An approach to hematuria (unedited)

1. Approach to Hematuria
Sushil Gyawali
MS Resident
Urology and Kidney Transplant Unit

2. Hematuria
• Hematuria: Greek words haima (blood) and ouron (urine) to refer to
the presence of blood in the urine.
• Hematuria is defined as the presence of at least 5 red blood cells/HPF
in 3 of 3 consecutive centrifuged specimens obtained at least 1 week
apart.
• A diagnosis of hematuria is confirmed by demonstration of red blood
cells in the urinary sediment as shown by qualitative and quantitative
microscopy

3. Types
• Gross or Microscopic.
-Microscopic hematuria refers to the detection of blood on urinalysis
or urine microscopy.
- Gross/macroscopic: presence of red or brown urine. The color
change does not necessarily reflect the degree of blood loss, since as
little as 1 mL of blood per liter of urine can induce a visible color
change.
• Intermittent or persistent.
• Painful or Painless
-Asymptomatic or symptomatic and may be associated with other
urinary tract abnormalities

4. According to Timing (when it occurs during urination):
• Early (initial) haematuria: Urethral origin, distal to external Sphincter
• Terminal haematuria: Bladder neck or prostate origin
• Diffuse (total) haematuria: Source is in the bladder or upper urinary
tract

5. Pathophysiology
• Glomerular
• Non glomerular
• False hematuria: Discolouration of urine from pigments such as food
colouring and myoglobin.
• Silent hematuria is due to tumours of kidney or bladder unless proved
otherwise.

6. Etiology
• Glomerular
• TubuloInterstitial
• Uroepithelium
• Vascular
• Systemic diseases
• Infections

8. Glomerular causes
• Thin basement membrane disease (benign familial hematuria)
• Alport Syndrome
• IgA nephropathy
• HUS
• Postinfectious glomerulonephritis
• Membranoproliferative glomerulonephritis
• Lupus Nephritis
• Henoch- Schonlein Purpura

9. Tubulointerstitial disease
• Papillary necrosis
• Interstitial nephritis
• Analgesic nephropathy
• Nephrolithiasis
• Reflux nephropathy
• Hydronephrosis
• Ureteropelvic junction obstruction

10. Uroepithelium
• Malignancy
• Trauma
• Papillary Necrosis
• Cystitis/Urethritis/Prostatitis (UTI)
• Parasitic Diseases (Schistosomiasis)
• Stones

11. Vascular
• Arterial emboli or thrombosis
• Arteriovenous fistulae
• Renal vein thrombosis
• Renal Infarction
• Malignant hypertension
• Vasculitis (Henoch–Schonlein purpura, periarteritis nodosa, ¨
Wegener granulomatosis)

12. Other causes:
• Fever
• Strenuous exercise
• Mechanical trauma
• Menstruation
• Foreign bodies
• Instrumentation/Cathetarization
• Hypercalciuria//Hyperuricosuria
• Sickle cell disease/trait
• Coagulopathy
• Drugs/toxins :NSAIDs, anticoagulants, cyclophosphamide, ritonavir, indinavir, sulfonamide, phenytoin
• Anatomic abnormalities: (hydronephrosis, polycystic kidney disease, vascular malformations)
• Diseases of adjacent organs to urinary tract: Appendicitis, carcinoma of the rectum, carcinoma of the colon,
uterocervical cancer

14. Initial Approach
• a history and physical examination to assess risk factors for
genitourinary malignancy, medical renal disease, gynecologic and
non-malignant genitourinary causes of microhematuria.
(AUA guidelines)

15. Detailed History
• Efforts should be made to distinguish glomerular causes from
extraglomerular one:
• Passage of clots in urine suggests an extraglomerular cause
• Fever, abdominal pain, dysuria, frequency, and recent enuresis in older
children may point to a urinary tract infection as the cause
• Recent trauma to the abdomen may be indicative of hydronephrosis
• Early-morning periorbital puffiness, weight gain, oliguria, dark-colored
urine, and edema or hypertension suggest a glomerular cause,
• Hematuria due to glomerular causes is painless
• Recent throat or skin infection may suggest postinfectious
glomerulonephritis

16. • Joint pains, skin rashes, and prolonged fever in adolescents suggest a
collagen vascular disorder(Rheumatoid arthritis, Systemic lupus
erythematosus)
• Skin rashes and arthritis can occur in Henoch-Schönlein
purpura and systemic lupus erythematosus
• Information regarding exercise, menstruation, recent bladder
catheterization, intake of certain drugs or toxic substances, or passage
of a calculus may also assist in the differential diagnosis.
• A family history that is suggestive of Alport syndrome, collagen
vascular diseases, urolithiasis, or polycystic kidney disease is
important

17. Examination:
• BP and volume status is especially important when
glomerulonephritis is a consideration.
• periorbital puffiness or peripheral edema: nephrotic syndrome
• Detailed skin examination to look for purpura.
• Abdomen: palpable mass reveals a renal tumor or hydronephrosis
may exist,
• A palpable bladder after voiding indicates obstruction or retention
• Abdominal bruit: AAA
• Always check for extrarenal manifestations and co morbid conditions.
Check for other sites of bleeding

18. • PR/DRE: prostatitis, prostate cancer, BEP
• Genitalia: epididymitis, meatal stenosis, and other structural causes
of hematuria; signs of trauma
• Atrial fibrillation : renal artery embolic infarction, especially if the
patient has flank pain
• Costovertebral angle tenderness : pyelonephritis, nephrolithiasis, or
PUJ obstruction.
• Detailed ophthalmologic evaluation (in familial hematuria)

19. Diagnosis
• Urine dip strip analysis it is the most commonly used method of testing the
urine for blood is the urine test strip or dipstick, which utilizes the peroxidase-like
activity of hemoglobin to generate a color change.
• Dipstick: pH, glucose, protein, blood, bilirubin
-also useful screening test for diabetes, ketones, nitrates renal and hepatic
disease
• the simplest and most common test ,91%–100% sensitive and 65%–99% specific
for detecting more than three RBCs per hpf (Woolhandler et al., 1989).
• False-positive tests(up to 35%) may occur in the setting of myoglobinuria or
hemoglobinuria, , semen, highly alkaline urine (pH greater than 9), and
concentrated urine., confirmed by the absence of RBCs on microscopic
examination.
• False Negative: Vit C intake

20. Urinalysis
• Microscopic examination of the urinary sediment (urinalysis) is the
gold standard test.
• It not only detects the presence of RBCs, but also the morphologic
features of RBCs, the presence of white blood cells (WBCs), casts, or
crystals, hence it is helpful in distinguishing glomerular and
nonglomerular causes of hematuria.
• presence of dysmorphic RBCs (irregular outer cell membrane of
RBCs), RBC casts, or proteinuria supports a diagnosis of hematuria of
glomerular origin.

21. • Glomerular hematuria: Brown-colored urine, RBC casts, and
dysmorphic (small, deformed, misshapen, sometimes fragmented)
RBCs and proteinuria
• Nonglomerular hematuria: Reddish or pink urine, passage of blood
clots, and eumorphic/isomorphic (normal-sized, uniform, biconcavely
shaped) RBCs.

22. • If proteinuria is detected on a dipstick test, a random or 24-h
quantitative measurement can be done.
• Proteinuria >500 mg/24 h or urinary protein concentration to urine
creatinine ratio >0.3 on random specimen is typically associated with
glomerular disease.
• If clinically significant proteinuria or elevated serum creatinine is
present, the patient should be referred to a nephrologist.

23. • Phase-contrast microscopy to help determine the source of the bleeding
(urine for the presence of a significant number of dysmorphic RBCs
suggests a renal (glomerular) source of the hematuria)
• Hematologic and coagulation studies (eg,CBC, platelet counts, PT/INR)
• Blood urea nitrogen (BUN) for paraneoplastic syndrome and serum Cr
levels for kidney failure.
• RFT, PSA,
• Serologic testing (eg, complement, antistreptolysin [ASO], anti- DNase B,
antinuclear antibody [ANA], and double-stranded DNA [dsDNA])
• Urine culture for suspected UTI:midstream or clean-catch specimen

24. Imaging
• Xray KUB:Detect bony metastases, paget’s disease, soft tissue masses,
abnormal calcification
• USG abd/pelvis: Assessment of renal and scrotal masses and bladder
emptying
• CT urography (replaces IVU):Delineates entire urinary tract
• MRI
• Retrograde pyelography.
• TRUS: prostate disease
• Voiding cystourethrography
• Cystoscopy
• Renal biopsy: in nephrological cases

25. Ultrasound/USG
• Macroscopic hematuria in the absence of significant proteinuria or RBC
casts is an indication for a renal and bladder ultrasound study to exclude
malignancy or cystic renal disease.
• Urinary tract anomalies, such as hydronephrosis, hydroureter,
nephrocalcinosis, tumor, and urolithiasis, are readily revealed with
ultrasonography.
• Advantage: Compared with other imaging studies, sonography is rapid,
noninvasive, readily available, and devoid of exposure to radiation.
• Disadvantage: USG is less sensitive (50% sensitive and 95% specific) in
detecting urothelial lesions, small renal masses, and urinary calculi.
• User dependent; diagnostic uncertainty, and may lead to indeterminate
findings that result in additional imaging and costs

26. CT Urography
• it combines the benefits of conventional CT (with and without contrast) and IVU.
1. a noncontrast phase to diagnose hydronephrosis and urinary calculi,
2. a nephrogenic phase to evaluate the renal parenchyma for pyelonephritis or
neoplastic lesions, and
3. an excretory phase to detect urothelial disease, appearing as filling defects.
• CT urography is the imaging procedure of choice in the evaluation of microscopic
hematuria because of its high sensitivity (91% to 100%) and specificity (94% to
97%), and its ability to provide excellent diagnostic information in a single
imaging session.
• |Spiral CT scan is particularly useful in the detection of urolithiasis, Wilms tumor,
and polycystic kidney disease.
• Major concern: radiocontrast exposure

27. • The appropriate upper tract imaging method should be determined
by clinical circumstances, patient preferences, and available
resources.

28. Evaluation for lower tract
• Cystoscopy is recommended in all patients with asymptomatic
microscopic hematuria who present with risk factors for malignancy,
regardless of age.
• Cystoscopy can identify urethral stricture disease, benign prostatic
hyperplasia, and bladder masses.
• In patients younger than 35 years, the probability of urinary tract
malignancy is low; therefore, in the absence of risk factors,
cystoscopy should be performed at the discretion of the urologist.

29. Urine cytology
• Cytologic examination of exfoliated cells within the urine is currently a
noninvasive and cost-effective test for detecting urothelial malignancy.
• Early morning urine specimen
• Sensitivity of 40%–76%, depending on the stage of malignancy and the
expertise of the cytopathologist.
• Sensitivity is higher if the specimen tested is obtained from the first void in
the morning on three consecutive days or bladder wash during cystoscopy.
• high specificity; hence, positive urinary cytologies are almost diagnostic of
urothelial malignancy (Yun et al., 2004)
• The American Urological Association recommends that for those who
refuse cytoscopy or are considered at low risk for malignancy, voiding urine
cytologic testing alone can be done (Grossfeld et al., 2001b)

30. • Patients at high risk for uroepithelial tumors should undergo
complete evaluation with cystoscopic examination of the bladder.
• There are new, rapid urinary assays available for bladder cancer
detection (e.g., nuclear matrix protein 22 test, bladder tumor
antigen stat test, urinary bladder cancer antigen, fluorescence in
situ hybridization), but these have not been shown to be superior to
cystoscopy or cytology in the initial detection of urothelial
malignancies and should not be obtained by primary care physicians

31. Functional studies
• Function Radioisotope renography:
• Assess function of each kidney separately
-DTPA-99mTc-dimercaptosuccinic acid,
-DMSA-diethylenetriamine pentaacetic acid.
• Urodynamics: Voiding cystourethrograms are valuable in detecting urethral
and bladder abnormalities that may result in hematuria (eg, cystitis).
-Urine flow rates: Useful is assessing degree of obstruction to micturition
• Cystometry(static and ambulant): differentiate stress and urge
incontinence

32. Biopsy
Kidney biopsy is rarely indicated:
• Significant proteinuria
• Abnormal renal function
• Recurrent persistent hematuria
• Serologic abnormalities (abnormal complement, ANA, or dsDNA
levels)
• Recurrent gross hematuria
• A family history of end-stage renal disease
Hematuria workup: Dr Sanjeev Gulati et al; Medscape May10, 2020

33. Management:
• Hematuria is a sign and not itself a disease; thus, therapy should be
directed at the process causing it
• Asymptomatic (isolated) hematuria generally does not require
treatment.
• In conditions associated with abnormal clinical, laboratory, or imaging
studies, treatment may be necessary, as appropriate, with the
primary diagnosis

34. • Surgical intervention may be necessary with certain anatomic
abnormalities (eg, ureteropelvic junction obstruction, tumor, or
significant urolithiasis)
• Dietary modification is usually not indicated, except for children who
may tend to develop hypertension or edema as a result of the
primary disease process (eg, nephritis)
• Patients with persistent microscopic hematuria should be monitored
every 6-12 months for the appearance of signs or symptoms
indicative of progressive renal disease

35. Risk stratification
(AUA guidelines on hematuria 2020)

36. • In low-risk patients :repeating urinalysis within six months or
proceeding with cystoscopy and renal ultrasound.
• Low-risk patients who initially elected not to undergo cystoscopy or
upper tract imaging and who are found to have microhematuria on
repeat urine testing should be reclassified as intermediate- or high-
risk.
• In such patients, clinicians should perform cystoscopy and upper tract
imaging in accordance with recommendations for these risk strata.

37. • Intermediate risk: cystoscopy and renal ultrasound in patients with
microhematuria categorized as intermediate-risk for malignancy.
• High risk: cystoscopy and axial upper tract imaging (CT Urography or
MRI) in patients with microhematuria categorized as high-risk for
malignancy.

38. • In patients with a negative hematuria evaluation, clinicians may
obtain a repeat urinalysis within 12 months.
• For patients with a prior negative hematuria evaluation who develop
gross hematuria, significant increase in degree of microhematuria, or
new urologic symptoms, clinicians should initiate further evaluation.

39. Asymptomatic Hermaturia (AMH)
• Microscopic hematuria in the absence of an obvious benign cause
• assessment include a careful history, physical examination, and
laboratory examination to rule out benign causes of AMH such as
infection, menstruation, vigorous exercise, medical renal disease, viral
illness, trauma, or recent urological procedures.
• then the presence of asymptomatic microhematuria should prompt a
urologic evaluation: cystoscopic evaluation for age 35 and older &
who present with risk factors for urinary tract malignancies (e.g.,
irritative voiding symptoms, current or past tobacco use, chemical
exposures) regardless of age.
AUA Guidelines, 2016

40. • Initial evaluation with imaging: CT Urography, MRI
• In patients with persistent microhematuria following a negative
work up or those with other risk factors for carcinoma in situ (e.g.,
irritative voiding symptoms, current or past tobacco use, chemical
exposures), cytology may be useful.
• For persistent asymptomatic microhematuria after negative urologic
work up, yearly urinalyses should be conducted.

43. Dutch Guideline 2018

48. Follow-up
• If appropriate workup does not reveal nephrologic or urologic
disease, then annual urinalysis should be performed for at least two
years after initial referral.
• If these two urinalyses do not show persistent hematuria, the risk of
future malignancy is less than 1%, and the patient may be released
from care.
• However, if asymptomatic microscopic hematuria persists on follow-
up urinalysis, a full repeat evaluation should be considered within
three to five years of the initial evaluation.
• Patients' risk factors for urologic malignancy should guide clinical
decision making about reevaluation

49. Take home message
• Every case of hematuria requires investigation. Macrohematuria requires more
extensive investigation.
• Because of the lack of high-quality scientific evidence, there are no consistent
guideline recommendations for the investigation of hematuria, especially
asymptomatic microhematuria.
• Findings of red cell casts, large numbers of dysmorphic red blood cells, or more
than 5% acanthocytes indicate the presence of glomerular hematuria, which
requires a nephrology referral.
• For a basic investigation, for all patients a history should be taken and clinical and
laboratory tests carried out, and possibly also red cell morphology studies and
renal and bladder ultrasonography.
• Patients who have been exposed to exogenous toxins (including tobacco smoke),
are older, are of male sex, or have macrohematuria, should be further
investigated by urethrocystoscopy and perhaps CT urography.

50. References
• Sharp VJ, Barnes KT, Erickson BA. Assessment of asymptomatic
microscopic hematuria in adults. Am Fam Physician. 2013;88(11):747-
754
• Shen X. Diagnostic algorithm for the evaluation of hematuria. J Am
Acad Nurse Pract. 2010;22(4):186-191.
• Bolenz C, Schröppel B et al. The Investigation of Hematuria. Dtsch
Arztebl Int. 2018 Nov 30;115(48):801-807.
• American Urological Association Guidelines : Microhematuria:
AUA/SUFU Guideline 2020