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Approach to Hematuria and Proteinuria in Children

Approach to Hematuria and Proteinuria in Children

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Approach to Hematuria and Proteinuria in Children

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  1. Approach to Hematuria and Proteinuria in Children Adi Alherbish

  2. 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.

  3. 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?

  4. Case 1 • Urine dipstick: negative

  5. 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

  6. Case 2 • CBC: Hg 80, WBC 5, Plt 180 • Retics: 3% Hemolytic Anemia • Send blood for: Hg electrophoresis, peripheral smear, Coombs test, G6PD

  7. 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

  8. Case 3 • Repeat urinalysis after drinking a bottle of water: Urine SG: 1.015 RBC: 1- 5 /HPF WBC: 0- 5 / HPF

  9. HPF= x 400

  10. 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

  11. Case 5 • Urine positive for adenovirus

  12. 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

  13. Case 6 • In clinic: send urine for Ca/ Cr ratio, citrate, oxalate, uric acid, cystine

  14. 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

  15. Case 7 • Send blood for: C3, C4, ANA, anti-ds DNA

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

  17. The 3 Vital Questions 1 Is it true hematuria? 2 Is it serious (urgent)? 3 What is the cause?

  18. Hematuria Hypertension Oliguria Increased Cr Is it serious? Nephritis Nephrosis • Edema • Nephrotic range proteinuria • Low albumin • Hypercholestrolemia

  19. Rapidly Progressive Glomerulonephritis (RPGN)

  20. Post- strep GN IgA nephropathy Lupus HSP RPGN Immune Complex Pauci- immune Anti- GBM • Wegner’s granulomatosis • Microscopic polyangiitis • Polyartritis nodosa • Goodpasture’s disease

  21. Post- strep GN IgA nephropathy HSP Lupus RPGN Immune Complex Pauci- immune Anti- GBM • Wegner’s granulomatosis • Microscopic polyangiitis • Polyartritis nodosa • Goodpasture’s disease • ASO, anti-DNase • Immunoglobulins • ANA, anti-ds DNA, • C3, C4 • ANCA • Anti- GBM

  22. 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%)

  23. IgA nephropathy • Typical presentation: intermittent gross hematuria that happen during colds • Other: gross hematuria microscopic hematuria nephritis nephrotic syndrome ESRD

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

  25. Henoch Schonlein Purpura(HSP) • Pathology: IgA nephropathy • Clinical: - purpuric rash - arthritis - intestinal edema (intussusception) - hematuria/ nephritis/ nephrosis

  26. 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

  27. 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

  28. Benign familial hematuria(thin basment membrane nephropathy) • Autosomal dominant • Hetrozygous mutation in type IV collagen • Microscopic hematuria • Screen the parents’ urine • Benign course

  29. 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

  30. 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

  31. 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

  32. Urine prot/cr: > 20 mg/mmol 24 h urine collection: > 100 mg/m2/day > 4 mg/m2/hr Proteinuria (Quantitative) Non- nephrotic Nephrotic • Urine prot/cr > 200 mg/mmol • 24 h urine collection: > 1 g/m2/ day > 40 mg/m2/hr

  33. The 3 Vital Questions 1 Is it persistent? 2 Is it nephrotic? 3 What is the cause?

  34. Case 1 • 15 year old, athletic boy • Regular check up: Urine dip: Prot 2+ Urine prot/Cr ratio: 50 mg/mmol • What next?

  35. Case 1 • 8 am: urine prot/Cr ratio- 10 mg/mmol • 4 pm: urine prot/Cr ratio- 50 mg/mmol Orthostatic proteinuria

  36. Non Persistant Proteinuria • Fever • Strenuous exercise • Cold exposure • Epinephrine infusion • Orthostatic

  37. 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+

  38. Derakhshan Ali et al. Saudi J Kidney Dis Transpl. 2007 Oct-Dec;18(4):585-9.

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

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

  41. Congenital: -Finish- type - TORCH infection Nephritis: - postinfectious GN - lupus - Wegner - HUS - Goodpasture Nephrotic: - Minimal change - FSGS - MPGN Drugs: captopril Neoplasia Renal vein throbosis Proteinuria Glomerular Tubualr absorption Protein overload • ATN • Fanconi Syndrome • Cystic/dysplastic • Interstial nephritis • Pyelonephritis • Hemolysis • Rhabdomyolysis • Light chain • Urine electrophoresis: • Glomerular: albumin • Tubular: other proteins..

  42. 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?

  43. Case 3 • Urine prot/cr 1500 mg/mmol • Serum albumin 15 g/l • High cholesterol

  44. Nephrotic Syndrome • Urine Prot/Cr > 200 mg/mmol • Serum albumin < 25 g/l • Edema • Hyperlipedemia

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