1. Hematuria For the boards... Gital Karamchandani-Patel, MD 4/11/2017
One of the most common reasons that kids are referred to a nephrologist by their pediatrician
Gital Karamchandani-Patel, MD

2. Definition Macroscopic (gross) Hematuria Microscopic Hematuria
4/11/2017
Definition
Macroscopic (gross) Hematuria
any discolored urine visible to the human eye
Microscopic Hematuria
>5 RBC/hpf seen under microscope
50 RBC per microliter of unspun urine on a dipstick is also suggestive of hematuria
RBC seen on dipstick must be confirmed with an U/A
microscopic urine is done on fresh centrifuged urine sample

3. Hematuria What is your first step?
4/11/2017
Hematuria
Patient comes to your office complaining that their urine is reddish in color...
What is your first step?
Good H+P
Have to get a really good history
What kinds of questions are you going to ask?
ask about foods, drugs
ask about recent illnesses
ask about menstrual cycle
ask about dysuria, fever
ask about visual changes
ask about family history
Perform a good physical exam
what to look for on PE:
vitals (BP), edema, flank masses, bruising

4. Hematuria Is it really blood? Urine Dipstick Detects Hgb, myoglobin
4/11/2017
Hematuria
Is it really blood?
Urine Dipstick
Detects Hgb, myoglobin
Detects protein
In your office, you will have dipsticks readily available to you
Hemoglobin and myoglobin will produce the same color changes on the dipstick as intact RBCs via a peroxidase reaction
myoglobinuria may occur secondary to rhabdomyolysis (viral disease, crush injury, DIC)
false-positive test for blood can result from the presence of drugs such as ascorbic acid, sulfonamides, iron sorbitol, metronidazole, and nitrofurantoin
Best thing is to send U/A to the lab for a urinalysis
On your dipstick, you can also see if you have proteinuria. Isolated hematuria is something a PCP should be able to manage…when you have hematuria with proteinuria, you should refer to a nephrologist.

5. 4/11/2017
Hematuria
Urinalysis
Definitive for the presence of RBC

6. Hematuria Upper urinary tract Lower urinary tract calyx glomerulus
4/11/2017
Hematuria
Upper urinary tract
glomerulus
collecting tubules
interstitium
Lower urinary tract
calyx
pelvis
ureter
bladder
urethra
Once you have determined that it really is blood that you are dealing with, you need to try to figure out where it is coming from.
Blood cells can come from anywhere in the urinary tract.
The blood will look different depending on where it is coming from.

7. What PREP wants you to know...
4/11/2017
What PREP wants you to know...
Know the differential diagnosis of a child with gross hematuria

8. 4/11/2017
So to recap what our thinking process whenever we have someone present with gross hematuria to help us with our differential
get a good history
make sure it really is blood with a U/A
if it really is blood, do you have protein in your urine as well?
If there are no RBC, is there something in the history that could cause discolored urine?
-Myoglobin? PREP wants you to know that myoglobin can yield false + results for hematuria on urinalysis
-Hemoglobin?
-Diet/Drugs?
-Porphyria?

9. Glomerular Hematuria brown, tea colored urine proteinuria
4/11/2017
Glomerular Hematuria
brown, tea colored urine
proteinuria
deformed urinary RBCs
RBC casts
Proteinuria
RBC casts- RBC’s leak from the damaged glomerular walls
Proteinuria occurs bc protein leaks thru glomerular basement membrane
Deformed RBCs in the urine because they travel through the convoluted filtering system\
Urinary casts are cylindrical aggregations of particulate matter that form in the distal nephron, dislodge, and eventually pass into the urine. They form via precipitation of Tamm-Horsfall mucoprotein which is secreted by renal tubule cells, and sometimes also by albumin in conditions of proteinuria. Cast formation is pronounced in environments favoring protein denaturation and precipitation (low flow, concentrated salts, low pH).

10. Glomerular Hematuria RENAL MULTI-SYSTEM IgA nephropathy
4/11/2017
Glomerular Hematuria
RENAL
IgA nephropathy
Alport syndrome
Thin glomerular BM disease
Post infectious
MPGN
MULTI-SYSTEM
SLE nephritis
HSP nephritis
Wegener syndrome
Goodpasture syndrome
HUS
Sickle cell Disease
These will all be associated with proteinuria
will have brown/tea colored urine

11. W/u for Glomerular Hematuria
4/11/2017
W/u for Glomerular Hematuria
CBC
C3, C4
antistreptolysin-O titer, streptozyme titer
serum electrolytes, BUN, serum Cr, serum albumin
test for lupus
Hep B
antinuclear cytoplasmic antibody titer
Hep B because that can cause membranous nephropathy
ANCA for Wegeners

12. Extraglomerular Hematuria
4/11/2017
Extraglomerular Hematuria
Hematuria from lower urinary tract
terminal hematuria
blood clots
nl urinary RBCs
minimal proteinuria
Terminal hematuria is when the onset of gross hematuria occurs at the end of the urine stream

13. Extraglomerular Hematuria
4/11/2017
Extraglomerular Hematuria
UPPER URINARY TRACT
pyelonephritis
ATN
papillary necrosis
nephrocalcinosis
thrombosis
malformation
SCD
tumor
PCKD
LOWER URINARY TRACT
cystitis
urethritis
urolithiasis
trauma
coagulopathy
heavy excersise
UPJ obstruction
ureterocele
Munchausen, MBP

14. W/u for Extraglomerular Hematuria
4/11/2017
W/u for Extraglomerular Hematuria
serum creatinine
urine culture
sickle cell preparation in AA
urinary Ca/Cr ratio
C3,C4
U/S of kidneys/bladder to R/O polycystic kidney disease, tumor, ureteropelvic junction obstruction, and stones
Based on your history and physical you will determine what tests you want to order

15. 4/11/2017
Proteinuria
For the boards...

16. Proteinuria Occurs in 10% of kids 8-15 yrs differentiate between
4/11/2017
Proteinuria
Occurs in 10% of kids 8-15 yrs
differentiate between
renal disease
transient
benign

17. Proteinuria Dipstick detects mostly ALBUMIN negative (0 mg/dL)
4/11/2017
Proteinuria
Dipstick detects mostly ALBUMIN
negative (0 mg/dL)
trace (10-20 mg/dL)
1+ (30 mg/dL)
2+ (100 mg/dL)
3+ (300 mg/dL)
4+ ( mg/dL)
False negatives may also occur if the protein in the urine is composed mainly globulins or Bence-Jones Proteins because the reagent on the test strips, Bromphenol blue, is highly specific for albumin

18. 4/11/2017
Orthostatic proteinuria
Transient proteinuria
caused be temp >101oF
excersise
dehydration
cold exposure
CHF
seizure
stress
Glomerular proteinuria is usually due to loss of albumin
tubular proteinuria is usually due to loss of other proteins

19. Proteinuria What is your next step?
4/11/2017
Proteinuria
A child comes into your office for a routine visit
Screening urine dipstick reveals 1+ protein
What is your next step?

20. Proteinuria R/O benign conditions sg >1.020 pH >7.5 mucoproteins
4/11/2017
Proteinuria
R/O benign conditions
sg >1.020
pH >7.5
mucoproteins
acute illness
Acute illnesses, excersise
Once you have determined that none of these are what caused the + dipstick, you can move on to further evaluation.

21. Proteinuria Next step is to determine if this is transient or fixed
4/11/2017
Proteinuria
Next step is to determine if this is transient or fixed
R/O orthostatic proteinuria
first am U/A
W/u for persistent fixed proteinuria
alb, C3, 24 hr urine protein
Pr/Cr ratio
W/u for glomerular hematuria if + RBCs

22. Let’s see who has been paying attention...
4/11/2017
Quiz Time
Let’s see who has been paying attention...

23. 4/11/2017
Quiz time #1
10 yr old boy coming in for school physical. Found to have 30 RBC/hpf on microscopic analysis.
Fam Hx reveals uncle used to have “blood in his urine”
What is your diagnosis?
What is the diagnosis.
You have something familial going on…
Lets think about our differential for familial causes of hematuria

24. Quiz time #1 Familial Causes of Hematuria Polycystic kidney disease
4/11/2017
Quiz time #1
Familial Causes of Hematuria
Polycystic kidney disease
Thin basement membrane disease
Alport syndrome (hereditary nephritis with deafness)
Hypercalciuria with family history of nephrolithiasis
Sickle Cell
A family history of autosomal dominant polycystic kidney disease demands that this disease be ruled out by renal U/S.
A family history of hematuria without renal failure may be seen with thin basement membrane disease.
A family history of hematuria, chronic renal failure, dialysis, or renal transplantation with bilateral deafness at an early age and ocular abnormalities strongly suggests Alport syndrome. An audiogram is indicated for children suspected of having Alport syndrome because high-tone hearing loss may not be apparent on the initial examination.
A family history of nephrolithiasis raises the diagnostic possibility of nephrolithiasis or hypercalciuria.
Sickle cell disease or sickle cell trait in the patient's family may suggest this diagnosis
a screening urinalysis in available first-degree relatives is an important test

25. Quiz time #2 Gross hematuria following a URI C3 is wnl
4/11/2017
Quiz time #2
Gross hematuria following a URI
C3 is wnl
What is your diagnosis?
What two things could it be?
Post strep
IgA nephropathy
how can you tell the difference?

26. IgA Nephropathy (Berger’s Disease)
4/11/2017
IgA Nephropathy (Berger’s Disease)
IgA deposits seen on renal biopsy
nl C3
elevated IgA in 15%
often hypertensive
need long-term f/u
Assoc with viral URI or AGE
20-30% of children who have this will have progressive disease years down the road

27. 4/11/2017
Quiz time #3
This kid was in your office 2 weeks ago. Mom is calling and saying his urine looks like coca-cola.
What is your diagnosis?
This boy came into your office two weeks ago. His mom is calling the office saying is urine is tea colored.
What is this boy’s diagnosis? impetigo
What is it caused by? nephritogenic strain of GAS
How do you diagnose it? Streptozyme (for skin), (ASO for throat)
could this have been prevented with appropriate abx? NO
What do you treat it with?
What would you expect his C3 levels to be? LOW
what happens to C3 level after 2 months? Returns to nl

28. Acute Post-Infectious Glomerulonephritis
4/11/2017
Acute Post-Infectious Glomerulonephritis
Caused by nephritogenic GAS infections of the pharynx or skin
Most children recover complete renal function
C3 levels LOW initially, then return to NL after 6-8 wks
may have BP, proteinuria, hematuria for up to 3 mos after initial presentation

29. Quiz time #4 3 yr old F with diarrhea
4/11/2017
Quiz time #4
3 yr old F with diarrhea
6 days later develops a rash, abdominal pain
on PE, you note pallor and purpura

30. Quiz time #4 What is your diagnosis? 4/11/2017
You get a CBC and peripheral smear reveals fragmented RBCs

31. Hemolytic-Uremic Syndrome
4/11/2017
Hemolytic-Uremic Syndrome
MCC of ARF in children
Caused by shiga toxin producing E.coli O157:H7
HUS is most common in kids less than 4yrs
preceded by AGE with fever, vomiting, bloody diarrhea
E.coli transmitted by undercooked meat, unpasteurized milk
this organism has a verotoxin which is absorbed by the intestine and initiate endothelial cell injury
microangiopathic hemolytic anemia

32. Quiz time #5 Infant comes in with hematuria h/o constipation
4/11/2017
Quiz time #5
Infant comes in with hematuria
h/o constipation
h/o TEF repair
What is your diagnosis?
What is your diagnosis?
VATER association
V vertebral anomalies
A anal atresia
TE TEF
R radial limb anomalies
What is your next study?
Chromosomes for genetic syndrome should be ruled out

33. VATER association V vertebral anomalies A anal atresia T E
4/11/2017
VATER association
V vertebral anomalies
A anal atresia T E
R radial limb anomalies
TEF

34. 4/11/2017
Quiz time #6
14yo female with hematuria
More “tired” lately

35. Quiz time #6 What is your diagnosis? What labs will you order?
4/11/2017
Quiz time #6
What is your diagnosis?
What labs will you order?

36. SLE nephritis C3 and C4 will be LOW
4/11/2017
SLE nephritis
C3 and C4 will be LOW
Sometimes will only manifest as kidney disease
WHO staging of nephritis
Class IV is the most common and most severe form of nephritis

37. Quiz time #7 11 yr old boy with gross hematuria, edema.
4/11/2017
Quiz time #7
11 yr old boy with gross hematuria, edema.
Initial labs reveal LOW C3 and C4
What is your diagnosis?
How do you make definitive dx?
You know it is something glomerular because of hematuria and proteinuria. Lab work helps you.

38. Membranoproliferative Glomerulonephritis
4/11/2017
Membranoproliferative Glomerulonephritis
MPGN is the MCC of chronic glomerulonephritis in children
renal biopsy confirms dx

39. Confused about complement?
What three conditions cause hypocomplementemia?
P post infectious GN
M membrano proliferative GN
S SLE

40. 4/11/2017
Quiz time #8
last one!
It is 10pm. You are the intern on call for purple. A 5th floor nurse pages you to tell you that ortho has just consulted you on one of their patients for hematuria.

41. Quiz time #8
You look through the chart and the all you can decipher is that she was in a car crash 2 weeks ago.
You go to examine her and note she is in a full body cast, o/w NAD and afebrile.
What is the one test you will order before you go back to your call room?

42. Quiz time #8 Answer: Urine Ca/Cr ratio!!
urinary calcium:urinary creatinine ratio of > 0.21
24-hour urinary calcium excretion of >4 mg/kg

43. Hypercalciuria Idiopathic 30% Immobilization Hyperparathyroidism
4/11/2017
Hypercalciuria
Idiopathic 30%
15% go on to have renal stones
Immobilization
Hyperparathyroidism
Furosemide
Vit D intoxication
Renal ultrasonography and plain abdominal radiography are helpful in ruling out the presence of nephrocalcinosis or nephrolithiasis.
The finding of hypercalciuria in a child who has hematuria should not exclude consideration of other etiologies of hematuria

44. Thank you for your attention!

46. 4/11/2017
PREP specs
Plan the evaluation of hematuria in a child with sickle cell disease.

47. 4/11/2017
PREP 2005 #70
A previously healthy 10 yr old AA boy reports a 2 day history of back pain and gross hematuria. There is no history of trauma or passed kidney stones. His vital signs are normal, and PE reveals R CVA tenderness. His older brother has several similar episodes when he was younger, as did his mother when she was a child.

48. 4/11/2017
PREP 2005 #70
You suspect that this boy has sickle cell trait and papillary necrosis.
Of the following, the BEST test to confirm the diagnosis is:
A. abdominal xray
B. CT
C. intravenous pyelography
D. renal scintigraphy
E. renal U/S
Ab x-ray will not help you look for papillary necrosis
CT may show papillary necrosis
IVP
renal scintigraphy is done when obstruction is present, show tracer uptake of functioning kidney
renal U/S will show vague changes in the medulla but not specific for papillary necrosis

49. PREP 2005 #70 Correct Answer: C 4/11/2017
Hematuria results from microthrombosis secondary to sickling
they want you to know that IVP is the best test to look for papillary necrosis
the difference is hematuria and PAIN