Approach to Hematuria and

Proteinuria in Children
Adi Alherbish
 Objectives
• To be able to define and recognize hematuria
and proteinuria

• To be able to generate a differential diagnosis of

the commonest and most serious causes of
hematuria and proteinuria

• To have a clinical approach to both conditions.

 Case 1
• 14 year old boy presenting with red urine
since last night. Otherwise healthy. Normal
BP, no flank pain, no ankle edema.

• What’s the next step?

 Case 1
• Urine dipstick: negative
 Case 2
• 5 year old boy presenting with pallor, and
shortness of breath.

Urine dip: SG 1.015, Hg 2+, Prot neg,

Urinalysis: RBC 0, WBC 0
 Case 2
• CBC: Hg 80, WBC 5, Plt 180
• Retics: 3%

Hemolytic Anemia

• Send blood for: Hg electrophoresis,

peripheral smear, Coombs test, G6PD
 Case 3
• 14 year old girl, healthy
• Regular check up:
Urine dip: SG 1.035, Hg 2+, Prot trace
Urinalysis: RBC 5- 10 /HPF
WBC 0- 5 / HPF
 Case 3
• Repeat urinalysis after drinking a bottle of
water:
Urine SG: 1.015
RBC: 1- 5 /HPF
WBC: 0- 5 / HPF
HPF= x 400
 Case 5
• 9 year old girl, presenting with fever, rash,
coryza, conjuctivitis, and dark urine.
• Urine dip: SG 1.015, Hg +3, Prot trace
• Urinalysis: RBC > 100/ HPF
WBC 10- 25/ HPF
 Case 5
• Urine positive for adenovirus
 Case 6
• 14 year old girl, presenting with
intermittent, sudden onset left flank pain
and dark urine.
• Urine SG: 1.015, Hg 3+, Prot neg
• Urinalysis: RBC 100/ HPF, WBC 0
Crystals present
 Case 6
• In clinic: send urine for Ca/ Cr ratio, citrate,
oxalate, uric acid, cystine
 Case 7
• 14 year old girl, with hypertension, left
knee arthritis, dark urine, malar rash

• Urine dip: SG 1.010, Hg 2+, Prot 2+

• Urinalysis: RBC 10- 25/ HPF
WBC 0
RBC casts
 Case 7
• Send blood for:
C3, C4, ANA, anti-ds DNA
 Hematuria
• Presence of > 5 RBC/ HPF, on more than
two occasions, in the context of a normal
urine specific gravity
 The 3 Vital Questions
1 Is it true hematuria?
2 Is it serious (urgent)?
3 What is the cause?
 Is it serious?
Nephritis Nephrosis

• Hematuria • Edema
• Hypertension • Nephrotic range
• Oliguria proteinuria
• Increased Cr • Low albumin
• Hypercholestrolemia
 Rapidly Progressive
Glomerulonephritis (RPGN)
 RPGN
Immune Complex Pauci- immune Anti- GBM
• Post- strep GN • Wegner’s • Goodpasture’s
• IgA nephropathy granulomatosis disease
• Lupus • Microscopic
• HSP polyangiitis
• Polyartritis nodosa
 RPGN
Immune Complex Pauci- immune Anti- GBM
• Post- strep GN • Wegner’s • Goodpasture’s
• IgA nephropathy granulomatosis disease
• HSP • Microscopic
• Lupus polyangiitis
• Polyartritis nodosa

• ASO, anti-DNase • ANCA • Anti- GBM

• Immunoglobulins
• ANA, anti-ds DNA,
C3, C4
 Post strep Glomerulonephritis
• Strep pharyngitis, or strep skin infection,
followed 10 to 14 days by microscopic
hematuria, nephritis, or nephrosis

• Diagnosis: positive ASO

low C3 which normalize in 8 weeks

• Management: supportive
• Prognosis: Excellent (Vog et. Al: 137 cohort-
ESRD: none, high Cr 10%)
 IgA nephropathy
• Typical presentation: intermittent gross
hematuria that happen during colds
• Other: gross hematuria
microscopic hematuria
nephritis
nephrotic syndrome
ESRD
 IgA nephropathy
• Diagnosis: clinical suspicion
IgA level 20% sensitivity!
Kidney biopsy- IgA in Immunoflorecence

• Treatment: supportive in mild cases

ACEI in proteinuria
Steroids
 Henoch Schonlein Purpura
(HSP)
• Pathology: IgA nephropathy
• Clinical:
- purpuric rash
- arthritis
- intestinal edema
(intussusception)
- hematuria/ nephritis/
nephrosis
 Hemolytic Uremic Syndrome
• Pathogenesis:
- typical (d+): E. coli O157:H7 shiga toxin 1
induced vascular injury
- atypical (d-): alternative complement
pathway defect
• Clinical: triad of microangiopathic
hemolytic anemia, thrombocytopenia, ARF
 Alport Syndrome
(Hereditary Nephritis)
• Homozygous mutation in
genes encoding type IV
collagen in basement
membrane

• Genetics: 80% X-linked

AR, AD

• Clinical: persistent
microscopic hematuria,
hearing loss, lenticonus
 Benign familial hematuria
(thin basment membrane
nephropathy)
• Autosomal dominant
• Hetrozygous mutation in type IV collagen
• Microscopic hematuria
• Screen the parents’ urine
• Benign course
 Work up for hematuria
(History is important!)
1. Gross hematuria: onset, duration, progression, aggravating, relieving factors,
associated symptoms
2. UTI symptoms: dysuria, frequency, urgency, urge incontinence
3. Food intake: beet
4. Drugs: rifampin, nitrofurantoin, ibuprofen
5. IgA: gross hematuria onset while having colds
6. post strep: history of sore throat, tonsillitis, skin infection
7. HUS: diarrhea, pallor, fatigue, SOB
8. HSP: pupuric skin rash over legs and buttocks (palpable), join swelling/pain, abdominal
pain/bloody stools
9. Goodpasture/Wegners: hemoptysis, cough, SOB
10. SLE/ vasculitis: butterfly rash, discoid rash, mouth ulcers, photosensitivity, CNS
seizures/psychosis, join swelling
11. Kidney stones: renal colic, radiation to groins, past history or family history of stones
12. Anatomic: antenatal U/S, single umbilical artery, abdominal swelling
13 Hereditary: family history of deafness, family member with hematuria
14. Bleeding diathesis: hemarthrosis, epistaxis, petechaie, heavy periods in older girls
15. Problems with high blood pressure
16. Family history: nephritis, kidney failure, transplant, deafness, stones, hematuria,
consanguinity
 Work up for hematuria
• Nephritis: ASO, C3, C4, anti-ds DNA,
ANA, ANCA, anti- GBM
• Kidney and bladder U/S
• Stone work up: urine Ca, Cr, oxalate,
citrate, cystine, uric acid
• Urinalysis in both parents
• Bleeding tendency: PT, PTT, INR
 Proteinuria (Urine dip)
• Negative < 10 mg/dl
• Trace 10- 20 mg/dl
• 1+ 30 mg/dl
• 2+ 100 mg/dl
• 3+ 300 mg/dl
• 4+ 1000 mg/dl
 Proteinuria (Quantitative)
Non- nephrotic Nephrotic

• Urine prot/cr: • Urine prot/cr

> 20 mg/mmol > 200 mg/mmol

• 24 h urine collection: • 24 h urine collection:

> 100 mg/m2/day > 1 g/m2/ day
> 4 mg/m2/hr > 40 mg/m2/hr
 The 3 Vital Questions
1 Is it persistent?
2 Is it nephrotic?
3 What is the cause?
 Case 1
• 15 year old, athletic boy
• Regular check up:
Urine dip: Prot 2+
Urine prot/Cr ratio: 50 mg/mmol

• What next?
 Case 1
• 8 am: urine prot/Cr ratio- 10 mg/mmol
• 4 pm: urine prot/Cr ratio- 50 mg/mmol

Orthostatic proteinuria
 Non Persistant Proteinuria
• Fever
• Strenuous exercise
• Cold exposure
• Epinephrine infusion
• Orthostatic
 Case 2
• 1 year old infant with failure to thrive. Both
height and weight are below the 3rd
percentile. He has sings of rickets in
exam.
• Urine dip: Prot 3+ , Glu 2+
Derakhshan Ali et al. Saudi J Kidney Dis Transpl. 2007 Oct-Dec;18(4):585-9.
 Fanconi Synrome
• PCT defect
• Proximal renal tubular
acidosis (type II RTA)
• Glucosuria
• Aminoaciduria
• Phosphaturia
• hypokalemia
 Proteinuria
Glomerular Tubualr absorption Protein overload

• Congenital: • ATN • Hemolysis

-Finish- type
- TORCH infection • Fanconi Syndrome • Rhabdomyolysis
• Nephritis: • Cystic/dysplastic • Light chain
- postinfectious GN
- lupus
• Interstial nephritis
- Wegner • Pyelonephritis
- HUS
- Goodpasture
• Nephrotic:
- Minimal change
- FSGS
- MPGN
• Drugs: captopril
• Neoplasia
• Renal vein throbosis
 Proteinuria
Glomerular Tubualr absorption Protein overload

• Congenital: • ATN • Hemolysis

-Finish- type
- TORCH infection • Fanconi Syndrome • Rhabdomyolysis
• Nephritis: • Cystic/dysplastic • Light chain
- postinfectious GN
- lupus
• Interstial nephritis
- Wegner • Pyelonephritis
- HUS
- Goodpasture
• Nephrotic: Urine electrophoresis:
- Minimal change
- FSGS • Glomerular: albumin
- MPGN •Tubular: other proteins..
• Drugs: captopril
• Neoplasia
• Renal vein throbosis
 Case 3
• 5 year old boy, presenting with puffy eyes,
enlarged tummy, and feet swelling.
• Exam: normal BP, ascites, pitting edema
• Urine dip: Prot 4+

• What’s the next step?

 Case 3
• Urine prot/cr 1500 mg/mmol
• Serum albumin 15 g/l
• High cholesterol
 Nephrotic Syndrome
• Urine Prot/Cr > 200 mg/mmol
• Serum albumin < 25 g/l
• Edema
• Hyperlipedemia
 Nephrotic Syndrome
• Minimal change disease
• Focal segmental glomerulosclerosis
• Membranoproliferative
• Membranous GN
• Infection: HIV, hepatits, syphilis
• Lupus, Ig A, HSP, post strep
 Initial therapy
• Supportive: albumin 25% and lasix prn
• Salt restriction
• Fluid restriction while nephrotic
• Prednisone 60 mg/m2/day for 6 weeks
followed by 40 mg/m2/day for 6 weeks
then wean..
 Indications for biopsy
• Steroid resistant: fail to enter remission after 8
weeks of therapy

• Steroid dependent: intially enter remission, but

develping relapse while on therapy, or within 2
weeks of steroid discontinuration

• Hematuria
• Increased Cr (when intravasculary repleted)
• Low complement
• Positive lupus serology