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Morning Report

August 31, 2015


Kirsten Graff, MD, PGY-2

Case
6 year old previously healthy girl presents with 1
week of dark urine
Parents first noticed dark urine on 7/4/15
Note that it starts out light, but darkens throughout the
day, and is bright red toward the end of the day
No dysuria, urgency, or increased frequency

HPI
Multiple UAs positive for blood within 6 weeks
UAs also occasionally positive for protein
All UAs notable for high specific gravity

PMH and SH
Previously healthy
Lives with parents and 3 older sisters
Recently started first grade

Physical Exam
General: The patient is alert and in no acute distress. Notable anxiety
when faced with GU exam.
HEENT: PERRL, EOMI, no LAD
Cardiovascular: RRR, normal S1 and S2 with no murmur, rub, or
gallop. Peripheral pulses are normal in all extremities, capillary refill
< 2 seconds.
Respiratory: Normal breath sounds in all lung fields examined. Air
movement bilaterally is symmetric with no increased work of
breathing, or retractions. No wheezes crackles or rhonchi were heard.
Abdomen: Soft, non-tender, non-distended; normal bowel sounds, no
hepatosplenomegaly. No significant stool burden palpated
GU/rectal: normal labia majora and minora, without erythema,
swelling or abrasion; urethral opening without abrasions, lesions, or
erythema
Extremities: Warm and well perfused. Full ROM, no edema
Neurologic: Cranial nerves II through XII are grossly intact without
focal deficits. Strength and gait appear normal.
Skin: No significant rashes or other lesions.

Family History
Mother with history of kidney stones x 2, both in
the third trimester of pregnancy
Father with history of multiple kidney stones and
bouts of prostatitis

Differential Diagnosis
Infectious
UTIs
HUS
Schistosomiasis

Trauma
Urethral, bladder,
kidney

Renal

Hypercalciuria
IgA Nephropathy
PIGN
Familial Hematuria
Alport, Thin
basement
membrane

Heme/Onc
Transitional cell
carcinoma
Wilms tumor

CV/vascular
Bacterial
endocarditis
Nutcracker syndrome
HSP

Rheum
SLE

Poisoning
Heavy metals,
mushrooms,
naphthalene, arsenic

Labs
UA: brown, SG > 1.030, pH 5.5, large Hgb, 2+
protein, negative glucose, ketones, nitrites and
leukocyte esterase
CMP: Na 142, K 4.6, CL 111, CO2 23, BUN 10, Cr
0.36, Gluc 86, Ca 9.9, Prot 6.9, Alb 4.5, T bili 0.3,
Alk phos 225, ALT 13, AST 35
Complement component C3: 92
ASO: 55 (0-199)
DNAse B Antibody: 380 (0-250)
Calcium/Creatinine ratio in urine: 0.24 (<0.21)

Imaging
Renal ultrasound
Left SFU grade 1 hydronephrosis
No calculi
No renal masses

Nephrology consult
Urine microscopy at clinic visit:

Nephrology consult
Urine microscopy at clinic visit:

Interesting areas of increased density in numerous RBCs in urine

Nephrology consult
Urine microscopy at clinic visit:

Dysmorphic RBCs consistent with glomerular source of RBCs.

Diagnosis?
Likely secondary to hypercalciuria, particularly in
the setting of strong family history of kidney
stones
However, dysmorphic RBCs raise the possibility of
a familial cause of hematuria
Both parents attended visit, both UAs negative for blood

Odd apparent nucleated RBCs on microscopy


Plan to follow up in 3 months, and obtain a CBC
with manual diff. Also counseled on proper
hydration, and provided a school note for
unrestricted access to water bottle and restroom
at school.

Gross hematuria
Is hemoglobin detected in the urine?
Urinary dipstick for blood
If positive, likely cause is blood, free hemoglobin or
myoglobin
Urine centrifugation
If sediment is red/brown, etiology is likely blood
If supernatant is red/brown, etiology is not RBCs
(possibly hemoglobin or myoglobin)
Microscopic examination of the sediment confirms
presence of red blood cells

Gross hematuria
See table: Causes of heme-negative red urine in UpToDate
article: Evaluation of gross hematuria in children

Etiology-Gross hematuria

UTI
Irritation of meatus or perineum
Trauma
Less common causes:

Nephrolithiasis
Sickle cell disease/trait
Coagulopathy
Glomerular disease
Post-infectious glomerulonephritis
IgA nephropathy
Malignancies
Wilms tumor
Transitional cell carcinoma of the bladder
Drug induced hemorrhagic cystitis
cyclophosphamide

Etiology-Gross hematuria
10 year retrospective review
342 children presenting with gross hematuria to pediatric
urologic center from 1994-2004

15% Urethral irritation or trauma


14% Urinary tract infection
13% Congenital anomalies
Vesicoureteral reflux
Posterior urethral valves
Ureteropelvic junction obstruction

5% Nephrolithiasis
1% Malignancy
Greenfield SP et al. Gross hematuria in children: a ten-year review. Urology.
2007;69(1):166

Etiology-Gross hematuria
82 children referred to pediatric nephrology center
29% Glomerular cause
IgA nephropathy (n=13)
Alport syndrome (n=9)

37% Non-glomerular etiology


Hypercalciuria (n=9)
Urethral irritation or trauma (n=8)
Hemorrhagic cystitis (n=7)

34% No cause identified

Youn, T et al. Clinical spectrum of gross hematuria in pediatric patients. Clinical Pediatrics.
2006;45(2):135.

Etiology-Gross and Microscopic


Hematuria
582 children referred to Indiana University for
asymptomatic gross or microscopic hematuria
between 1979-2002

Bergstein J, Leiser J, Andreoli S. The Clinical Significance of Asymptomatic Gross and


Microscopic Hematuria in Children.Arch Pediatr Adolesc Med.2005;159(4):353-355

Workup-Gross hematuria
Urinalysis with microscopy (!!)
Urine culture
Urine calcium to creatinine ratio
If elevated, consider 24 hour urine collection

Renal ultrasound
If considering PIGN
C3 and C4
ASO/Anti DNAse B (more sensitive)

Further workup to consider:


Renal function panel
CBC with manual diff
C3 level

Workup-Microscopic
hematuria
Urinalysis with microscopy (!!)
Dipsticks prone to false-positives
> 5 RBCs per HPF (40x magnification)
Repeat to evaluate for persistence (defined as a positive repeat test in 6 months)

Urine culture
Urine calcium to creatinine ratio
If elevated, consider 24 hour urine collection

If considering PIGN
C3 and C4
ASO/Anti DNAse B (more sensitive)

If considering SLE
C3 and C4
ANA/Double stranded DNA

Further workup to consider:


Renal function panel
CBC with manual diff

When to refer:
If persistent microscopic hematuria (> 5 per HPF
for > 6 months), consider referral for review of
microscopy
Casts, couplets/chains, dysmorphic RBCs on urine
microscopy
Persistent proteinuria (particularly in a well
hydrated child)
Lab abnormalities
Ultrasound abnormalities
Elevated BP

Algorithm for gross or symptomatic


microscopic hematuria in children
In UpToDate article: Evaluation of gross hematuria in children

Board question
The parents of a 10 year old girl present for a 2nd opinion. She has
been having asymptomatic microscopic hematuria for 18 months. Her
records show normal PE, normal renal US, and normal serum
chemistries. Multiple UAs show 4+ blood but dipstick and 20-50 RBCs
per HPF. There is no family history of autoimmune diseases or renal
failure.
Her PE reveals: T 37.9, HR 76, RR 17, BP 110/60; normal growth and
physical exam. UA reveals SG 1.035, pH 6.0, 4+ blood, otherwise
negative. Her urine microscopy shows 50-100 RBCs/HPF, no crystals
or bacteria.
Of the following, you are MOST likely to inform the parents that:
A.
B.
C.
D.
E.

Asymptomatic microscopic hematuria is uncommon in schoolchildren


Persistent microscopic hematuria indicates significant risk for renal
failure in the future
Proteinuria would increase her risk for progressive renal disease
She will need a renal biopsy for evaluation of her hematuria
She will need a urology referral

Board question
The parents of a 10 year old girl present for a 2nd opinion. She has
been having asymptomatic microscopic hematuria for 18 months. Her
records show normal PE, normal renal US, and normal serum
chemistries. Multiple UAs show 4+ blood but dipstick and 20-50 RBCs
per HPF. There is no family history of autoimmune diseases or renal
failure.
Her PE reveals: T 37.9, HR 76, RR 17, BP 110/60; normal growth and
physical exam. UA reveals SG 1.035, pH 6.0, 4+ blood, otherwise
negative. Her urine microscopy shows 50-100 RBCs/HPF, no crystals
or bacteria.
Of the following, you are MOST likely to inform the parents that:
A.
B.
C.
D.
E.

Asymptomatic microscopic hematuria is uncommon in schoolchildren


Persistent microscopic hematuria indicates significant risk for renal
failure in the future
Proteinuria would increase her risk for progressive renal disease
She will need a renal biopsy for evaluation of her hematuria
She will need a urology referral

Prep Pearls
Isolated asymptomatic microscopic hematuria (>5
RBCs/HPF) is relatively common in school aged children
with hematuria, and such patients have a low risk for
systemic disease or abnormalities of the urinary tract
Thin basement membrane disease or benign familial
hematuria is a benign genetic condition and is one of the
most common causes for isolated asymptomatic
hematuria
Patients with persistent microscopic hematuria (hematuria
present for > 6 months) need to be monitored periodically
for the development of proteinuria, hypertension or
deteriorating renal function. This may be indicative of
progressive renal pathology requiring detailed evaluation.

References
Thanks to Dr Grinsell and Dr Seamon
Bergstein J, Leiser J, Andreoli S. The Clinical
Significance of Asymptomatic Gross and
Microscopic Hematuria in Children.Arch Pediatr
Adolesc Med.2005;159(4):353-355
Greenfield SP et al. Gross hematuria in children: a
ten-year review. Urology. 2007;69(1):166
UpToDate
Youn, T et al. Clinical spectrum of gross hematuria
in pediatric patients. Clinical Pediatrics.
2006;45(2):135