Evaluation of Proteinuria in the
Pediatric Patient
Alicia M. Neu, M.D.
Division of Pediatric Nephrology
Definition of Abnormal Proteinuria
• Adults: >150 mg/24 hours
• Children: >4 mg/m2/hour
Sources of “Normal” Proteinuria
• Plasma proteins filtered at the glomerulus
• Proteins excreted by renal tubular cells
• Proteins secreted by the lining of the bladder and
urethra
Mechanisms of Abnormal Proteinuria
•
•
•
•
•
Overflow proteinuria
Increased glomerular permeability
Tubular proteinuria
Tissue proteinuria
Altered renal hemodynamics
Evaluation of Proteinuria
• Qualitative testing- the urine dipstick
– measures primarily albumin
– false positives with alkaline pH
– results affected by concentration of urine
Evaluation of Proteinuria
• Timed urine collection for total protein and
creatinine
– normal < 4 mg/m2/hour
– significant 4-40 mg/m2/hour
– nephrotic range > 40 mg/m2/hour
Evaluation of Proteinuria
Nephrotic range proteinuria may occur with or
without the nephrotic syndrome, but almost
always signifies glomerular disease.
Evaluation of Proteinuria
• Fractionated urine collection
3 separate collections:
8 am-4 pm
4 pm-12 midnight
12 midnight-8 am
Separate measurement of urinary total protein and
creatinine on each collection
Look for increasing proteinuria during the day, but
normal overnight
Evaluation of Proteinuria
• Random urine protein/creatinine :
Age
<2 y
2-13 y
>13 y
Uprotein/Ucreatinine
NORMAL
NEPHROTIC
<.492
>1.5
<.178
>1.5
<.178
>1.5
Evaluation of Proteinuria
• Urinary microalbumin
Typical quantitative tests measure total protein and have
lower limit of detection of 5 mg/dl
“Urinary microalbumin” tests measure only albumin and
lower limit of detection is 3 mg/L (.3 mg/dl)
Normal for children 27 mcg/mg creatinine
Evaluation of Proteinuria
• Microscopic urinalysis: rbc, wbc, casts
• H&P: attention to clues for underlying systemic
disease, chronic renal disease, risk factors for
HIV, Hepatitis
• Other labs: CBC, CMP, PO4, C3, C4, ANA,
HIV, Hepatitis B, C
• Consider renal ultrasound
Indications for Referral
•
•
•
•
Abnormal renal function
Abnormal serologies
Significant proteinuria that does not “fractionate”
+ Nephrotic syndrome, especially atypical
Indications for Renal Biopsy
• Significant or nephrotic range proteinuria without
the nephrotic syndrome (in adolescent patient
confirm that urine does not “fractionate”)
Indications for Renal Biopsy
• Nephrotic range proteinuria with the nephrotic
syndrome and any of the following:
– gross hematuria
– age < 2y, > 12 y
– abnormal renal function, serologies
CASE PRESENTATIONS
Case I
MN is a 14 yo BM noted on a sports PE to have 4+
proteinuria. PMH neg, ROS neg. Plays lacrosse
and soccer.
Case I
PE WT 55 kg; SA 1.1m2
BP 118/70. PE wnl
U/A: S.G 1.015, pH 5.5, 4+ protein, - heme, glucose
Microanalysis- neg
What would you do next ?
• Monitor without further w/u or therapy ?
• Perform “screening” laboratory studies ?
• Treat empirically with steroids ?
Case I
24 hour urine: 481 mg protein
(18 mg/m2/h)
Na 136, K 3.9, Cl 108, HCO3 24, BUN 19, Cr 0.7, TP 7.0,
Alb 3.9, Chol 112
C3 99, C4 18, ANA neg
HIV neg
Hep B neg
Renal ultrasound normal
What would you do next ?
• Monitor without further w/u or therapy ?
• Perform further laboratory studies ?
• Treat empirically with steroids ?
Case I
• Fractionated Urine:
8am- 4pm:
16 mg/m2/h
4pm-12am:
22 mg/m2/h
12am-8am:
3 mg/m2/h
Orthostatic Proteinuria
• Accounts for 60% of all children with proteinuria,
probably higher in adolescents*
• Usually < 1 g proteinuria/day, nephrotic range extremely
unusual
• Best diagnosed with a fractionated 24 hour urine (vs 1st
am void)
• Should document normal renal function, BP
* J Pediatric, 1976
Case II
DJ is a 12 yo AA F who presents to your clinic with
a 3 d hx of periorbital edema, and lower extremity
edema. His PMH is notable only for a URI 2-3
weeks prior to the onset of swelling.
Case II
PE: Wt 35 kg SA 1.0 m2
BP 121/82 P 90 RR 18
+ periorbital edema, mild abdominal fullness, labial edema,
LE edema
U/A: SG 1.020, pH 6.0, 3+ protein, - heme,
- glucose
Microanalysis- neg
What would you do next ?
• Monitor without further w/u or therapy ?
• Perform “screening” laboratory studies ?
• Treat empirically with steroids ?
Case II
24 hour urine: 1300 mg protein
77 mg/m2/h
Na 131; Cl 103; K 4.1; BUN 10; Cr 0.6
TP 4.0; Alb 1.5; Chol 375
C3 103; C4 24; ANA neg
Hep B S Ag neg, Hep C Ab neg, HIV neg
Renal ultrasound normal
CXR normal
What would you do next ?
• Monitor without further w/u or therapy ?
• Perform further laboratory studies ?
• Treat empirically with steroids ?
Case II
• Treated with 2 mg/kg/day oral steroids
• Within 2 weeks, urine protein negative, edema
gone
• Successfully tapered off of steroids (after 6 weeks
of daily and 6 weeks of qod). Has relapse 2-3
times/year
• Presumptive Dx: INS
Idiopathic Nephrotic Syndrome
• Children 2-6 years, normal renal function, neg
serologies
• May have a number of underlying pathologic
lesions
• Response to steroids best predictor of underlying
pathology and prognosis
• 93 % will respond to steroids. 7% of initial nonresponders will eventually respond
• Biopsy: non-responder, steroid-dependent,
frequent relapser
Case III
• KG is an 15 yo previously healthy WM who
presents with 3 day history of low grade fever,
malaise, myalgias, abdominal discomfort and
diarrhea.
Case III
• PE- Wt 65 kg, SA 1.1 m2, BP 119/62 Afebrile
He is tired appearing, but otherwise in NAD. PE notable
only for mild dehydration and mild, diffuse abdominal
tenderness without guarding or rebound.
UA: SG 1.010, pH 6.0, 4+ protein, small hgb, - glucose,
trace ketones
Microanalysis-hyaline casts
What would you do next ?
• Monitor without further w/u or therapy ?
• Perform “screening” laboratory studies ?
• Treat empirically with steroids ?
Case III
• Diagnosed with viral syndrome, advised to force
po fluids and return for follow up in several days.
• On f/u- PE wnl, symptoms resolved.
• Repeat UA S.G. 1.010, 3+ protein, sm hgb
• Follow up UA 2 weeks later- unchanged
What would you do next ?
• Monitor without further w/u or therapy ?
• Perform “screening” laboratory studies ?
• Treat empirically with steroids ?
Case III
24 hour urine: 900 mg protein
47 mg/m2/h
Na 138; Cl 103; K 4.1; BUN 80; Cr 2.6
TP 7.0; Alb 4.0, Calcium 8.0, Phosphate 5.5
WBC 12,200, Hgb 8.0, Plt 325,000
C3 103; C4 24; ANA neg
Hep B, C neg
HIV neg
What would you do next ?
• Monitor without further w/u or therapy ?
• Perform further laboratory studies ?
• Treat empirically with steroids ?
Case III
• Renal ultrasound- small kidneys bilaterally with
hydronephrosis
• VCUG- bilateral grade V reflux
Reflux Nephropathy
• Together with obstructive uropathy is leading
cause of end-stage renal disease in childhood
• Typically presents with febrile urinary tract
infection, may be diagnosed in utero
• Although UTI felt to contribute to renal injury,
there is not a direct correlation between UTI and
progression
• Genetic factors also involved