HEMATURIA in children and proteinuria in children

Pediatric Blood in utinr

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

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

Orthostatic proteinuria

4. Case 1

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

Orthostatic proteinuria

5. ed |

specific gravity ov | BER.
LLC

pH 2 | | ge "à

leukocyte leuhocytes 7
69-100 ec

esterase RE Saco
itri nilrite
nitrite ple
prorein
protein 30-69 sec
givesso
glucose hrs
ketones:
ketones ae

ili srobeino gen
urobilinogen “ya

ilirubi be
bilirubin aocoses

blood

Blood
30-60 500

hemoglobin ojala.
from

=) 20 mm

TN

color compensation
used for balance

6. Table 1 Causes of red urine without hematuria?

Drugs
Chloroquine
Ibuprofen
Iron sorbitol
Nitrofurantoin
Phenazopyridine
Phenolphthalein

Foods
Beets
Blackberries
Food coloring

Metabolites
Bile pigments
Homogentisic acid
Melanin
Methemoglobin
Porphyrin
Tyrosine
Urates

Current Opinion in Pediatrics 2008, 20:140-144

7. Case 2

« 1 year old infant with failure to thrive. Both
height and weight are below the 3"
percentile. He has sings of rickets in
exam.

Urine dip: Prot 3+ , Glu 2+

8. Case 2

« 1 year old infant with failure to thrive. Both
height and weight are below the 3"
percentile. He has sings of rickets in
exam.

Urine dip: Prot 3+ , Glu 2+

9. Case 3

* Urine prot/cr 1500 mg/mmol
+ Serum albumin 15 g/l
« High cholesterol

10. Case 3

* Urine prot/cr 1500 mg/mmol
+ Serum albumin 15 g/l
« High cholesterol

11. HPF= x 400

12. Case 5

+ Urine positive for adenovirus

13. Case 5

+ Urine positive for adenovirus

14. Case 6

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

15. a

YN
WA
~~ /

Y :
N
Ca

N SER

Calcium Oxalate Crystals

Struvite Crystals

phe

Cystine Crystals

16. Case 6

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

17. Case 7

« Send blood for:
C3, C4, ANA, anti-ds DNA

19. Waxy
cast

Cellular
cast

Finely
granular
cast

Coarsely
granular

cast

Renal tubules

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

23. Is it serious?

« Hematuria « Edema

« Hypertension « Nephrotic range
* Oliguria proteinuria
+ Increased Cr + Low albumin

* Hypercholestrolemia

24. Rapidly Progressive
Glomerulonephritis (RPGN)

25. RPGN
_—
Kmmuns Comper | Paus-immune | Ani sem —

Post- strep GN Wegner's * Goodpasture’s
IgA nephropathy granulomatosis disease
Lupus Microscopic
HSP polyangiitis
Polyartritis nodosa

26. __ RPGN

Post- strep GN Wegner's * Goodpasture’s
IgA nephropathy granulomatosis disease

HSP Microscopic

polyangiitis

Polyartritis nodosa

Lupus

+ ASO, anti-DNase + ANCA + Anti- GBM
+ Immunoglobulins

+ ANA, anti-ds DNA,

C3, C4

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

* Diagnosis: clinical suspicion
IgA level 20% sensitivity!
Kidney biopsy- IgA in Immunoflorecence

* Treatment: supportive in mild cases
ACEI in proteinuria
Steroids

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 0157: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!)

. Gross hematuria: onset, duration, progression, aggravating, relieving factors,
associated symptoms

. UTI symptoms: dysuria, frequency, urgency, urge incontinence
. Food intake: beet

. Drugs: rifampin, nitrofurantoin, ibuprofen

. IgA: gross hematuria onset while having colds

. post strep: history of sore throat, tonsillitis, skin infection

. HUS: diarrhea, pallor, fatigue, SOB

E Ae pupune skin rash over legs and buttocks (palpable), join swelling/pain, abdominal
pain/bloody stools

. 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

© ANOnORWND

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
Trace

1+

2+

3+

4+

< 10 mg/dl
10- 20 mg/dl
30 mg/dl
100 mg/dl
300 mg/dl
1000 mg/dl

37. Proteinuria (Quantitative)

« Urine prot/cr: ¢ Urine prot/cr
> 20 mg/mmol > 200 mg/mmol

» 24h urine collection: ||» 24h urine collection:
> 100 mg/m2/day > 1 g/m2/ day
> 4 mg/m2/hr > 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

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

Orthostatic proteinuria

40. 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 3"
percentile. He has sings of rickets in
exam.

Urine dip: Prot 3+ , Glu 2+

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

44. Fanconi Synrome

PCT defect

Proximal renal tubular
acidosis (type II RTA)

Glucosuria
Aminoaciduria
Phosphaturia
hypokalemia

45. Proteinuria

t Protein overload

Congenital: ATN * Hemolysis
-Finish- type : i
_ TORCH infection Fanconi Syndrome ||» Rhabdomyolysis
Nephritis: Cystic/dysplastic + Light chain

- postinfectious GN a mi
postiniectious Interstial nephritis

- lupus
- Wegner Pyelonephritis
- HUS
- Goodpasture
+ Nephrotic: Urine electrophoresis:
- Minimal change
- FSGS
*MPGN «Tubular: other proteins...
» — Drugs: captopril
+ Neoplasia
€ Renal vein throbosis

» Glomerular: albumin

46. Proteinuria

t Protein overload

Congenital: ATN * Hemolysis
-Finish- type : i
_ TORCH infection Fanconi Syndrome ||» Rhabdomyolysis
Nephritis: Cystic/dysplastic + Light chain

- postinfectious GN a mi
postiniectious Interstial nephritis

- lupus
- Wegner Pyelonephritis
- HUS
- Goodpasture
+ Nephrotic: Urine electrophoresis:
- Minimal change
- FSGS
*MPGN «Tubular: other proteins...
» — Drugs: captopril
+ Neoplasia
€ Renal vein throbosis

» Glomerular: albumin

47. Case 3

* Urine prot/cr 1500 mg/mmol
+ Serum albumin 15 g/l
« High cholesterol

48. Case 3

* Urine prot/cr 1500 mg/mmol
+ Serum albumin 15 g/l
« High cholesterol

49. Nephrotic Syndrome

Minimal change disease

Focal segmental glomerulosclerosis
Membranoproliferative
Membranous GN

Infection: HIV, hepatits, syphilis
Lupus, Ig A, HSP, post strep

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: aloumin 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