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

7. 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

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

9. Case 3 14 year old girl, healthy Regular check up:
Urine dip: SG 1.035, Hg 2+, Prot trace
Urinalysis: RBC /HPF
WBC / HPF

10. Case 3 Repeat urinalysis after drinking a bottle of water:
Urine SG: 1.015
RBC: /HPF
WBC: / HPF

11. HPF= x 400

12. 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 / HPF

13. Case 5
Urine positive for adenovirus

14. 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

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

17. 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 / HPF
WBC 0
RBC casts

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

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

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

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

24. Rapidly Progressive Glomerulonephritis (RPGN)

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

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

27. 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%)

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

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

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

31. 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

32. 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

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

34. 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

35. 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

36. Proteinuria (Urine dip)
Negative < 10 mg/dl
Trace mg/dl
mg/dl
mg/dl
mg/dl
mg/dl

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

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

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

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

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

42. 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+

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

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

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

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

47. 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?

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

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

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

51. 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..

52. 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