on a first morning urine sample on 3 consecutive days

• Indicates renal disease and may be caused by either glomerular or tubular disorders.

• >1+ on dipstick with urine specific gravity >1.015 or protein : creatinine ratio >0.2

APPROACH TO THE CHILD WITH PROTEINURIA

HISTORY• Recent infection

• Weight changes

• Presence of edema

• Symptoms of hypertension

• Gross hematuria

• Changes in urine output

• Dysuria

• Skin lesionsSwollen joints

• Abdominal pain

• Previous abnormal urinalysis

• Growth history

• Medications

• Family history

• Renal disease, hypertension, deafness, visual disorders

PHYSICAL EXAMINATION• Inspect for presence of edema, pallor, skin

lesions, skeletal deformities

• Vital signs

• Abdominal exam

• Respiratory exam

• Cardiac exam

LABORATORY EVALUATION

Single urine positive for protein

Obtain:1) first morning void Pr/Cr

2) UA in 24h urine

Pr/Cr and UA normal

Transient Proteinuria

Pr/Cr normal, UA positive

Orthostatic Proteinuria

Both specimens abnormal

Persistent Proteinuria

TRANSIENT PROTEINURIA

• Follow-up routinely

• Patient should have a repeat urinalysis on a first morning void in one year



2) UA in 24h urine

Pr/Cr and UA normal


Pr/Cr normal, UA

positive




ORTHOSTATIC PROTEINURIA

• Perform Orthostatic Test

•Renal function test

• 24-hr urine excretion

• < 1.5g/day repeat UA and blood work in 1 year

• > 1.5g/day refer to Pediatric Nephrologist



2) UA in 24h urine

Pr/Cr and UA normal






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 - specimen #1.

3. Child should ambulate for the next 2 to 3 hours. Then collect specimen. - specimen #2.

4. Both specimens are tested by dipstick or sulfosalicylic acid.

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

• FBC

•Renal function tests (blood urea nitrogen and creatinine)

•Cholesterol

• Albumin and total protein



2) UA in 24h urine

Pr/Cr and UA normal






OTHER TESTS

•Renal ultrasound

• Serum complement levels (C3 and C4)

• ANA

•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

• Recommendations for renal biopsy.

1. Onset < 6 months of age

2. Initial macroscopic haematuria (without infection)

3. Persistent microscopic haematuria with hypertension

4. Renal failure not attributable to hypovolaemia

5. Persistently low plasma C3, C4 levels

6. Steroid resistance

Renal biopsy is discretionary if:

1. Onset 6-12 months of age

2. Onset above 12 years

3. Persistent hypertension, persistent microscopic haematuria in isolation

4. Frequently relapsing disease before commencing on second line drugs (especially cyclosporin A)

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

SUMMARY

• Normal protein excretion

• Child: < 100mg/m2/day or 150mg/day

• Neonates: up to 300mg/m2/day

• Proteinuria of greater than 40 mg/m2 per hour is considered heavy or in the nephrotic range• Urine dipstick – qualitative

• 24 hour urine protein, urine Pr/Cr ratio – quantitative

• Abnormal protein excretion - Glomerular proteinuria, Tubular proteinuria, Transient Proteinuria, Overflow Proteinuria, Orthostatic Proteinuria

• Orthostatic and transient protinuria are benign

• Persistent proteinuria needs further evaluation and disease specific management.

REFERENCES

• Nelson’s Textbook of Pediatrics 19th edition

• Illustrated textbook of paediatrics 4th edition

• UpToDate

• National Guidelines of Srilanka

THANK YOU

Evaluation of proteinuria in children - by Dr.B.Sivakanth

Health & Medicine

Transcript of Evaluation of proteinuria in children - by Dr.B.Sivakanth