A 55-year-old male presents with blood in his urine. Urinalysis shows 2+ blood and 2 red blood cells per high-powered field. The patient's history of smoking increases his risk for urinary tract malignancy. The appropriate initial step is to repeat the urinalysis and urine microscopic to confirm if the patient meets the criteria for microscopic hematuria of 3 or more red blood cells per high-powered field on two properly collected urine specimens. Further evaluation including imaging of the urinary tract should be considered given the patient's risk factors.

1. Approach to Hematuria
in Primary Care
Hasan Ismail, MD
1

2. DEFINITIONS
• GROSS HEMATURIA : The presence of enough
blood in a urine sample to be visible to the naked
eye
• MICROSCOPIC HEMATURIA : The presence of 3 or
more RBCs per HPF on two or more properly
collected urinalyses
(AMH found in 9–18% of adults)
2

3. 3

4. Case Scenario
• A 55-year-old male presents to your office for
evaluation of blood in his urine.
• It turns out that the urinalysis showed 2+
blood on urine dipstick and 2 RBC/hp .
• The remainder o the urinalysis and
microscopic examination was normal.
4

5. After an appropriate history and physical
examination, your first step in the evaluation of this
urine abnormality is to:
A) Repeat the urinalysis and microscopic examination.
B) Obtain urine or culture.
C) Order a renal ultrasound.
D) Order a C scan o the abdomen.
E) Order an intravenous pyelogram (IVP).
5

6. • The correct answer is “A.”
• According to the urinalysis, there is a small amount
of blood in your patient’s urine, but the number o
RBCs is actually normal (< 3 RBC/hp ).
• Your first step should be to repeat the urinalysis
and urine microscopic examination to determine if
this patient actually meets the criteria or
microscopic hematuria (≥ 3 RBC/hp on two of the
three properly collected urine specimens,
according to the American Urological Association).
6

7. • A urine culture may prove useful later in the
evaluation process but is not necessary now.
• Likewise, ordering imaging studies is
premature because the diagnosis of
microscopic hematuria has not been made.
7

8. • Further history reveals that he smokes one to two
packs of cigarettes per day.
• He has a normal blood pressure and the
remainder o the physical examination is
unrevealing.
• On two urine samples, you find microscopic
hematuria, with a positive dipstick and 5 RBC/hp .
• The rest of the urinalysis is normal, and there are
no red cell casts.
8

9. In your evaluation o this patient, you include all of
the following tests EXCEPT:
A) Urine cytology.
B) CBC.
C) Serum creatinine.
D) CT scan of the abdomen and pelvis with
particular note of the kidneys.
E) Renal biopsy.
9

10. • The correct answer is “E.”
• In most cases of microscopic hematuria, renal
biopsy is not indicated.
• However, if an intrinsic renal cause of
hematuria is suspected, renal biopsy may
prove necessary.
10

11. Intrinsic renal disease is more likely if there is
proteinuria, hypertension, elevated serum
creatinine, or an active urinary sediment (e.g.,
nephritic, dysmorphic red cells, red cell casts).
11

12. • There is no completely standardized evaluation
of microscopic hematuria, and
recommendations vary depending on the author.
• However, the recommendations always include
serum creatinine and usually include CBC,
coagulation studies, and serum chemistries.
• Depending on the patient’s age, further studies
may be indicated
12

13. • For patients older than 40 years, you should
consider studies to evaluate or urinary tract
cancers.
• Urine cytology has low sensitivity but high
specificity or bladder cancer and may be quite
useful in conjunction with cystoscopy.
• Imaging of the urinary system is an absolute
requirement in the work-up o microscopic
hematuria in older patients (generally, those
over age 40 years).
13

14. • CT scan appears to have the greatest sensitivity
or detecting masses, but ultrasound, IVP, or the
combination of the two may also be employed.
• Cystoscopy should be considered if the CT scan
is normal since CT is poor at visualizing bladder
abnormalities.
14

15. The US Preventive Services Task Force
recommends which o the following screening
strategies or detecting microscopic hematuria?
A) Annual urinalysis af er age 50.
B) Urinalysis every 2 years af er age 50.
C) Annual urinalysis af er age 65.
D) Annual urinalysis in all high-risk patients older
than 65 years.
E) No screening at any age.
15

16. • The correct answer is “E.”
• The USPS F recommends against routine
screening or microscopic hematuria to detect
urinary tract cancers.
• In one-time urine specimens in healthy adults,
the presence of abnormal numbers o RBCs (≥ 3
RBCs/hp ) can be as high as 39%.
• In up to 70% of patients, even after imaging of
the upper and lower urinary tract, the source of
microscopic hematuria cannot be found. 16

17. • In a low-risk population, the false-positive rate of
microscopic hematuria found on urinalysis would
be unacceptably high.
• Also, there is no evidence that early detection of
urinary tract cancers through screening urinalysis
improves prognosis.
17

18. History
• Transient vs. persistent
hematuria
• Fevers
• Pain
• Medications,
• Trauma
• Pyuria
• Dysuria
• blood clots
18
• Lower urinary tract symptoms
• Recent URI (postinfectious
glomerulonephritis/IgA
nephropathy) or sexual activity
• Personal/family history of
renal disease
• Malignancy
• Bleeding disorders
• Occupational exposures
• Travel hx
Ann Int Med 2016;164:488
JAMA 2016;315:2726
NEJM 2003;348:2330

19. • Medications & food associated with red urine:
Rifampin, phenazopyridine, iron sorbitol,
nitrofurantoin, chloroquine; rarely beets,
blackberry, rhubarb, food coloring
• Medications associated with Hematuria:
Aminoglycosides, amitriptyline, analgesics,
anticonvulsants, ASA, diuretics, OCPs, penicillins
(extended spectrum), warfarin
19
AFP 2006;73:1748

20. Etiologies
Hematuria is divided into
1. Renal (Glomerular)
2. Renal (nonglomerular)
3. Urologic
20

21. 21
Renal
(Glomerular)
Renal (Non-
glomerular)
Urologic
Significant
proteinuria
Significant
proteinuria
NO
proteinuria
Erythrocyte
casts, and
dysmorphic
rbcs
NO
erythrocyte
casts, and
dysmorphic
rbcs
NO
erythrocyte
casts, and
dysmorphic
rbcs

23. Renal (Glomerular) causes
• Diabetic Npehropathy
• Amyloidosis
• Membranoproliferative glomerulonephritis (MPGN)
• Post-Streptococcal glomerulonephritis
• Small vessel Vasculitis
• Anti–glomerular basement membrane (GBM) disease
23

24. Renal (nonglomerular) causes
• PKD
• RCC
• Ruptured hemangioma
• AVM
• Nutcracker syndrome
• Infarct/papillary necrosis
• TB
• Sarcoid
24

25. Urologic causes
• BPH
• Infection (UTI, pyelonephritis, prostatitis, urethritis,
viral infection)
• Sickle cell
• Stones
• GU malignancy
• Hydronephrosis
• VU reflux
• Fistula
• Hemorrhagic cystitis (cyclophosphamide)
• Recent urologic procedure 25

26. Other Causes
• Exercise ("march hemoglobinuria")
• Trauma
• Foley
• Endometriosis (cyclic hematuria)
• Sex
• DRE
26

27. False +
• Gyn source
• Supratherapeutic anticoagulation
• Semen
• Myoglubinuria
• pH >9
• Dilute urine (osmotic cell lysis)
27

28. AUA Risk Factors for Malignancy
• Age >35
• Tobacco use
• Analgesic abuse (phenacetin)
• Pelvic XRT
• Alkylating agents (i.e., cyclophosphamide),
• Occupational (dyes, benzene. aromatic amines).
• Irriative voiding sx/chronic cystitis
• Gross hematuria
• Repeated UTIs
• Chronic indwelling foreign body 28

29. Evaluation of AMH
After microscopic hematuria has been identified
(2 of 3 urine samples with 3 or more RBC/hpf),
the American Urological Association (AUA)
recommends the following evaluation:
29

30. • Infection identified  treat with antibiotics
and repeat urinalysis after 6 weeks
• RBC casts, proteinuria, or elevated creatinine 
begin evaluation for glomerulonephritis and
consider referral to a nephrologist
30

31. • No infection or primary renal disease identified in
first 2 steps 
- CT scan (contrast ?)
- bladder cystoscopy (if at risk for bladder cancer
based on environmental exposures and/or age >
40)
31

32. If entire thorough diagnostic
evaluation negative  follow-
up urinalysis, urine cytology,
blood pressure, and serum
creatinine every 6-12 months
32

33. Cytology ?
• Cannot r/o bladder Ca (Se 40–76%)
• But ⊕ cytology  diagnostic of urothelial Cancer
• NOT recommended as part of routine evaluation
of AMH
• May be useful if workup otherwise ⊖
33

34. Take home message
• Hematuria in adults should always be
evaluated.
• If no source is found on a thorough initial
workup, patients should be followed for at
least 3 years to monitor for an underlying
condition.
• In every case of a first-time microscopic
hematuria, a repeat urinalysis with
microscopy is required at 6-week interval
before any other management is done.
34

35. 35

36. References
• Cohen RA, Brown RS. Microscopic hematuria. N Engl]
Med. 2003;348:2330-2338.
• Davis RJ, Jones S, Barocas DA, et al. Diagnosis,
evaluation and follow-up of asymptomatic
microhematuria (AMH) in adults: AUA guideline. 2012.
American Urological Association.
• Grossfeld GD, Litwin MS, Wolf JS, et al. Evaluation of
asymptomatic microscopic hematuria in adults: the
American Urological Association best practice policy-
part I: definition, detection, prevalence, and etiology.
Urology. 2001;57( 4):599-603.
• O'Connor OJ, McSweeney SE, Maher MM. Imaging of
hematuria. Radiol Clin North Am. 2008;46:113.
36

37. • A 60-year-old man with past medical history
of BPH presents to you with gross hematuria
for 1 day.
• He states this has never happened before and
denies strenuous exercise.
• Upon further questioning he does reveal that
2 days ago he had a bladder catheterization to
evaluate his postvoid residual.
• He denies smoking, family history of cancers,
or chemical exposures.
• Which of the following is the most appropriate
management at this time? 37

38. A. Counsel the patient on the high likelihood of gross
hematuria after a urologic procedure and that this
will likely subside. Let him know no test is required
today.
B. Do a urine dipstick first. If positive then proceed
to urinalysis with microscopy and have the patient
return in a few weeks for a repeat UA with
microscopy.
C. Discuss with the patient the high likelihood of
malignancy with gross hematuria especially given his
age and past history and recommend imaging upper
and lower urinary tracts.
D. Tell him that he likely needs urine cytology today
to rule out malignancy.
38

39. • A 54-year-old postmenopausal woman with
past medical history of hypertension is
incidentally found to have significant
microscopic hematuria on a UA that was done
as part of her annual hypertension laboratory
tests.
• She denies dysuria, gross hematuria, fevers,
chills, and nausea/vomiting.
• Her physical examination is negative for
suprapubic tenderness and flank pain.
• What would be the next best step in the
management of this patient?
39

40. A. Repeat UA with microscopy in 3 months at her next
follow-up visit for hypertension.
B. Perform a urine culture and if positive, treat
immediately. Repeat UA posttreatment.
C. Order renal function testing to rule out medical
renal disease as an etiology.
D. Repeat UA with microscopy in 6 weeks.
40

41. • A 65-year-old man with past medical history of
hypertension, coronary artery disease, chronic kidney
disease (CKD), and a pacemaker presents to your office
with complaint of “dark urine” for many weeks now.
• He states he has been evaluated by several other
physicians who had done "several tests“ that all came
back negative.
• He states he has never had any imaging done and would
like you to "take a look at what is going on in there”
• Upon accessing his medical records you see that he has
already had several UA with microscopy that were all
positive for microscopic hematuria, renal function testing,
which is significant for elevated BUN and creatinine and
decreased GFR, and negative urine cultures.
• At this time, what would be the most appropriate imaging
modality and management for this patient? 41

42. A. Counsel the patient against imaging at this time as
any imaging may worsen his CKD.
B. Order magnetic resonance urography (MRU) as
the patient is unable to undergo CT urography given
his renal insufficiency, along with an urgent urology
referral.
C. Order a combined renal ultrasound and
retrograde pyelogram for maximum visualization of
upper urinary tract, along with an urgent urology
referral.
D. Order urine cytology and urine markers as these
are the least invasive test of choice at this time.
42