Approach%20to%20Hematuria%20and%20Proteinuria%20in%20Children

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Approach to Hematuria and Proteinuria in Children

• Adi Alherbish

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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.

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Case 1

• 14 year old boy presenting with red urine since
  last night. Otherwise healthy. Normal BP, no
  flank pain, no ankle edema.
• Whats the next step?

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Case 1

• Urine dipstick negative

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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

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Case 2

• CBC Hg 80, WBC 5, Plt 180
• Retics 3
• Hemolytic Anemia
• Send blood for Hg electrophoresis, peripheral
  smear, Coombs test, G6PD

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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

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Case 3

• Repeat urinalysis after drinking a bottle of
  water
• Urine SG 1.015
• RBC 1- 5 /HPF
• WBC 0- 5 / HPF

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HPF x 400
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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 gt 100/ HPF
• WBC 10- 25/ HPF

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Case 5

• Urine positive for adenovirus

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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

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Case 6

• In clinic send urine for Ca/ Cr ratio, citrate,
  oxalate, uric acid, cystine
• 
  

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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

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Case 7

• Send blood for
• C3, C4, ANA, anti-ds DNA

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Hematuria

• Presence of gt 5 RBC/ HPF, on more than two
  occasions, in the context of a normal urine
  specific gravity

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The 3 Vital Questions

• 1 Is it true hematuria?
• 2 Is it serious (urgent)?
• 3 What is the cause?

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Is it serious?
Nephritis
Nephrosis

• Hematuria
• Hypertension
• Oliguria
• Increased Cr

• Edema
• Nephrotic range proteinuria
• Low albumin
• Hypercholestrolemia

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Rapidly Progressive Glomerulonephritis (RPGN)
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RPGN
Immune Complex
Anti- GBM
Pauci- immune

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

• Goodpastures disease

• Wegners granulomatosis
• Microscopic polyangiitis
• Polyartritis nodosa

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RPGN
Immune Complex
Anti- GBM
Pauci- immune

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

• Goodpastures disease

• Wegners granulomatosis
• Microscopic polyangiitis
• Polyartritis nodosa

• ASO, anti-DNase
• Immunoglobulins
• ANA, anti-ds DNA,
• C3, C4

• ANCA

• Anti- GBM

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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)

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IgA nephropathy

• Typical presentation intermittent gross
  hematuria that happen during colds
• Other gross hematuria
• microscopic hematuria
• nephritis
• nephrotic syndrome
• ESRD

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IgA nephropathy

• Diagnosis clinical suspicion
• IgA level 20 sensitivity!
• Kidney biopsy- IgA in Immunoflorecence
• Treatment supportive in mild cases
• ACEI in proteinuria
• Steroids

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Henoch Schonlein Purpura(HSP)

• Pathology IgA nephropathy
• Clinical
• - purpuric rash
• - arthritis
• - intestinal edema
• (intussusception)
• - hematuria/ nephritis/
• nephrosis

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Hemolytic Uremic Syndrome

• Pathogenesis
• - typical (d) E. coli O157H7 shiga toxin 1
  induced vascular injury
• - atypical (d-) alternative complement pathway
  defect
• Clinical triad of microangiopathic hemolytic
  anemia, thrombocytopenia, ARF

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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

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Benign familial hematuria(thin basment membrane
nephropathy)

• Autosomal dominant
• Hetrozygous mutation in type IV collagen
• Microscopic hematuria
• Screen the parents urine
• Benign course

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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

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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

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Proteinuria (Urine dip)

• Negative lt 10 mg/dl
• Trace 10- 20 mg/dl
• 1 30 mg/dl
• 2 100 mg/dl
• 3 300 mg/dl
• 4 1000 mg/dl

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Proteinuria (Quantitative)
Non- nephrotic
Nephrotic

• Urine prot/cr
• gt 20 mg/mmol
• 24 h urine collection
• gt 100 mg/m2/day
• gt 4 mg/m2/hr

• Urine prot/cr
• gt 200 mg/mmol
• 24 h urine collection
• gt 1 g/m2/ day
• gt 40 mg/m2/hr

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The 3 Vital Questions

• 1 Is it persistent?
• 2 Is it nephrotic?
• 3 What is the cause?

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Case 1

• 15 year old, athletic boy
• Regular check up
• Urine dip Prot 2
• Urine prot/Cr ratio 50 mg/mmol
• What next?

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Case 1

• 8 am urine prot/Cr ratio- 10 mg/mmol
• 4 pm urine prot/Cr ratio- 50 mg/mmol

Orthostatic proteinuria
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Non Persistant Proteinuria

• Fever
• Strenuous exercise
• Cold exposure
• Epinephrine infusion
• Orthostatic

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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

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Derakhshan Ali et al. Saudi J Kidney Dis Transpl.
2007 Oct-Dec18(4)585-9.
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Fanconi Synrome

• PCT defect
• Proximal renal tubular acidosis (type II RTA)
• Glucosuria
• Aminoaciduria
• Phosphaturia
• hypokalemia

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Proteinuria
Glomerular
Protein overload
Tubualr absorption

• Congenital
• -Finish- type
• - TORCH infection
• Nephritis
• - postinfectious GN
• - lupus
• - Wegner
• - HUS
• - Goodpasture
• Nephrotic
• - Minimal change
• - FSGS
• - MPGN
• Drugs captopril
• Neoplasia
• Renal vein throbosis

• Hemolysis
• Rhabdomyolysis
• Light chain

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

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Proteinuria
Glomerular
Protein overload
Tubualr absorption

• Congenital
• -Finish- type
• - TORCH infection
• Nephritis
• - postinfectious GN
• - lupus
• - Wegner
• - HUS
• - Goodpasture
• Nephrotic
• - Minimal change
• - FSGS
• - MPGN
• Drugs captopril
• Neoplasia
• Renal vein throbosis

• Hemolysis
• Rhabdomyolysis
• Light chain

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

• Urine electrophoresis
• Glomerular albumin
• Tubular other proteins..

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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
• Whats the next step?

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Case 3

• Urine prot/cr 1500 mg/mmol
• Serum albumin 15 g/l
• High cholesterol

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Nephrotic Syndrome

• Urine Prot/Cr gt 200 mg/mmol
• Serum albumin lt 25 g/l
• Edema
• Hyperlipedemia

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Nephrotic Syndrome

• Minimal change disease
• Focal segmental glomerulosclerosis
• Membranoproliferative
• Membranous GN
• Infection HIV, hepatits, syphilis
• Lupus, Ig A, HSP, post strep

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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..

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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