introduction to a child with proteinuria

Introduction to the Introduction to the Child with Proteinuria Child with Proteinuria

Prof. Dr. Prof. Dr. Saad S Al AniSaad S Al Ani

Senior Pediatric Senior Pediatric consultantconsultant

Head of Pediatric Head of Pediatric DepartmentDepartmentKhorfakkan Khorfakkan

hospital hospital Sharjah ,UAESharjah ,UAE

[email protected]

IntroductionIntroduction

""The demonstration of proteinuria on a routine The demonstration of proteinuria on a routine screening urinalysis is screening urinalysis is commoncommon " "

"" Protein can be found in the urine of healthy Protein can be found in the urine of healthy children , with a reasonable children , with a reasonable upper limit upper limit being being

150mg/24hr 150mg/24hr ((4 mg/m2/hr4 mg/m2/hr) ) ""

1. http://www.aafp.org/afp/2010/0915/p645.html2. http://emedicine.medscape.com/article/984289

-overview#a30

Cont.Cont.

""10%10% of children aged 8-15 yr test of children aged 8-15 yr test positivepositive for for proteinuria by proteinuria by urinary dipstick urinary dipstick at some timeat some time " "

" " In a 24-hour urine collection: In a 24-hour urine collection:

NormalNormal values : values : <4 mg of protein/m2/hr <4 mg of protein/m2/hr

SignificantSignificant values : values : 4–40 mg/m2/hr4–40 mg/m2/hr

NephroticNephrotic range: range: >40 mg/m2/hr >40 mg/m2/hr ""

http://brightfutures.aap.org/3rd_edition_guidelines_and_pocket_guide.html

Cont.Cont.

" " Assess completeness of 24-hour collection Assess completeness of 24-hour collection by simultaneously measuring by simultaneously measuring urine urine

creatinine creatinine : : ≥15 mg/kg body weight ≥15 mg/kg body weight in in

a a 24-hour collection24-hour collection""

" " The challenge is to differentiate the child The challenge is to differentiate the child with with proteinuria related to renal disease proteinuria related to renal disease from from the otherwise the otherwise healthy child with transient healthy child with transient oror

other other benign forms of proteinuria benign forms of proteinuria ""

Urinary dipstick testUrinary dipstick test

" " DipsticksDipsticks primarily detect primarily detect albuminuriaalbuminuria and are and are less sensitive for other less sensitive for other forms of forms of

proteinuria:proteinuria: - low molecular weight proteins- low molecular weight proteins

- Bence Jones protein- Bence Jones protein - gamma globulins - gamma globulins ""

" " The The urinary dipstick test urinary dipstick test offers a qualitative offers a qualitative assessment of urinary protein excretionassessment of urinary protein excretion""

http://www.fpnotebook.com/Urology/Peds/PrtnrInChldrn.htm

The dipstick is reported asThe dipstick is reported as: : NegativeNegative 22) : + ) : + 100100 mg/dlmg/dl((

Trace :(10 – 20 mg/dl)Trace :(10 – 20 mg/dl) 33) : +) : +300300 mg/dlmg/dl((

11) : +) : +3030 mg/dlmg/dl(( 44) :+ ) :+ 10001000- - 20002000 mg/dlmg/dl((

Cont.Cont.

http://www.hopkinschildrens.org/proteinuria.aspx

Cont.Cont.

" " False-negative test False-negative test results can occur with:results can occur with: 1. Dilute urine (specific gravity <1.005) 1. Dilute urine (specific gravity <1.005)

2. Disease states in which the predominant2. Disease states in which the predominant urinary protein is not albuminurinary protein is not albumin""


Cont.Cont.

" " False-positive test False-positive test results may be seen with results may be seen with 11.Gross hematuria.Gross hematuria

2. Contamination with 2. Contamination with antiseptic agentsantiseptic agents i. Chlorhexidinei. Chlorhexidine

ii. Benzalkonium chlorideii. Benzalkonium chloride iii. Hydrogen peroxide iii. Hydrogen peroxide

33.Urinary pH >7.0.Urinary pH >7.0 44.Phenazopyridine therapy.Phenazopyridine therapy""


" " Because the dipstick reaction Because the dipstick reaction offers only offers only a qualitative measurement a qualitative measurement of urinary of urinary

protein excretion, children with protein excretion, children with persistent proteinuria persistent proteinuria should have should have

proteinuria quantitatedproteinuria quantitated with the more with the more precise precise spot urine protein: creatinine spot urine protein: creatinine

ratio (UPr : UCr)ratio (UPr : UCr) " "

Cont.Cont.

" " This This ratioratio is is calculated by dividingcalculated by dividing the the UPr (mg/dL) concentration by the UCr UPr (mg/dL) concentration by the UCr

(mg/dL) concentration (mg/dL) concentration and is best and is best performed on a performed on a first morning voided urine first morning voided urine

specimen specimen to eliminate the possibility of to eliminate the possibility of orthostatic (postural) proteinuriaorthostatic (postural) proteinuria " "

Cont.Cont.

" " Ratios :Ratios :

<0.5 <0.5 in children <2 yr of age in children <2 yr of age

<0.2 <0.2 in children ≥2 yr of age in children ≥2 yr of age

suggest suggest normal protein excretion.normal protein excretion. " "

Cont.Cont.

" " A ratio A ratio >2>2 suggests suggests nephrotic-range proteinuria. nephrotic-range proteinuria. ""

" " UPr : UCr ratios UPr : UCr ratios have been shown have been shown to have a to have a high correlation with high correlation with

protein excretion determinationsprotein excretion determinations in in timed urine collectiontimed urine collection " "

" " Defined Defined as the presence of albumin in the as the presence of albumin in the urine above the normal level but below urine above the normal level but below

the detectable range of conventional urine the detectable range of conventional urine dipstick methodsdipstick methods " "

MicroalbuminuriaMicroalbuminuria

" " The The mean level of albumin excretion mean level of albumin excretion has has been shown fall between been shown fall between 8 and 10 mg/g 8 and 10 mg/g

creatinine creatinine in children in children >6 yr old>6 yr old " "


Cont.Cont.

" " Microalbuminuria in children has been Microalbuminuria in children has been found to be found to be associated with obesity associated with obesity and and

to to predictpredict, with reasonable specificity, , with reasonable specificity, the the development of diabetic nephropathy development of diabetic nephropathy

inin type 1 diabetes mellitustype 1 diabetes mellitus " "

Causes of proteinuriaCauses of proteinuria

" " The majority of children found to have The majority of children found to have positive urinary dipstick values for protein positive urinary dipstick values for protein

have have normal dipstick values on repeated normal dipstick values on repeated measurementsmeasurements " "

1.Transient Proteinuria1.Transient Proteinuria

" " Approximately Approximately 10%10% of children who of children who undergo undergo random urinalysis random urinalysis have have proteinuria proteinuria

by a single dipstick measurementby a single dipstick measurement .. " "

1.Transient Proteinuria(cont.)1.Transient Proteinuria(cont.)

" " Across the school-age spectrum this Across the school-age spectrum this finding occurs more finding occurs more commonly in commonly in

adolescents adolescents than in younger childrenthan in younger children " "

" " In most In most cases, serial testing of the cases, serial testing of the patient’s urine demonstrates patient’s urine demonstrates resolutionresolution

of the abnormality. of the abnormality. ""

http://emedicine.medscape.com/article/984289-overview#a30

1.Transient Proteinuria(cont.)1.Transient Proteinuria(cont.)

" " The proteinuria usually The proteinuria usually does does not exceed 1-2+ on the dipsticknot exceed 1-2+ on the dipstick " "

" " Its Its causecause remains remains elusiveelusive " "

Defined contributing factors include :

Temperature >38.3°C (101°F)

Exercise Heart failure

Dehydration Seizures

Cold exposure Stress

" " No evaluation or therapy No evaluation or therapy is neededis needed " "

" " Orthostatic proteinuria is the Orthostatic proteinuria is the most most common cause of persistent proteinuria common cause of persistent proteinuria in in

school-aged children school-aged children and and adolescentsadolescents " "

2.Orthostatic (Postural) Proteinuria2.Orthostatic (Postural) Proteinuria

" " Occurring in up to Occurring in up to 60% 60% of children with of children with persistent proteinuriapersistent proteinuria " "


2.Orthostatic (Postural) Proteinuria (cont.)2.Orthostatic (Postural) Proteinuria (cont.)

" " Patients with orthostatic proteinuria Patients with orthostatic proteinuria excrete normal or minimally increased excrete normal or minimally increased

amounts amounts of protein in the of protein in the supine positionsupine position.. " "

" " Children with this condition are Children with this condition are usually usually asymptomaticasymptomatic, and the condition is , and the condition is discovered discovered

on routine urinalysison routine urinalysis.. " "

" " In the In the upright positionupright position, urinary protein , urinary protein excretion may be excretion may be increased 10-foldincreased 10-fold, up , up

to 1,000 mg/24 hr (1 g/24 hr).to 1,000 mg/24 hr (1 g/24 hr). " "


""Hematuria, hypertension, hypoalbuminemia, Hematuria, hypertension, hypoalbuminemia, edema, and renal dysfunction edema, and renal dysfunction are absentare absent.. " "


" " The initial evaluation should include an The initial evaluation should include an assessment for orthostatic proteinuriaassessment for orthostatic proteinuria, a , a

condition in which the condition in which the 24-hr urinary protein 24-hr urinary protein excretion rarely exceeds 1 gexcretion rarely exceeds 1 g " "


" " It begins with the collection of a It begins with the collection of a first first morning urine samplemorning urine sample, with subsequent , with subsequent

testing of any urinary abnormalities by a testing of any urinary abnormalities by a complete urinalysis complete urinalysis and and determination of a determination of a

spot protein : creatinine (Pr : Cr) ratiospot protein : creatinine (Pr : Cr) ratio. ""


" " The The absence of proteinuria absence of proteinuria (dipstick (dipstick negative or trace for protein and urine Pr : negative or trace for protein and urine Pr :

Cr ratio <0.2) in the first morning urine Cr ratio <0.2) in the first morning urine sample for sample for 3 consecutive days confirms3 consecutive days confirms the the

diagnosis of orthostatic proteinuriadiagnosis of orthostatic proteinuria " "

" " The The correct collection correct collection of the of the first morning first morning urine urine sample is sample is criticalcritical.. " "


" " The The cause cause of orthostatic proteinuria is of orthostatic proteinuria is unknownunknown, although, although i. Altered renal hemodynamics i. Altered renal hemodynamics ii. Partial renal vein obstruction inii. Partial renal vein obstruction in the upright position are the upright position are possiblepossible causescauses.. " "

" " NoNo further evaluation is necessary, and the further evaluation is necessary, and the patient and family should be patient and family should be reassuredreassured of of

the the benign nature benign nature of this condition. of this condition. ""

3.Fixed Proteinuria3.Fixed Proteinuria

" " Fixed proteinuria Fixed proteinuria indicates renal diseaseindicates renal disease and may be caused by either :and may be caused by either : glomerularglomerular or or tubular disorderstubular disorders " "

" " Persons found to have:Persons found to have: Significant proteinuria Significant proteinuria on a on a first morning first morning urine sample urine sample on on 3 consecutive days 3 consecutive days (>1+ (>1+ on dipstick ,urine specific gravity >1.015 on dipstick ,urine specific gravity >1.015

or protein : creatinine ratio >0.2) or protein : creatinine ratio >0.2) ""

Initial evaluationInitial evaluation

" " Initial evaluation of a child with fixedInitial evaluation of a child with fixed proteinuria should include :proteinuria should include :

- Measurement of - Measurement of serum creatinineserum creatinine and and electrolyte panel electrolyte panel

- - First morning urine First morning urine protein :creatinineprotein :creatinine

ratio ratio - - Serum albumin Serum albumin level level

- - ComplementComplement levels. levels. " "

I. Glomerular ProteinuriaI. Glomerular Proteinuria

" " Glomerular proteinuria can Glomerular proteinuria can rangerange from from <1 g to<1 g to >30 g/24 hr>30 g/24 hr.. " "

" " Glomerular proteinuria results from Glomerular proteinuria results from alterations in alterations in the permeabilitythe permeability of any of the layers of the of any of the layers of the

glomerular capillary wall to normally filtered glomerular capillary wall to normally filtered proteins and occurs in a variety of renal diseases. proteins and occurs in a variety of renal diseases. ""


I. Glomerular Proteinuria (cont.)I. Glomerular Proteinuria (cont.)

" " Glomerular proteinuria should be Glomerular proteinuria should be suspectedsuspected in any patient with:in any patient with:

- First morning - First morning urine protein : creatinineurine protein : creatinine ratio >1.0ratio >1.0, or , or

- Proteinuria of any degree- Proteinuria of any degree, accompanied by:, accompanied by: i. i. HypertensionHypertension

ii. ii. HematuriaHematuria iii. iii. EdemaEdema or or

iv. iv. Renal dysfunctionRenal dysfunction " "

I. Glomerular Proteinuria (cont.)I. Glomerular Proteinuria (cont.)Disorders characterized Disorders characterized primarily by proteinuriaprimarily by proteinuria include:(include:(MAD MP2 SIFS))

IIdiopathic (minimal change)diopathic (minimal change) nephrotic syndromenephrotic syndrome

MMembranoembranoPProliferativeroliferative glomerulonephritisglomerulonephritis

FFocal ocal SSegmentalegmental glomerulosclerosisglomerulosclerosis

AAmyloidosismyloidosis

MMesangial esangial PProliferativeroliferative glomerulonephritisglomerulonephritis

DDiabetic nephropathyiabetic nephropathy

MMembranous nephropathyembranous nephropathy SSickle cell nephropathyickle cell nephropathy

I. Glomerular Proteinuria (cont.)I. Glomerular Proteinuria (cont.)

Renal disorders that Renal disorders that proteinuria proteinuria can be can be a prominent a prominent feature feature includeinclude::

acute Postinfectious glomerulonephritis

Immunoglobulin A nephropathy

Lupus nephritis

Henoch-Schönlein purpura nephritis

Alport syndrome

DiagnosisDiagnosis

" " In asymptomatic patients with low-grade proteinuria (protein: creatinine ratio 0.2-1.0) in whom all other

findings are normal, renal biopsy might not be indicated because:

* Underlying process may be transient or resolving or

*Specific pathologic features of a chronic kidney disease might not yet be apparent. Such patients should have periodic re- evaluation (every 4-6 months unless the patient is symptomatic) ""

Diagnosis Diagnosis ((Cont.)

" " Consisting of:Consisting of:• Physical examination Physical examination and and blood blood

pressure pressure determinationdetermination• Urinalysis Urinalysis

• Measurement of Measurement of serum creatinine serum creatinine • First morning voided First morning voided urine protein :urine protein :

creatinine ratiocreatinine ratio.. " "

Indications for renal biopsyIndications for renal biopsy

" " Include:Include:• Increasing proteinuria Increasing proteinuria

(protein : creatinine >1.0)(protein : creatinine >1.0) and/orand/or

•The The development of development of :: i. i. HematuriaHematuria

ii. ii. HypertensionHypertension iii. iii. Diminished renal functionDiminished renal function " "

1. http://www.hopkinschildrens.org/proteinuria.aspx2. http://emedicine.medscape.com/article/984289-

overview#a30

ii. Tubular Proteinuria(cont.)ii. Tubular Proteinuria(cont.)

" " In the healthy stateIn the healthy state, large amounts of proteins of , large amounts of proteins of lower molecular weight than albumin are lower molecular weight than albumin are filtered filtered

by the glomerulus by the glomerulus and and reabsorbed in the proximal reabsorbed in the proximal tubuletubule " "

" " A variety of renal disorders that primarily A variety of renal disorders that primarily involve the tubulointerstitial compartment of the involve the tubulointerstitial compartment of the

kidney can cause kidney can cause low-grade fixed proteinuria low-grade fixed proteinuria (protein : creatinine ratio (protein : creatinine ratio <1.0<1.0. . ""


" " Injury to the proximal tubules Injury to the proximal tubules can result in:can result in:• Diminished reabsorptive capacity Diminished reabsorptive capacity

• Loss of these low molecular weight proteinsLoss of these low molecular weight proteins in the urinein the urine " "

" " Tubular proteinuria may be seen in Tubular proteinuria may be seen in acquiredacquiredand and inherited disorders inherited disorders and may be and may be associated with associated with other defects of proximal tubular functionother defects of proximal tubular function, such as, such as

the Fanconi syndrome. the Fanconi syndrome. (glycosuria, phosphaturia, bicarbonate (glycosuria, phosphaturia, bicarbonate

wasting, and aminoaciduria).wasting, and aminoaciduria). " "


" " Asymptomatic Asymptomatic patients having persistent persistent proteinuria proteinuria generally have glomerular rather than glomerular rather than

tubular proteinuriatubular proteinuria " "

" " Tubular proteinuria is a consistent finding among patients with the X-linked tubular syndromeX-linked tubular syndrome, Dent Dent diseasedisease, caused by mutations of the renal chloride

channel " "

ii. Tubular ii. Tubular Proteinuria(cont.)Proteinuria(cont.) Tubular diseases Tubular diseases

Cystinosis Heavy metal poisoning

Wilson disease Acute tubular necrosis

Lowe syndrome Renal dysplasia

Dent disease (X-linked recessive nephrolithiasis)

Polycystic kidney disease

Galactosemia Reflux nephropathy

Tubulointerstitial nephritis


" " In occult In occult cases , glomerular and tubular cases , glomerular and tubular proteinuria can be distinguished by proteinuria can be distinguished by electrophoresis electrophoresis of the urine.of the urine. " "

" " In In tubular proteinuriatubular proteinuria, , little or no albumin little or no albumin is detected, whereas in is detected, whereas in glomerular glomerular

proteinuria proteinuria the the major protein is albuminmajor protein is albumin. " "

Asymptomatic proteinuriaSummary .1 Summary .1

Hematuria or other signs of

kidney disease

Nonrenal diseases Recheck when resolves

Isolated proteinuriaCollected 12 –hrRecumbent urine

<50 mg/m2/12hr

Isolated intermittent Proteinuria

or orthostatic proteinuria

Reassure

90%

No

No

Yes

Asymptomatic proteinuria

Summary.2Summary.2


kidney disease

Nonrenal diseases


50 - 200mg/m2/12hr

Limited evaluationBUN ,Creatinine ,S.electrolyte

sSpot UPr: UCr ratio , S .Total

proteinC3 ,C4 ,ASOT, Lupus

serology (selected cases)Renal imaging ,index of

tubular proteinuria

Follow -up 5%

No

No

Normal

Asymptomatic proteinuria

SummarySummary


kidney disease

Nonrenal diseases


>200mg/m2/12hr

50 - 200mg/m2/12hr

Limited evaluationBUN ,Creatinine ,S.electrolytes

Spot UPr: UCr ratio , S .Total proteinC3 ,C4 ,ASOT, Lupus serology

(selected cases)Renal imaging ,index of tubular

proteinuria

•Evaluation•Consider referral•S .Total protein•HIV status•Fractionated 24-hr urine collection•S. Albumin•S. Cholesterol•ASOT•C3,C4•ANA , anti-DNA•GFR•Renal imaging•Renal biopsy

Abnormal

Yes

5%

No

No

References

1. Mori Y, Hiraoka M, Suganuma N, Tsukahara H, Yoshida H, Mayumi M. Urinary creatinine excretion and protein/creatinine ratios vary by body size and gender in children. Pediatr Nephrol. May 2006;21(5):683-7.

2. American Academy of Pediatrics. Hagan JF, Shaw JS, Duncan PM, eds. Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents. 3rd Ed. Elk Grove, IL: American Academy of Pediatrics; 2008.

3. http://www.aafp.org/afp/2010/0915/p645.html4. http://www.fpnotebook.com/Urology/Peds/PrtnrInChldrn.htm5. http://www.hindawi.com/journals/ijped/2012/768142/6. http://www.uptodate.com/contents/evaluation-of-proteinuria-in-children7. http://www.hopkinschildrens.org/proteinuria.aspx8. http://www.rightdiagnosis.com/symptoms/proteinuria_in_children/common.htm9. http://emedicine.medscape.com/article/984289-overview#a3010. http://brightfutures.aap.org/3rd_edition_guidelines_and_pocket_guide.html11. http://www.annualreviews.org/doi/abs/10.1146/annurev.physiol.67.031103.154845?

journalCode=physiol

introduction to a child with proteinuria

Health & Medicine

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