Hematuria

Gross hematuria:

Suspected if a red or brown color change of urine

Intermittent red or brown color urine a/w variety of clinical setting
Medications (phenazopyridine, microbid, NSAID)
Ingestion of beets or certain dyes
Metabolities
Myoglobinuria or hemoglobinuria

If pass clot, indicate lower urinary source

Work up

Centrifuge the specimen,

Supernatant be tested for heme (hemoglobin or myoglobin) with a urine dipstick.

Causes of heme-negative red urine
Medications Food dyes Metabolities
Beets (in selected
Doxorubicin Bile pigments
patients)
Chloroquine Blackberries Homogentisic acid
Deferoxamine Food coloring Melanin
Ibuprofen Methemoglobin
Iron sorbitol Porphyrin
Nitrofurantoin Tyrosinosis
Phenazopyridine Urates
Phenolphthalein
Rifampin
Approach to the patient with red
or brown urine
Microscopic hematuria:

Accidental finding from UA or urine dipstick

3 or more RBC/hpf in spun urine sediment.
No "safe" lower limit below which significant disease can be excluded
Often asymptomatic
The degree of hematuria does not correlate with the seriousness of the
underlying cause of the bleeding.
 Dx:

The urine sediment is the gold standard for the detection of microscopic hematuria

Dipsticks for heme are as sensitive as urine sediment examination,

but result in more false positive tests due to the following

 Semen is present in the urine after ejaculation

An alkaline urine with a pH greater than 9 or contamination with oxidizing agents used to
clean the perineum.
The presence of myoglobinuria.

A positive dipstick test must always be confirmed with microscopic examination of the urine
Major causes of hematuria by age and duration

Schematic representation of the major causes of hematuria in relation to the age at which they usually
occur (horizontal axis), transience or persistence (vertical axis), and frequency (blue implies more
frequent).
The evaluation should address the following three questions

1. Are there any clues from the history or physical examination that
suggest a particular diagnosis?

2. Does the hematuria represent glomerular or extraglomerular

bleeding?

3. Is the hematuria transient or persistent?

a three-tube test may also help to locate the
source of bleeding in selected cases.

Urethral: First 10-15 mL

Bladder: Final 10-30 mL
Upper urinary tract: Throughout
Goal is to quickly identify

1.Infection
2.Kidney stone
3.Malignant

Need immediate attention

History and Physical
History
 Abdominal or flank pain
􀂄 Dysuria, frequency, urgency
􀂄 Trauma
􀂄 Strenuous exercise
􀂄 Menstruation
􀂄 Recent URI/ sore throat
􀂄 Skin rashes/ skin infection
􀂄 Diarrhea (especially bloody)
􀂄 Joint pains/swellings
􀂄 Medications/toxins
􀂄 h/o sickle cell disease or sickle trait
Family history
Hematuria ,
Hearing loss,
HTN,
Stones,
Renal disease,
Dialysis or transplant,
Sickle cell trait *:
Coagulopathy,
Medication Hx
 Medication Hx
Mechanisms by Which Selected Drugs May Cause Hematuria
Interstitial nephritis
Papillary necrosis
Hemorrhagic cystitis
Urolithiasis
Captopril (Capoten)
Cephalosporins
Chlorothiazide (Diuril)
Ciprofloxacin (Cipro)
Furosemide (Lasix)
NSAIDs
Olsalazine (Dipentum)
Omeprazole (Prilosec)
Penicillins
Rifampin (Rifadin)
Silver sulfadiazine (Silvadene)
Trimethoprim-sulfamethoxazole (Bactrim, Septra
Acetylsalicylic acid (aspirin)
NSAIDs
Cyclophosphamide (Cytoxan)
Ifosfamide (Ifex)
Mitotane (Lysodren)
Carbonic anhydrase inhibitors
Dichlorphenamide (Daranide)
Indinavir (Crixivan)
Mirtazapine (Remeron)
Ritonavir (Norvir)
Triamterene (Dyrenium)
Physical Exam

􀂄 Vital sign: BP, T, HR

 Skin: Rashes, evidence or trauma, bruising
􀂄 Abdomen for masses, tenderness (flank, suprapubics), bruits
􀂄 CVS: irregular irregular
􀂄 Edema (especially periorbital)
􀂄 Joint erythema, swelling, warmth
􀂄 Paleness, jaundice
􀂄 Careful inspection of external genitalia
 Prostate
•If BP is elevated, further evaluation is immediately warranted
Physical Examination Findings and Associated Causes of
Hematuria
Physical examination finding
General (systemic) examination
Severe dehydration
Peripheral edema
Cardiovascular system
Myocardial infarction
Atrial fibrillation
Hypertension
Abdomen
Bruit
Genitourinary system
Enlarged prostate
Phimosis
Meatal stenosis
Cause of hematuria
Renal vein thrombosis
Nephrotic syndrome, vasculitis
 
Renal artery embolus or thrombus
Renal artery embolus or thrombus
Glomerulosclerosis with or without
proteinuria
 
Arteriovenous fistula
 
Urinary tract infection
Urinary tract infection
Urinary tract infection
 Clues from the history that point toward a specific diagnosis

1. Concurrent pyuria and dysuria, indicate UTI, may also occur with bladder malignancy.
2. A recent URI, raise the possibility of either post infectious glomerulonephritis or IgA
nephropathy
3. A positive family history of renal disease give suspicion of hereditary nephritis, polycystic
kidney disease, or sickle cell disease.
4. Unilateral flank pain radiating to the groin, suggesting ureteral obstruction due to a calculus
or blood clot, but can occasionally be seen with malignancy. Flank pain that is persistent or
recurrent can also occur in the rare loin pain hematuria syndrome.
5. Symptoms of prostatic obstruction in older men such as hesitancy and dribbling. The cellular
proliferation in BPH is associated with increased vascularity, and the new vessels can be fragile.
Clues from the history that point toward a specific diagnosis
6. Recent vigorous exercise or trauma
7. History of a bleeding disorder or bleeding from multiple sites due to
uncontrolled anticoagulant therapy.
8. Cyclic hematuria in women that is most prominent during and shortly after
menstruation, suggesting endometriosis of the urinary tract .
9. Medications that might cause nephritis (usually with other findings,
typically with renal insufficiency).
10. AA should be screened for sickle cell trait or disease, which can lead to
papillary necrosis and hematuria.
11. Travel or residence in areas endemic for Schistosoma hematobium .
12.Sterile pyuria with hematuria, which may occur with renal tuberculosis,
analgesic nephropathy and other interstitial diseases.
Glomerular or Extra Glomerular bleeding?
 Microscopic hematuria DDx
Glomerular

ARF
primary nephritis (post streptococcal glomerulonephritis, Ig A nephropathy,
Anti-GBM disease)
2nd nephritis(SLE, goodpasture’s syndrome, ANCA related vasculitis)
Alport’s syndrome (hereditary nephritis)
thin basement membrane nephropathy (benign familial hematuria)

•
 Microscopic hematuria DDx

non glomerular

Renal
malignancy
vascular disease
(malignant hypertension, AVM, nutcracker syndrome, renal vein thrombosis,
sickle cell trait/disease, papillary necrosis)
infection (pyelonephritis, TB, CMV, EBV)
hypercalciuria
hereditary disease (polycystic kidney disease, medullary sponge kidney)

Nonrenal
malignancy (prostate, ureter, bladder)
BPH
Nephrolithiasis
Coagulopathy
Trauma
Rare cause of Microscopic Hematuria

Arteriovenous malformations and fistulas 

Nutcracker syndrome 

Loin pain-hematuria syndrome

Arteriovenous malformations and fistulas —  An AV malformation (AVM)
or fistula of the urologic tract may be either congenital or acquired. The primary
presenting sign is gross hematuria, but high-output heart failure and
hypertension also may be seen . The latter is presumably due to activation of the
renin-angiotensin system resulting from ischemia distal to the AVM

Nutcracker syndrome — The nutcracker syndrome refers to compression of the

left renal vein between the aorta and proximal superior mesenteric artery.
Nutcracker syndrome can cause both microscopic and gross hematuria, primarily in
children (but also adults) in Asia . The hematuria is usually asymptomatic but may
be associated with left flank pain. Nutcracker syndrome has also been associated
with orthostatic proteinuria.

Loin pain-hematuria syndrome — The loin pain-hematuria syndrome is a poorly

defined disorder characterized by loin or flank pain that is often severe and
unrelenting, and hematuria with dysmorphic red cell features suggesting a
glomerular origin. Affected patients usually have normal kidney function.
 Extraglomerular vs Glomerular in UA
  Extraglomerular Glomerular
Color (if
Red or pink Red, smoky brown, or "Coca-Cola"
macroscopic)
Clots May be present Absent
Proteinuria <500 mg/day May be >500 mg/day
RBC morphology Normal Dysmorphic
RBC casts Absent May be present
 Findings on Microscopy

Erythrocytes of uniform character are

classified as isomorphic and suggest
hematuria of lower urinary tract origin.

Microscopic clots of clumped erythrocytes

in urine are also suggestive of lower urinary
tract bleeding.

                                      
FIGURE 1. Typical morphology of erythrocytes from a urine specimen revealing microscopic hematuria. (phase contrast microscopy, 3100 )
 Dysmorphic erythrocytes are characterized
by an irregular outer cell membrane and
suggest hematuria of glomerular origin.

Red blood cell casts are also associated with

a glomerular cause of hematuria.

FIGURE 2. Dysmorphic erythrocytes from a

urine specimen. These cells suggest a
glomerular cause of microscopic hematuria.
(phase contrast microscopy, 3 100)
Transient or persistent hematuria
Transient hematuria
Transient microscopic hematuria is a common problem in adults
Fever, infection, trauma, and exercise are potential causes
It is reasonable to repeat an abnormal urinalysis in a few days

Exception:

Malignancy risk in older patients with transient hematuria

In older patients, even transient hematuria carries an appreciable risk of

malignancy (assuming no evidence of glomerular bleeding)

The risks includes : age >50, smoker and Hx of analgesic abuse.

When persistent hematuria is essentially the only manifestation of
glomerular disease, one of three disorders is most likely

 IgA nephropathy, in which there is often gross hematuria, and

sometimes a positive family history but without any clear pattern of
autosomal inheritance

 Alport syndrome (hereditary nephritis), in which gross hematuria

can occur in association with a positive family history of renal failure,
and sometimes deafness or corneal abnormalities.

 Thin basement membrane nephropathy (also called thin basement

membrane disease or benign familial hematuria), in which gross
hematuria is unusual and the family history may be positive (with an
autonomic dominant pattern of inheritance) for microscopic
hematuria but not for renal failure .
Persistent hematuria

Underlying malignancy is greater in patients with persistent hematuria in

whom there is no obvious cause from the history

The primary underlying cancers are bladder, renal, and, much less often,
prostate
 Laboratory Tests (initial work up)

• UA and microscopy to determine the number and morphology of RBC, crystal and
casts
• Consider urine Cx
• CBC, PT, INR, electrolytes, kidney function
• Serum chemistries and serologic studies for glomerular causes of hematuria as directed
by the medical history
• Repeat UA in a few days

Further urologic evaluation is warranted if more than three RBC/phf are

found on at least two of three properly collected urine specimens or if high-
grade microscopic hematuria (more than 100 red blood cells per high-power
field) is found on a single urinalysis.17
Further Work up
• Glomerular causes:
 Consider a refer to nephrology for further evaluation and possible renal biopsy
Renal Biopsy

A biopsy is not usually performed for isolated glomerular

hematuria (i.e., no proteinuria or renal insufficiency,) since there is
no specific therapy for these conditions, unless the patient is
considering becoming a kidney donor

However, biopsy should be considered if there is evidence of

progressive disease as manifested by an elevation in the plasma
creatinine concentration, increasing protein excretion, or an
otherwise unexplained rise in blood pressure, even when the
values remain within the normal range
Further Work up
•Non-glomerular causes:

CT, renal US, and/or IVP: to search for lesions in the kidney, collecting
system, ureters, and bladder

Urine cytology: if increased risk for urothelial cancers

Consider a referral to urology for cystoscopy, especially for pt at risk of

malignancies
Radiologic and other tests for the evaluation of hematuria
Test Advantages Disadvantages
Excellent visualization of the May miss bladder lesions; can
Intravenous pyelogram (IVP) kidney, collecting system, and cause nephrotoxicity,
ureter idiosyncratic reactions (1/10,000)
Best way to examine the bladder,
Invasive, uncomfortable and
Cystoscopy which is not as well visualized by
expensive
IVP or ultrasound
If of good quality, as sensitive as
Less sensitive than IVP for ureter
Ultrasound IVP for renal lesions, with less
and bladder
morbidity and cost
The best test for examing the Invasive, not useful for
Retrograde pyelography ureters, can be combined with examining other parts of the
cystoscopy urinary collecting system
Sensitivity 67 percent, specificity
Useful only for cancer, mainly of
Urinary cytology 96 percent for uroepithelial
the bladder
cancer
Excellent for examining the renal
CT scan Expensive
parenchyma
Useful for gross hematuria when
other tests have not revealed the
Angiography Invasive, expensive
cause; the only good test for
vascular malformations
Follow up

The combination of negative radiologic examination(s)

( IVP, US, CT scan, cytology, and cystoscopy) is usually sufficient to exclude
malignancy in the urinary tract

However, approximately 1% of older pt with an initially negative evaluation will,

at 3 to 4 years, have a detectable urinary tract malignancy

Recommendation
Initial and then periodic urine cytology and UA should be performed in pt at
high risk for malignancy (at 6, 12, 24 and 36 months)
SCREENING FOR HEMATURIA

Not recommended
Initial Evaluation of Asymptomatic Microscopic Hematuria*
Reference:
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SO Am Fam Physician 2001 Mar 15;63(6):1145-54.U Mohr DN; Offord KP; Owen RA; Melton LJ 3d SO JAMA
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7.Evaluation of Asymptomatic Microscopic Hematuria in Adults. TIMOTHY R. THALLER, M.D
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8.Am Fam Physician 1989; 40(2):149-56, and Drugdex system. Englewood: Colo.: Micromedex, Inc., 1999.
Accessed Sept. 24, 1998.
9.Am Fam Physician 1989; 40(2):149-56, and Drugdex system. Englewood: Colo.: Micromedex, Inc., 1999.
Accessed Sept. 24, 1998.
10.Urothelial tumors of the urinary tract. In: Walsh PC, ed. Campbell's Urology. 7th ed. Philadelphia:
Saunders, 1998:2327-410.
11.A quick reference for urologist, AUA 2006
12.Up to date 2008
Thank you