Hematuria

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Hematuria

• For Surgical Board...
• Dr. M. El-Shazly
• MD Urology

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• Hematuria is a frequent reason for physician
  consultation in clinical practice up to 8-20 of
  urology consultations (Messing et al., 2006).

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Definition

• Macroscopic (gross) Hematuria (VH)
• visible to the human eye
• (Red Urine)
• Microscopic Hematuria (NVH)
• gt3RBC/hpf from two of three urinary sediments
  without a urinary tract infection, or
  menstruation on microscopic evaluation
• (Grossfeld et al., 2001)

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• Hematuria can be caused by a variety of
  urothelial, vascular, glomerular, interstitial
  disorders.

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• The main focus in the workup of hematuria is
  tumor detection, either urothelial cell cancer or
  renal cell carcinoma (RCC).

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Definition of positivity

• Urine dipstick of a fresh voided urine sample,
  containing no preservative, is considered a
  sensitive means of detecting the presence of
  haematuria.
• Routine microscopy for confirmation of dipstick
  haematuria is not necessary.

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• Significant haematuria is considered to be 1 or
  greater. Trace haematuria should be considered
  negative

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• Trace versus 1
• Significant haematuria is considered to be 1 or
  greater.
• Trace haematuria should be considered negative

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What is significant haematuria?

• a) Any single episode of VH.
• b) Any single episode of s-NVH (in absence of UTI
  or other transient causes).
• c) Persistent a-NVH (in absence of UTI or other
  transient causes). Persistence is defined as 2
  out of 3 dipsticks positive for NVH.

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Transient causes to be excluded

• Urinary tract infection (UTI)
• - A negative dipstick result for both leucocytes
  and nitrites. Otherwise an MSU negative for
  pyuria and culture are required.
• Exercise induced haematuria or rarely
  myoglobinuria
• Menstruation.

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Urological referral

• The following patients require direct referral to
  urology for further investigation.
• All patients with visible haematuria (any age).
  
• All patients with s-NVH (any age).
• All patients with a-NVH aged 40 yrs.

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Glomerular Hematuria

• brown, tea colored urine
• proteinuria
• deformed urinary RBCs
• RBC casts

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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

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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

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Extraglomerular Hematuria

• Hematuria from lower urinary tract
• terminal hematuria
• blood clots
• nl urinary RBCs
• minimal proteinuria

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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

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Nephrological referral

• Evidence of declining GFR (by gt10ml/min at any
  stage within the previous 5 years or by gt5ml/min
  within the last 1 year)
• Stage 4 or 5 CKD (eGFR lt30ml/min)
• Significant proteinuria
• Isolated haematuria with hypertension in those
  aged lt40.
• Visible haematuria coinciding with intercurrent
  (usually upper respiratory tract) infection

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Nephrologic Causes of Hematuria

• Nephrologic causes of hematuria should be
  considered early in the workup of both
  microscopic and macroscopic hematuria because up
  to 10 of cases of hematuria can be nephrologic
  (Khadra et al., 2000).
• The most frequent causes include IgA nephropathy
  and thin basement membrane nephropathy.

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Nephrologic Causes of Hematuria

• There is no simple test to differentiate urologic
  from nephrologic hematuria. Most tests depend on
  pattern recognition and urinalysis, especially
  the urine sediment. The most important clues
  include the presence of hypertension, reduced
  renal function, proteinuria, and the presence of
  dysmorphic erythrocytes in the urine sediment.

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Nephrologic Causes of Hematuria

• If the percentage of dysmorphic erythrocytes
  increases above 20, a glomerular cause is
  likely if the percentage of dysmorphic
  erythrocytes is above 80, a glomerular cause is
  almost certain

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The Clinical Picture Microscopic Versus
Macroscopic Hematuria

• The traditional risk factors for malignancy
  include macroscopic hematuria, smoking, age, sex,
  micturition complaints, urothelial cancer,
  radiotherapy of the pelvis, and working with
  aromatic amines in the chemical industry

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Macroscopic Hematuria

• The risk for malignancy is high. Malignancy can
  be found in 1028 of cases overall and in up to
  10 of patients younger than 40 years Booman et
  al., 2001)).
• In the study of Edwards et al. 13, upper
  urinary tract urothelial cell cancer was found in
  0.5 and RCC in 2 of patients, and 16.5 of
  patients were diagnosed with bladder cancer
  (90).(Edwards et al., 2006)

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• Recurrent Microscopic Hematuria
• The risk of urologic malignancy is much lower
  with microscopic than with macroscopic hematuria.
  Depending on the population studied, in up to
  8.9 of patients with recurrent microscopic
  hematuria, a malignancy was found
  Interestingly, In the largest cohort studied,
  upper urinary tract urothelial cell cancer was
  found in 0.2, RCC in 1, and bladder cancer

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Localization of Hematuria

• Glomerular
• Brown or tea-colored
• RBC cast, cellular cast
• Tubular cells
• Proteinuria gt2
• Dysmorphic erythrocytes
• Erythrocyte volume lt50 um3

• Non-glomerular
• Red-pink urine
• Blood clots
• No proteinuria or lt2
• Normal morphology of erythrocytes
• Erythrocyte volume gt 50 um3

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Hematuria

• Patient comes to your office complaining that
  their urine is reddish in color...
• What is your first step?

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Laboratory Diagnosis of Hematuria

• Urinalysis
• Even though most urine samples are early morning
  urine, for analysis of corpuscular elements, the
  so-called second morning urine is more suitable
  and recommended.
• Analysis should follow rapidly, preferably within
  1 hour for sediment analysis and 2 hours for
  dipstick testing.

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Urine Cytology

• The sensitivity of urine cytology for the
  diagnosis of urothelial cell cancer is low, and a
  negative result does not exclude patients from
  further testing (Rodgers et al., 2006.
• It has been shown in multiple studies that the
  addition of urine cytology in the primary
  analysis of hematuria does not contribute to
  diagnosis Hovius et al., 2008, which is usually
  made by cystoscopy or imaging.

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Urine Culture

• The addition of cultures of urine may be
  indicated if the sediment shows leukocytes.

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Clinical Chemistry

• Important to support a nephrologic diagnosis
• RFT
• Coagulation profile

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Cystoscopy

• Flexible cystoscopy remains the reference
  standard for diagnosis of hematuria of the lower
  urinary tract

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Cystoscopy

• The American Urological Association best practice
  policy suggests that, in patients at low risk for
  urothelial cancer, cystoscopy may be avoided 4,
  5. Imaging of the bladder should preferably
  precede cystoscopy, so it can aid the urologist
  and improve diagnostic yield.

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Ureterorenoscopy

• Upper tract gross hematuria
• (Unilateral hematuria)
• Urothelial tumors ofupper urinary tract if
  imaging is not conclusive and negative cytology

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Radiologic Diagnosis of Hematuria

• Radiologic imaging plays a pivotal role in the
  diagnosis of hematuria
• No specific diagnostic algorithm for hematuria

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Abdominal Radiographs

• Its overall sensitivity for renal and ureteral
  stones is only 4560 in multiple studies (Ege et
  al., 2004)

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Non-contrast CT

• It is now the reference standard for stone
  detection, and even very-low-dose unenhanced CT
  techniques with a radiation dose comparable to
  that of abdominal radiographs have shown better
  results (Kluner et al., 2006)

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Ultrasound

• Ultrasound is suitable as first-line diagnostic
  test
• In comparison with excretory urography,
  ultrasound showed a higher sensitivity for
  bladder tumors and equal (i.e., moderate)
  sensitivity for upper urinary tract tumors.
  Ultrasound alone is not sensitive (1932) for
  stone detection,

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Excretory Urography

• For hematuria, multiple studies have now shown
  the superiority of CT urography over excretory
  urography. There is also a low sensitivity (lt
  60) for renal tumors smaller than 3 cm for
  excretory urography

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Retrograde Ureteropyelography

• However, with the increasing use of MDCT
  urography and ureterorenoscopy, its role has
  diminished significantly. It has been shown that,
  in high-risk patients, CT urography is equivalent
  to retrograde ureteropyelography in the upper
  urinary tract

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CT Urography

• For identification of the cause of hematuria, the
  overall sensitivity is 92100, and the
  specificity is 8997 (Albani et al.,2007
  Sudakoff et al., 2008)

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Radiation Exposure

• KUB 0.20.7 mSv
• CTKUB (23 mSv)
• CTU (9-16 mSv)

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• Imaging is key in the analysis of hematuria, but
  it should be realized that CT urography is a
  high-dose examination, upper urinary tract
  urothelial cell cancer is a rare disease, and the
  risk for malignancy in many patients with
  microscopic hematuria is relatively low.
  Therefore, the use of CT urography should be
  justified by weighing benefits versus risks, and
  CT urography protocols should be optimized to
  radiation dose.

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• Therefore, the use of CT urography should be
  justified by weighing benefits versus risks, and
  CT urography protocols should be optimized to
  radiation dose.

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• This can be accomplished well by this risk-based
  approach to the work-up of hematuria, whereby
  initial screening is performed with ultrasound
  and CT urography as a first-line modality is
  reserved for patients at high risk of malignancy.

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MR Urography (MRU)

• MRU has inherent advantages in that it does not
  require ionizing radiation, has a high contrast
  resolution, has good sensitivity for contrast
  media, and has the possibility for better tissue
  characterization than other imaging techniques do

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MR Urography (MRU)

• However, MRU is costly, technically demanding,
  and not widely practiced. Therefore, MRU
  expertise is available only in specific dedicated
  centers.
• It is good for pediatric diseases and for the
  evaluation of obstructive disease (Silverman et
  al., 2009)

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A Vision for the Future

• Validated Scoring System

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Quiz Time

• Lets see who has been paying attention...

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Quiz time 1

• 10 yr old boy coming in for school physical.
  Found to have 30 RBC/hpf on microscopic analysis.
  
• Family Hx reveals uncle used to have blood in
  his urine
• What is your diagnosis?

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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

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Quiz time 2

• Gross hematuriain 6 year old boy 3 days following
  a URI
• What is your diagnosis?

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IgA Nephropathy (Bergers Disease)

• IgA deposits seen on renal biopsy
• nl C3
• elevated IgA in 15
• often hypertensive
• need long-term f/u

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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?
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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

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Quiz time 4

• 14yo female with hematuria
• More tired lately

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Quiz time 5
last one!

• Referral from nephrology, patient with
  steroid-resistent nephrotic syndrome started
  cyclophosphamide treatment 2 days ago and
  developed severe gross hematuria???

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Quiz time 5

• She was in a car crash 3 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?

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• Thank you for your attention!