1. Hematuria

2. Epidemiology Hematuria
Defn- presence of excessive numbers of red blood cells (RBCs) in the urine
macroscopic-- gross
microscopic-- visible with the aid of a microscope only

3. Epidemiology Hematuria
Normal patients can excrete 104 to 105 RBC in a 12-hr period
Corresponds to several RBCs in the sediment of a randomly collected, centrifuged specimen under high power magnification
therefore hematuria is >4 RBC/hpf of urine sediment

4. Epidemiology Hematuria Children
prevalence of microheme approximately 4%
majority have normal UAs on f/u and do not develop urinary tract pathology
therefore isolated microheme in children does not require extensive evaluation

5. Epidemiology Hematuria recall
dipsticks detect globin pigments-- not RBCs, therefore a positive dipstick must be validated by microscopy
r/o myoglobinuria (rhabdomyolysis) and severe hemolysis

6. Hematuria Where did the RBCs come from? Glomerulus Tubule bladder
urethra
ureter
penis
vagina
prostate
rectum

7. Hematuria Glomerulus Tubule Where did the RBCs come from? ureter
Proliferative GN
Primary
IgA
Post-infx GN
MPGN
Crescentic GN
Fibrillary GN
Secondary
HSP
SLE
Anti-GBM (Good pasture's)
Systemic Vasculitis
Chronic Bacteremia
Cryoglobulinemia
Hepatitis B/C
Non-Proliferative
Minimal Change
FSGS
Membranous
HUS
Familial Glomerular Dz
Alport's syndrome
Thin basement membrane disease
Fabry disease
Nail-Patella
ureter
prostate

8. Hematuria - Where did the RBCs come from?
Glomerulus
Tubule
Renal Causes-- Non-Glomerular
Familial
ADPKD
Medullary Cystic Disease
Medullary Sponge Kidney
Papillary Necrosis
Analgesic abuse
Sickle Cell Disease and Trait
Renal TB DM
Obstructive uropathy
Alcoholism
Anklosing Spondyltis
Hydronephrosis
Drugs
interstitial nephritis
Trauma
Renal Contusion or laceration
Exercise hematuria
Neoplasms
renal cell cancer
Wilms tumor
benign cysts
tuberous sclerosis
multiple myeloma
Vascular
renal infarct
renal vein thrombosis
malignant hypertension
AVM
Loin-pain hematuria
Metabolic
Hypercalcuria
Hyperoxaluria
Hyperuricosuria
Cystinuria
ureter
prostate

9. Hematuria-- non renal Glomerulus Tubule bladder urethra ureter penis
Calculi
ureter, bladder, prostate
Neoplasms
TCC
prostate Ca/BPH
squamous cell
Infections
cystitis, prostatitis, urethritis TB
Schistosomiasis
Drugs
cyclophosphamide
anticoagulants
Trauma
Contusion/laceration
exercise induced hematuria
foreign body
decompression of severely
distended bladder
Genital or anal bleeding
bladder
urethra
ureter
penis
vagina
prostate
rectum

10. Hematuria History frequency/dysuria - UTI
hesitancy, weak stream, and dribbling - bladder obstruction 2nd stone/tumor/ prostate
colicky flank pain that radiates to groin-- stone or renal papillary necrosis
arthralgia/arthritis/rash - systemic inflammatory disorder-- HSP, SLE, or other systemic vasculitis
s/p bloody diarrhea -- think HUS

11. Hematuria
History
1-2 weeks s/p pharyngitis/skin infection - post-strep GN
family h/o deafness/hematuria/renal failure -Alport's syndrome (hereditary nephritis)
transient hematuria s/p exertion
foreign travel--Schistosoma haematobium

12. Hematuria Type of bleeding Color Clots
brown or cola-colored-- usually kidney
pink or red usually suggests extra-renal
Clots
usually indicated a non-renal source

13. Hematuria Physical Exam
Vitals-- hypertension-- esp new c/w renal pathology
HEENT-
CV-
Resp-
Abd--
Ext-- edema more c/w renal pathology
arthritis-- SLE/inflammatory d/o
GU-- vaginal/rectal source of blood. BPH?
Skin-- rash

14. Hematuria UA
proteinuria accompanying hematuria is glomerular disease until proven otherwise
don’t send to Urology to r/o stones/TCC
Potential error-- HgB is a protein -- nl Hgb (12grams/dl), therefore hematuria (if hemolyzed) can easily cause measurable proteinuria
Pyuria-- frequently seen with UTI/STDs

15. Hematuria Urine microscopy Crystals
Casts-- presence also points toward renal pathology
dysmorphic RBCs
presence confirms glomerular disease, absence has no diagnostic implications

16. Hematuria Glomerular Labs Chem 7 serum complement
low-- MPGN, SLE, cryoglobulinemia
ASO and anti-Dnase B
HepBsAG, anti-HC
ANA
Other (depending upon clinical scenario)
anti-gbm-- pulm hemorr or rpgn
anca- s/s of vasculitis
cryoglobulins
pt/ptt
sickle screen

17. Hematuria Glomerular Additional studies/info
r/o hereditary nephropathy
Alport’s, Thin Basement Membrane Disease (AKA benign familial hematuria), and ADPKD
screen all available family members with UA
if Alport’s suspected
audiologic examination
anterior lenticonus, yellowish perimacular flecks

18. Hematuria Glomerular Biopsy considered on a case by case basis
risks-- 1/ /5000 risk of death, defining disease often will NOT result in a change in therapy
avoid if s/p recent sore throat, acute nephritis, and low complements
usually performed if associated with renal insufficiency, proteinuria, or low complement

19. Hematuria Nonglomerular Hematuria
If pyuria-
urine culture
STD screen
African-American
consider SICKLE CELL TRAIT OR DISEASE
h/o cytoxan therapy
hemorrhagic cystitis

20. Hematuria Non-glomerular Hematuria
If initial evaluation unremarkable:
renal US
KUB
and >40yo, consider urology referral
urine cytology
cystoscopy

21. Initial Evaluation Rule out obvious benign causes Infection Activity
Irritative sx’s or WBCs on U/A  Culture
Treat appropriately
Men – 30 days of quinolone & consider GU evaluation
Repeat U/A in 6 weeks
Activity
Vigorous exercise, sex, virus, trauma, menses
Repeat U/A 48+ hours after cessation
External lesions
Examine penis or perineum & vagina

22. Initial Evaluation Rule out nephrologic hematuria Proteinuria
1+ on dipstick, > mg on 24 hr urine
RBC Casts
Pathognomonic for glomerular bleeding
Dysmorphic RBCs
Variation in size & shape, irregular/distorted outline
Predominance suggest glomerular origin
Renal insufficiency
New rise in creatinine

23. General Evaluation Imaging upper tracts Cytology Cystoscopy
Modify based on risk factors

24. Imaging Looking for: Renal tumors Collecting system tumors Stones
Other – UPJO, infection

25. Imaging IVP Ultrasound Old standard Misses smaller stones and masses
Misses smaller solid masses
Operator & body habitus dependent
OK for screening low-risk pts
Good in combo with retrograde pyelograms for contrast allergic pts.

26. Imaging CT Current “Gold Standard” “Hematuria protocol”
Stones: 94-99% sensitive
Masses: excellent down to ~1 cm
“Hematuria protocol”
No oral or rectal contrast
Non-contrast spiral CT full GU tract
Renal dedicated IV contrast view(s)
Early (arterial) and nephrographic
Excretory phase of full GU tract

27. Imaging CT How to order 3 separate orders
CT, ABDOMEN WO/W CONTRAST
CT, PELVIS WO/W CONTRAST
CT, KIDNEYS W/WO CONTRAST
“Hematuria protocol” in comments at NNMC
?? CHCS order line coming soon ??

28. Imaging Retrograde pyelogram Collecting system anatomy only
In conjunction with non-contrast CT or ultrasound for contrast allergic patients
To confirm abnormality on initial imaging
Performed at the the time of clinic cystoscopy
!! Best to have imaging results prior to cystoscopy

29. Cytology Examination of exfoliated cells in the urine
Looking for malignant cells
Sensitivity for urothelial cancer
Excellent (90+%) for high-grade
Poor (40%) for low-grade
“Reactive” cells often suggest a stone
“Atypical” or “Suspicious”
Only 15% truly malignant

30. Cytology How to order Lab CYTOLOGIC NON-GYN
# Container Specimen Description Frozen
= ====== =================== ======
A Voided urine NO
B Voided urine NO
C Voided urine NO

31. Cytology Patient instructions Well hydrated & active
Not first morning void
Fill container
Refrigerate immediately
Turn in <24 hrs

32. Cystoscopy Complete visualization of the bladder mucosa
Anatomy of urethra, prostate, ureteral orifices

33. Low-Risk Evaluation No risk factors CT Either cystoscopy or cytology
Stop after non-contrast phase if cause found
Ultrasound also reasonable
Either cystoscopy or cytology

34. Benign Hematuria Benign/Isolated/Idiopathic Hematuria
Negative full workup
~2/3 have mild structural abnormality if biopsied
At risk for mild nephropathy with low risk of progression
<3% have missed malignancy

35. Follow-Up Follow-Up Protocol Annual Modify based on risk Urinalysis
Cytology x1 BP
Start in 6 months, continue for three years
Modify based on risk

36. Follow-Up Re-evaluate if: Nephrology Evaluation
Significant increase in hematuria
Ex now RBC/HPF
Abnormal urinary cytology
Irritative voiding symptoms develop in the absence of infection
Nephrology Evaluation
HTN, Proteinuria, RBC Casts, Dysmorphic RBCs

37. Take Home Messages Dx: 3 RBC/HPF, 2/3 samples, properly collected
R/o benign & nephrologic causes
Begin w/u with CT & cytology x3
Consult Urology
Cystoscopy
F/u yearly for 3 years with Hx, BP, U/A, cytology

38. Hematuria Pearls Hematuria (<4rbc/phpf) is normal
Strenuous exercise can induce hematuria
Hematuria accompanied by proteinuria usually represents a renal source
Only RBC casts or dysmorphic RBCs reliably localize hematuria to the kidney
Microheme is the most common presentation of sickle trait