3. Definition
• Macroscopic (gross) Hematuria
Visible (Red Urine)
• Microscopic Hematuria
>3RBC/HPF from two of three urinary sediments without a
urinary tract infection, or menstruation on microscopic
evaluation
4. Definition of positivity
• Urine dipstick of a fresh voided urine sample, containing no
preservative, is considered a sensitive means of detecting the
presence of hematuria.
• Routine microscopy for confirmation of dipstick haematuria
12. Exercise induced hematuria
•Gross or microscopic hematuria that occurs after strenuous exercise and resolves
with rest
•Direct trauma to the kidneys and/or bladder may be responsible for the hematuria
•Renal ischemia due to shunting of blood to exercising muscles
•Exercise-induced gross hematuria should be differentiated from two other potential
causes of red to brown urine following exercise: myoglobinuria due to
rhabdomyolysis; and march hemoglobinuria
•Evaluation is not warranted in patients under age fifty who are not at increased risk
for bladder or kidney cancer
•Evaluation for other causes of hematuria is warranted if the hematuria persists well
beyond one week
14. Causes
• Any Glomerular disease may present with Hematuria
• Approximately 50 percent of patients with idiopathic
hematuria have a glomerular disease
• Most patients also have other signs such as proteinuria, red
cell casts, or renal insufficiency
• There are three disorders that account for most cases of
persistent isolated hematuria due to glomerular disease: IgA
nephropathy, Hereditary nephritis (Alport syndrome), and thin
basement membrane nephropathy
15. Thin basement membrane disease or benign familial
hematuria
• Mutations of the type IV collagen genes COL4A3 and COL4A4
• TBMN is often familial, probably with autosomal dominant inheritance
• A family history of hematuria is noted in 30 to 50 percent of cases
• Persistent or intermittent asymptomatic microscopic hematuria
• The long-term prognosis is excellent in most patients with true thin
basement membrane nephropathy
• We don't biopsy these patients
• Slowly progressive renal insufficiency can occur and is often manifested on
renal biopsy by focal segmental glomerulosclerosis
16. Uniform thinning of lamina dense of glomerular basement membrane to 200
nm in > 50% of glomerular capillaries
17. Alport syndrome
• Inherited progressive form of glomerular disease
• Often associated with sensorineural hearing loss and ocular
abnormalities
• Primary basement membrane disorder arising from mutations in
genes encoding several members of the type IV collagen protein
family
• X-linked (80%)• Autosomal recessive (15%)• Autosomal dominant
(5%)
• Initial renal manifestation of Alport syndrome is asymptomatic
persistent microscopic hematuria, which is present in early
childhood in affected patients
• ESRD usually occurs between the ages of 16 and 35 years in
patients with X-linked or autosomal recessive disease and they end
up on dialysis
19. The following 10 criteria of which 4 must be met for the diagnosis of Alport
syndrome
• Family history of nephritis of unexplained haematuria in a first degree relative of the index case or in a male relative
linked through any numbers of females.
• Persistent haematuria without evidence of another possibly inherited nephropathy such as thin GBM disease, polycystic
kidney disease or IgA nephropathy.
• Bilateral sensorineural hearing loss in the 2000 to 8000 Hz range.
• The hearing loss develops gradually, is not present in early infancy and commonly presents before the age of 30 years.
• A mutation in COL4A.
• Immunohistochemical evidence of complete or partial lack of the Alport epitope in glomerular, or epidermal basement
membranes, or both.
• Widespread GBM ultrastructural abnormalities, in particular thickening, thinning and splitting.
• Ocular lesions including anterior lenticonus, kerataconus, posterior subcapsular cataract, posterior polymorphous
dystrophy and retinal flecks.
• Macrothrombocytopenia or granulocytic inclusions.
• Diffuse leiomyomatosis of esophagus or female genitalia, or both.
20. Light microscopy shows mesangial cell proliferation and capillary wall
thickening, progressing to glomerular sclerosis and tubulo-interstitial changes
21. This shows glomerular basement membrane changes including
splitting of lamina densa and lamellation
25. IgA nephropathy
• IgA nephropathy is the most common cause primary glomerulonephritis
• 2:1 male to female predominance
• Greatest frequency in Asians and Caucasians
• Relatively rare in blacks
• Negative family history
• See in someone with a recent history of cold or sore throat and then
they have hematuria
26. IgA nephropathy: pathogenesis
• The initiating event in the pathogenesis of IgA nephropathy is
the mesangial deposition of IgA
• There is reduced galactosylation and variable changes in
sialylation of the IgA1 hinge region O-glycans
27. Diagnosis of IgA
• kidney biopsy = IgA deposition on mesangium-pathognomnic
finding = seen on immunofluroescence = prominent, globular
deposits of IgA in mesangium and to lesser degree along
glomerular capillary wall
31. C/P of IgA
• One or recurrent episodes of gross hematuria, usually
following an upper respiratory infection
• Microscopic hematuria and usually mild proteinuria
• Nephrotic syndrome
•
• Acute rapidly progressive glomerulonephritis
32. Prognosis of IgA
• if you see high proteinuria then it is a bad prognosis. If you
see little proteinuria then there is a good prognosis.
• Patients with IgA nephropathy and little or no proteinuria
(<500 mg/day) have a low risk of progression in the short
term.
• Among patients who develop overt proteinuria and/or
elevated serum creatinine concentration, progression to ESRD
is approximately 15 to 25 percent at 10 years and 20 to 30
percent at 20 years.
33. Treatment of IgA
1. NONIMMUNOSUPPRESSIVE THERAPIES
• The optimal approach to the treatment of IgA nephropathy is
uncertain
• Angiotensin converting enzyme (ACE) inhibitors or angiotensin
II receptor blockers (ARB) both for blood pressure control and
to slow progression of the renal disease, cut down on the
proteinuria
• Fish oil, safe to use and does not cause problems
2. IMMUNOSUPPRESSIVE THERAPY
• Glucocorticoids
• Cytotoxic agents
34. Secondary IgA nephropathy
• A variety of systemic diseases are associated with IgA
nephropathy such as liver failure, celiac disease, rheumatoid
arthritis, Reiter's disease, ankylosing spondylitis and HIV.
35. Henoch–Schönlein purpura
• HSP is a systemic vasculitis (inflammation of blood vessels)
and is characterized by deposition of immune complexes
containing the antibody IgA.
• Rash, arthritis, abdominal pain and hematuria
37. C/P of poststrept GN
• In general, the latent period is 1-2 weeks after a throat infection and 3-6 weeks
after a skin infection.
• Dark urine (brown-, tea-, or cola-colored)This is often the first clinical symptom.
• Dark urine is caused by hemolysis of red blood cells that have penetrated the
glomerular basement membrane and have passed into the tubular system.
• The onset of puffiness of the face or eyelids is sudden. It is usually prominent
upon awakening and, if the patient is active, tends to subside at the end of the
day
• In some cases, generalized edema and other features of circulatory congestion,
such as dyspnea, may be present.
• Edema is a result of a defect in renal excretion of salt and water.
38. Laboratory investigations
• Evidence of preceding streptococcal infection
1. Antibody titers to extracellular products of streptococci are positive in
more than 95% of patients with pharyngitis and 80% of patients with
skin infections.
2. The antistreptolysin (ASO), antinicotinamide adenine dinucleotidase
(anti-NAD), antihyaluronidase (AHase), and anti–DNAse B are commonly
positive after pharyngitis, and anti–DNAse B and AHase titers are more
often positive following skin infections.
• Serologic findings: Low serum complement levels indicative of an
antigen-antibody interaction are a universal finding in the acute phase of
APSGN.
40. Hypercellularity of the glomeruli
The cell types typically present include endothelial and mesangial cells and
migrant inflammatory cells, which include polymorphonuclear leukocytes and
monocytes
41. Deposits of immunoglobulin G and C3 in a diffuse granular pattern are present along
the glomerular capillary wall and mesangium
42. The most consistent and classic diagnostic finding is the presence of
glomerular subepithelial electron-dense immune-type deposits
43. DD of acute Nephritis
• Lupus nephritis
• Cryoglobulinemia
• Anti GBM disease
• Membranoprolilerative GN
45. Localization of Hematuria
• Glomerular
– Brown or tea-
colored
– RBC cast, cellular
cast
Tubular cells
– Proteinuria >2+
– Dysmorphic
erythrocytes
• Non-glomerular
– Red-pink urine
– Blood clots
– No proteinuria or
<2
– Normal
morphology of
erythrocytes
46. Hematuria
• Patient comes to your office complaining that
their urine is reddish in color...
•What is your first step?
47. 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.
51. HEMOGLOBINURIA
RBC abnormality
• Defects of RBC membrane structure and function
(hereditary spherocytosis)
• Deficiency of enzymes (favism)
• Hemoglobinopathy (thalassemia)
• PNH
52. Phase-contrast microscopy
to distinguish glomerular from post glomerular
bleeding
• post glomerular bleeding: normal size and shape
of RBC
• glomerular bleeding: dysmorphic RBC
(acanthocyte)
55. 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.
• It has been shown in multiple studies that the addition of
urine cytology in the primary analysis of hematuria does not
contribute to diagnosis which is usually made by cystoscopy
or imaging.
56. Urine Culture
• The addition of cultures of urine may be
indicated if the sediment shows leukocytes.
58. Immunology
• Antinuclear antibody (ANA) , Anti-double stranded (ds)
antibody
• C3 & C4 complement concentrations
– Low in SLE, acute post infectious
glomerulonephritis, Cryoglobulinemia
• ASO titre
– High after streptococcal infection
59. Serology
• Hepatitis B and C, HIV serology
• ANCA test for diagnosis of vascuilitis
• Anti-GBM antibodies in GP syndrome
C-ANCA P-ANCA
60. Cystoscopy
• The American Urological Association best practice policy
suggests that, in patients at low risk for urothelial cancer,
cystoscopy may be avoided.
• Imaging of the bladder should preferably precede cystoscopy,
so it can aid the urologist and improve diagnostic yield.
61. Radiologic Diagnosis of Hematuria
• Radiologic imaging plays a pivotal role in the
diagnosis of hematuria
• No specific diagnostic algorithm for hematuria
62. Abdominal Radiographs
• Its overall sensitivity for renal and ureteral stones is
only 45–60% in multiple studies
63. 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
65. 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 (19–32%) for stone
detection,
67. Excretory Urography
• For hematuria, multiple studies have now shown the
superiority of CT urography over excretory
urography.
• There is also a low sensitivity (< 60%) for renal
tumors smaller than 3 cm for excretory urography
68.
69. 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
70. 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.
71. Nephrological referral + biopsy
• Evidence of declining GFR (by >10ml/min at any stage within the previous
5 years or by >5ml/min within the last 1 year)
• Stage 4 or 5 CKD (eGFR <30ml/min)
• Significant proteinuria
• Isolated hematuria with hypertension in those aged <40
• Visible haematuria coinciding with intercurrent (usually upper respiratory
tract) infection
73. 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?
74. 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 ANEMIA
75. Quiz time #2
• Gross hematuriain 6 year old boy 3 days
following a URI
• What is your diagnosis?
76. IgA Nephropathy (Berger’s Disease)
• IgA deposits seen on renal biopsy
• nl C3
• elevated IgA in 15%
• often hypertensive
• need long-term f/u
77. 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?
78. 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 High BP, proteinuria, hematuria for up to 3
mos after initial presentation
79. Quiz time #4
• 14 years female with hematuria
• More “tired” lately
