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?

• Hematuria• Hypertension• Oliguria• Increased Cr

Nephritis Nephrosis

• Edema• Nephrotic range

proteinuria• Low albumin• Hypercholestrolemia

Rapidly Progressive Glomerulonephritis (RPGN)

RPGN

• Post- strep GN• IgA nephropathy• Lupus• HSP

Immune Complex Anti- GBM

• Goodpasture’s disease

• Wegner’s granulomatosis

• Microscopic polyangiitis

• Polyartritis nodosa

Pauci- immune

RPGN

• Post- strep GN• IgA nephropathy• HSP• Lupus

Immune Complex Anti- GBM

• Goodpasture’s disease

• Wegner’s granulomatosis

• Microscopic polyangiitis

• Polyartritis nodosa

Pauci- immune

• ASO, anti-DNase

• Immunoglobulins

• ANA, anti-ds DNA,

C3, C4

• ANCA • Anti- GBM

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 incontinence3. Food intake: beet4. Drugs: rifampin, nitrofurantoin, ibuprofen5. IgA: gross hematuria onset while having colds6. post strep: history of sore throat, tonsillitis, skin infection7. HUS: diarrhea, pallor, fatigue, SOB8. HSP: pupuric skin rash over legs and buttocks (palpable), join swelling/pain, abdominal

pain/bloody stools9. Goodpasture/Wegners: hemoptysis, cough, SOB10. SLE/ vasculitis: butterfly rash, discoid rash, mouth ulcers, photosensitivity, CNS

seizures/psychosis, join swelling11. Kidney stones: renal colic, radiation to groins, past history or family history of stones12. Anatomic: antenatal U/S, single umbilical artery, abdominal swelling13 Hereditary: family history of deafness, family member with hematuria14. Bleeding diathesis: hemarthrosis, epistaxis, petechaie, heavy periods in older girls15. Problems with high blood pressure16. 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)

• Urine prot/cr:

> 20 mg/mmol

• 24 h urine collection:

> 100 mg/m2/day

> 4 mg/m2/hr

Non- nephrotic Nephrotic

• Urine prot/cr

> 200 mg/mmol

• 24 h urine collection:

> 1 g/m2/ day

> 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

• Congenital:

-Finish- type

- TORCH infection

• Nephritis:

- postinfectious GN

- lupus

- Wegner

- HUS

- Goodpasture

• Nephrotic:

- Minimal change

- FSGS

- MPGN

• Drugs: captopril

• Neoplasia

• Renal vein throbosis

Glomerular Protein overload

• Hemolysis• Rhabdomyolysis• Light chain

• ATN• Fanconi Syndrome• Cystic/dysplastic• Interstial nephritis• Pyelonephritis

Tubualr absorption

Proteinuria

• Congenital:

-Finish- type

- TORCH infection

• Nephritis:

- postinfectious GN

- lupus

- Wegner

- HUS

- Goodpasture

• Nephrotic:

- Minimal change

- FSGS

- MPGN

• Drugs: captopril

• Neoplasia

• Renal vein throbosis

Glomerular Protein overload

• Hemolysis• Rhabdomyolysis• Light chain

• ATN• Fanconi Syndrome• Cystic/dysplastic• Interstial nephritis• Pyelonephritis

Tubualr absorption

Urine electrophoresis:

• Glomerular: albumin

•Tubular: other proteins..

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