1. Orange Urine on Halloween
Eva Delgado, MD
Morning Report

2. Overview Case Presentation Indications for Referral/Admission
Work-up based on Differential
Discussion of Pathophysiology
Treatment and Prognosis
Take Home Points

3. Case Presentation
12 y/o F with OCD develops “orange” urine with sediment.
PMD advises watchful waiting.
No real symptoms – no dysuria, no abd pain, no urgency but some frequency.
PMH + OCD
No known family history
Not yet menstruating.

4. Case Presentation
Orange urine persists x 4 days, so mom makes appointment with PMD.
PMD notes elevated BP, weight gain, and then orders one key test………..
URINALYSIS: + hematuria, + proteinuria
HTN with hematuria, proteinuria implies glomerular origin so need to admit – if only isolate hematuria or isolated proteinuria, would be ok to observe – also think about admitting if there is a story of casts

5. A Word on Urinalysis
UA with >/= 5 RBC/hpf on 3 samples over several weeks = HEMATURIA
Only UA can distinguish between confounders:
Myoglobin, hemoglobin, toxins, foods/coloring
BUT, if you have hematuria and proteinuria, higher likelihood of having renal disease – although you can see this with infection alone………need to look at rest of UA
Massengill, Peds In Review, 2008

6. A Word on Disposition Hematuria AND proteinuria Hypertension
Proteinuria may be due to notable hematuria, BUT..
Combination of both increases risk of renal disease
Hypertension
Can be a symptom of fluid overload warranting diuresis and further observation
PMD sends patient to the ED…..
Boineau and Lewy, Peds in Review, 1989.
Simckes and Spitzer, Ped in Review, 1995.

7. Physical Exam in ED Wt 60kg (↑ over last 6 mos)
VS: T 36.4, P 68, BP 146/80, R 20, 100% O2
Gen: no distress
HEENT: no peri-orbital edema, MMM
Chest: CTA b/l
CV: RRR, no murmur
Abd: soft, NTND
Ext: slight erythema in skin folds, no edema

8. Differential and Work-Up
Urinalysis
Chemistry panel
CBC
C3, C4
ASO +/- Throat swab
Imaging
Do you need a biopsy?
UA – likely looking for RBC casts or dysmorphology
Chem – to look for BUN/Cr and/or electrolyte anomalies
CBC – to look for anemia
C3, C4 to see if there is an immune-mediated event – WHY?
ASO to look for recent strep

9. Thinking of Glomerulonephritis
Clues to look for in H&P:
Edema, discolored urine (in 30-50%), HTN due to ↓GFR and hypervolemia, oliguria
Clues to look for in UA:
+ hematuria, + proteinuria, + casts (60-85%)
RBC dysmorphology implies glomerular damage
Sensitivity 95%, specificity 90%
McCory, Peds in Review, 1983.
Boineau and Lewy, Peds in Review 1989.

10. Glomerulopathy vs. Glomerulonephritis
Nephrotic Syndrome
Glomerulonephritis
Edema
R = Red urine (hematuria)
Proteinuria
O = Oliguria
Hypoproteinemia
P = Proteinuria
Elevated LDL
E = Elevated BP, BUN
Hypercoagulability (↑fibrinogen, factor V)
Low C3 = Post-Strep, Membranoproliferative, SLE
Silverstein, Laughing your way to passing the pediatric boards, 2008.

11. Laboratory Results UA: 3+ blood, 2+ protein, 1+ LE, 0 nitrites,
11-20 WBC, numerous RBC, 1-3 granular casts
Chemistry: BUN/Cr = 17/0.8
CBC: Hbg 11.3, HCT 32.5, MCV 79
C3: 26 (86-184)
C4: 21.5 (20-59)
ASO: 2130 (<400 unit/ml); and + Rapid strep

12. Poststreptococcal GN Most common type of Acute GN
Usually occurs in 5-15 y/o
50% of cases are asymptomatic
Diagnosed by evidence of Group A Strep
ASO titers detectable 2-4 weeks s/p pharyngitis
Anti-DNase-B titers helpful in post-pyoderma type
Simckes and Spitzer, Peds in Review 1995.

13. The Role of Grp A Strep Nephritogenic strains of streptococci
Wall protein M12 in pharyngitis, M49 in pyoderma
These strains pose ~ 15% risk of  PSGN approx 2 weeks after initial infection
Antibiotic treatment to prevent GN?
Simckes and Spitzer, Peds in Review, 1995.
Rodriguez-Iturbe and Musser, J Am Soc Nephrology, 2008

14. The Role of Grp A Strep PANDAS =
Post-infectious Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection
Syndenham’s Chorea and Rheumatic Fever
OCD/Tic disorders shown to emerge or worsen with temporal relation to Grp A Strep infection
PANDAS patients may have higher susceptibility to Grp A Strep infection, + family h/o Rheumatic Fever
Kurlan et al. 121 (6): (2008) Pediatrics

15. Considering the DDX of PSGN
Low C3
80-90% of PSGN cases have low C3 x 2 mos
Also seen in GN due to SLE
Consider MPGN if low C3 > 2 mos
MPGN can also present after infection
MPGN may also  low C4
Diagnose by biopsy
TRAM-TRACKING 
McCrory, Peds In Review, 1983.

16. Considering DDX of PSGN
Normal C3:
IgA Nephropathy
Suspect if recurrent hematuria with URIs/Infections
Alport’s
+ Family History
HUS or HSP can present with gross hematuria
Post-viral GN
Boineau and Lewy Peds in Review 1989.

17. Treatment of AGN in General
Admit if HTN, edema, or signs of renal failure
Monitor/correct electrolyte anomalies
Treat HTN to avoid sequelae
Diuresis  loop diuretics like lasix
Fluid and salt restriction
Anti-hypertensives like the Ca-channel blockers
Simckes and Spitzer Peds in Review, 1995.

18. Treatment Specific to PSGN
Antibiotics to target Grp A Strep
Cultures often positive even if no symptoms, suggesting active infection
Treatment may  milder course of PSGN
Epidemics of Grp A Strep may warrant ppx to prevent PSGN, especially in underdeveloped societies
Unclear/controversial role for impact on OCD
Rodriguez-Iturbe and Musser, J Am Soc Nephrology, 2008

19. Prognosis and Sequelae
Good prognosis in children
CLOSE follow-up!
HTN resolves in ~ 1-2 weeks
C3 levels return to normal in ~ 6 weeks
Gross hematuria resolves in ~ 6 weeks
Microscopic hematuria resolves in ~ 1 year
Proteinuria resolves in ~ 6 months
Progression to renal dysfunction RARE
McCrory, Peds in Review 1983.

20. Take Home Points Urinalysis is KEY test to w/u discolored urine
UA with casts/dysmorphic RBCs = GN
HTN, edema, or renal dysfunction  admit
Poststrep GN = most common, due to characteristics of Strep and/or patient
Treat Strep infection and co-morbidities
Guarantee follow-up

21. Works Cited
Boineau and Lewy, “Evaluation of Hematuria in Children and Adolescents,” Pediatrics in Review, 1989.
Kurlan et al., “Streptococcal Infections and Exacerbations of Childhood Tics and OCD Symptoms: A Prospective Blinded Cohort Study,” Pediatrics 2008.
Massengill, “Hematuria,” Pediatrics in Review, 2008.
Rodriguez-Iturbe and Musser, “The Current State of Poststreptococcal Glomerulonephritis,” Journal of American Society of Nephrology, 2008.
Simckes and Spitzer, “Poststreptococcal Acute Glomerulonephritis,” Pediatrics in Review, 1995.
McCrory, “Glomerulonephritis,” Pediatrics in Review, 1983.