1. GLOMERULONEPHRITIDES
SIMON E. PRINCE, D.O., F.A.C.P., F.A.S.N.
Clinical Assistant Professor of Medicine
NYU School of Medicine
Sunday, March 15, 2009

2. Classic Patterns of
Glomerular Diseases
Sunday, March 15, 2009

3. Classic Patterns of
Glomerular Diseases
Distinguished by clinical factors
and urinary sediment
NEPHROTIC
NEPHRITIC
Sunday, March 15, 2009

4. NEPHROTIC
Sunday, March 15, 2009

5. NEPHROTIC
Nephrosis:
Urinary sediment: “Bland”
Heavy proteinuria and lipiduria
Few cells or casts
Less often HTN
Relatively preserved renal function
Sunday, March 15, 2009

6. Sunday, March 15, 2009

7. NEPHRITIC SYNDROME
Sunday, March 15, 2009

8. NEPHRITIC SYNDROME
Focal vs Diffuse Nephritic (Glomerulonephritis)
Rapidly progressive GN
Acute GN
Chronic GN
Sunday, March 15, 2009

9. NEPHRITIC SYNDROME
Focal vs Diffuse Nephritic (Glomerulonephritis)
Rapidly progressive GN
Acute GN
Chronic GN
Usually caused by Immunocomplex (Ag-Ab)
reaction and deposition in the GBM
Sunday, March 15, 2009

10. NEPHRITIC SYNDROME
Focal vs Diffuse Nephritic (Glomerulonephritis)
Rapidly progressive GN
Acute GN
Chronic GN
Usually caused by Immunocomplex (Ag-Ab)
reaction and deposition in the GBM
Some disorders Immunocomplex formation happens
distal to the GBM and deposit in the
subepithelial space
Sunday, March 15, 2009

11. Clinical Characteristics
of NEPHRITIC SYNDROME
Sunday, March 15, 2009

12. Clinical Characteristics
of NEPHRITIC SYNDROME
Urinary sediment:
“Active”
RBCs (dysmorphic),
RBC Casts, Granular
casts
Sunday, March 15, 2009

13. Clinical Characteristics
of NEPHRITIC SYNDROME
Urinary sediment:
“Active”
RBCs (dysmorphic),
RBC Casts, Granular
casts
Varying degrees of
proteinuria (often not
nephrotic range)
Sunday, March 15, 2009

14. Clinical Characteristics
of NEPHRITIC SYNDROME
Urinary sediment:
“Active”
RBCs (dysmorphic),
RBC Casts, Granular
casts
Varying degrees of
proteinuria (often not
nephrotic range)
Hypertension
Sunday, March 15, 2009

15. Nephritic
Characteristics
Decreased renal function:
Sudden onset of ARF can be
seen
Days-weeks: Rapidly
progressive GN (RPGN)
Oliguria: <400 ml urine
output/day
Extracellular fluid
expansion- Edema
Sunday, March 15, 2009

16. Nephritic syndrome
Sunday, March 15, 2009

17. Focal
Glomerulonephritis
Sunday, March 15, 2009

18. Focal
Glomerulonephritis
Associated with inflammatory lesions in less
than ½ glomeruli on LM
Sunday, March 15, 2009

19. Focal
Glomerulonephritis
Associated with inflammatory lesions in less
than ½ glomeruli on LM
Usually mild proteinuria (<1.5 g/d)
Sunday, March 15, 2009

20. Focal
Glomerulonephritis
Associated with inflammatory lesions in less
than ½ glomeruli on LM
Usually mild proteinuria (<1.5 g/d)
Dysmorphic RBCs and occasional RBC cast
Sunday, March 15, 2009

21. Focal
Glomerulonephritis
Associated with inflammatory lesions in less
than ½ glomeruli on LM
Usually mild proteinuria (<1.5 g/d)
Dysmorphic RBCs and occasional RBC cast
Can present with asymptomatic hematuria and
proteinuria
Sunday, March 15, 2009

22. Focal
Glomerulonephritis
Associated with inflammatory lesions in less
than ½ glomeruli on LM
Usually mild proteinuria (<1.5 g/d)
Dysmorphic RBCs and occasional RBC cast
Can present with asymptomatic hematuria and
proteinuria
Gross hematuria can be seen (IgA Nephropathy)
Sunday, March 15, 2009

23. Focal
Glomerulosclerosis
Sunday, March 15, 2009

24. Focal
Glomerulosclerosis
Less than 15 yrs old
Post Infectious GN, IgA Nephropathy, Thin
Basement Membrane Disease, Hereditary
Nephritis, HSP, MPGN
Sunday, March 15, 2009

25. Focal
Glomerulosclerosis
Less than 15 yrs old
Post Infectious GN, IgA Nephropathy, Thin
Basement Membrane Disease, Hereditary
Nephritis, HSP, MPGN
15-40 yrs old
IgA Nephropathy, Thin Basement Membrane
Disease, SLE, Hereditary Nephritis, MPGN
Sunday, March 15, 2009

26. Focal
Glomerulosclerosis
Less than 15 yrs old
Post Infectious GN, IgA Nephropathy, Thin
Basement Membrane Disease, Hereditary
Nephritis, HSP, MPGN
15-40 yrs old
IgA Nephropathy, Thin Basement Membrane
Disease, SLE, Hereditary Nephritis, MPGN
>40 yr old
IgA Nephropathy, MPGN
Sunday, March 15, 2009

27. Diffuse
Glomerulonephritis
Sunday, March 15, 2009

28. Diffuse
Glomerulonephritis
Affects most or all glomeruli
Sunday, March 15, 2009

29. Diffuse
Glomerulonephritis
Affects most or all glomeruli
More active urine
Sunday, March 15, 2009

30. Diffuse
Glomerulonephritis
Affects most or all glomeruli
More active urine
Greater degree of proteinuria up to nephrotic
range can be seen
Sunday, March 15, 2009

31. Diffuse
Glomerulonephritis
Affects most or all glomeruli
More active urine
Greater degree of proteinuria up to nephrotic
range can be seen
HTN more common
Sunday, March 15, 2009

32. Diffuse
Glomerulonephritis
Affects most or all glomeruli
More active urine
Greater degree of proteinuria up to nephrotic
range can be seen
HTN more common
Renal insufficiency
Sunday, March 15, 2009

33. Diffuse
Glomerulonephritis
Affects most or all glomeruli
More active urine
Greater degree of proteinuria up to nephrotic
range can be seen
HTN more common
Renal insufficiency
Edema
Sunday, March 15, 2009

34. Diffuse
Glomerulonephritis
Sunday, March 15, 2009

35. Diffuse
Glomerulonephritis
Less than 15 yr old
Postinfectious GN, MPGN
Sunday, March 15, 2009

36. Diffuse
Glomerulonephritis
Less than 15 yr old
Postinfectious GN, MPGN
15-40 yr old
Postinfectious GN, SLE, RPGN, MPGN
Sunday, March 15, 2009

37. Diffuse
Glomerulonephritis
Less than 15 yr old
Postinfectious GN, MPGN
15-40 yr old
Postinfectious GN, SLE, RPGN, MPGN
40+ yr old
RPGN, Vasculitis, Postinfectious
Sunday, March 15, 2009

38. Hypocomplementemia
Sunday, March 15, 2009

39. Hypocomplementemia
Lab findings: Low levels of C3, C4, CH50
Sunday, March 15, 2009

40. Hypocomplementemia
Lab findings: Low levels of C3, C4, CH50
Due to complement activation by immune deposits
at a rate greater than that at which new
complement proteins can be synthesized
Sunday, March 15, 2009

41. Hypocomplementemia
Lab findings: Low levels of C3, C4, CH50
Due to complement activation by immune deposits
at a rate greater than that at which new
complement proteins can be synthesized
In addition to increased consumption, two other
mechanisms can account for hypocomplementemia in
glomerular disease:
hereditary complement deficiency
presence of circulating factors that promote
complement activation
Sunday, March 15, 2009

42. DDx of Glomerular Disease
with Hypocomplementemia
Sunday, March 15, 2009

43. DDx of Glomerular Disease
with Hypocomplementemia
Membranoproliferative GN
Sunday, March 15, 2009

44. DDx of Glomerular Disease
with Hypocomplementemia
Membranoproliferative GN
PSGN
Sunday, March 15, 2009

45. DDx of Glomerular Disease
with Hypocomplementemia
Membranoproliferative GN
PSGN
SLE
Sunday, March 15, 2009

46. DDx of Glomerular Disease
with Hypocomplementemia
Membranoproliferative GN
PSGN
SLE
Cryoglobulinemia
Sunday, March 15, 2009

47. DDx of Glomerular Disease
with Hypocomplementemia
Membranoproliferative GN
PSGN
SLE
Cryoglobulinemia
Also seen:
Endocarditis
Atheroembolic disease
Sunday, March 15, 2009

48. Hereditary Nephritis
Sunday, March 15, 2009

49. Hereditary Nephritis
Sunday, March 15, 2009

50. Alport’s
Syndrome
Sunday, March 15, 2009

51. Alport’s
Syndrome
Classically X-linked (80-85%)
Sunday, March 15, 2009

52. Alport’s
Syndrome
Classically X-linked (80-85%)
Mutation on the COL4A5 gene responsible for
the alpha 5 chain of type IV collagen in the
GBM
Sunday, March 15, 2009

53. Alport’s
Syndrome
Classically X-linked (80-85%)
Mutation on the COL4A5 gene responsible for
the alpha 5 chain of type IV collagen in the
GBM
Sensorineural hearing loss
Sunday, March 15, 2009

54. Alport’s
Syndrome
Classically X-linked (80-85%)
Mutation on the COL4A5 gene responsible for
the alpha 5 chain of type IV collagen in the
GBM
Sensorineural hearing loss
Ocular defects
Anterior lenticonus, posterior polymorphous
corneal dystrophy and retinal flecks
Sunday, March 15, 2009

55. Alport’s Syndrome
Pathology
Sunday, March 15, 2009

56. Alport’s Syndrome
Pathology
Thickened, fraying, laminated GBM
seen with EM
Sunday, March 15, 2009

57. Alport’s Syndrome
Clinical Course
Sunday, March 15, 2009

58. Alport’s Syndrome
Clinical Course
Microscopic hematuria occurs from birth
Sunday, March 15, 2009

59. Alport’s Syndrome
Clinical Course
Microscopic hematuria occurs from birth
Gross hematuria after exercise or fever
Sunday, March 15, 2009

60. Alport’s Syndrome
Clinical Course
Microscopic hematuria occurs from birth
Gross hematuria after exercise or fever
Urinary RBCs dysmorphic with RBC casts
Sunday, March 15, 2009

61. Alport’s Syndrome
Clinical Course
Microscopic hematuria occurs from birth
Gross hematuria after exercise or fever
Urinary RBCs dysmorphic with RBC casts
Proteinuria varies; occasional nephrotic range
Sunday, March 15, 2009

62. Alport’s Syndrome
Clinical Course
Microscopic hematuria occurs from birth
Gross hematuria after exercise or fever
Urinary RBCs dysmorphic with RBC casts
Proteinuria varies; occasional nephrotic range
Hemizygous males inevitably progress to ESRD;
females generally less severe
Sunday, March 15, 2009

63. Alport’s Syndrome
Clinical Course
Microscopic hematuria occurs from birth
Gross hematuria after exercise or fever
Urinary RBCs dysmorphic with RBC casts
Proteinuria varies; occasional nephrotic range
Hemizygous males inevitably progress to ESRD;
females generally less severe
No specific therapy
Sunday, March 15, 2009

64. Thin Basement
Membrane Disease
Sunday, March 15, 2009

65. Thin Basement
Membrane Disease
AKA: Benign Familial Hematuria
Sunday, March 15, 2009

66. Thin Basement
Membrane Disease
AKA: Benign Familial Hematuria
Relatively common with EM findings of thin GBM
(<225nm… normal 300-400nm)
Sunday, March 15, 2009

67. Thin Basement
Membrane Disease
AKA: Benign Familial Hematuria
Relatively common with EM findings of thin GBM
(<225nm… normal 300-400nm)
Usually AD inheritance
Sunday, March 15, 2009

68. Thin Basement
Membrane Disease
AKA: Benign Familial Hematuria
Relatively common with EM findings of thin GBM
(<225nm… normal 300-400nm)
Usually AD inheritance
Asymptomatic microscopic hematuria most often
presentation
Sunday, March 15, 2009

69. Thin Basement
Membrane Disease
AKA: Benign Familial Hematuria
Relatively common with EM findings of thin GBM
(<225nm… normal 300-400nm)
Usually AD inheritance
Asymptomatic microscopic hematuria most often
presentation
Rare episodes of gross hematuria possible
Sunday, March 15, 2009

70. Thin Basement
Membrane Disease
AKA: Benign Familial Hematuria
Relatively common with EM findings of thin GBM
(<225nm… normal 300-400nm)
Usually AD inheritance
Asymptomatic microscopic hematuria most often
presentation
Rare episodes of gross hematuria possible
Rarely associated with FSGS and progressive
renal decline
Sunday, March 15, 2009

71. Thin Basement
Membrane Disease
Sunday, March 15, 2009

72. IgA Nephropathy
Sunday, March 15, 2009

73. IgA Nephropathy
Sunday, March 15, 2009

74. IgA Nephropathy
Most common cause of primary glomerular
disease in the world
Sunday, March 15, 2009

75. IgA Nephropathy
Most common cause of primary glomerular
disease in the world
First described in 1968 by Berger in France
(AKA Berger’s Disease)
Sunday, March 15, 2009

76. IgA Nephropathy
Most common cause of primary glomerular
disease in the world
First described in 1968 by Berger in France
(AKA Berger’s Disease)
Affects all ages
most commonly children/young adults
Sunday, March 15, 2009

77. IgA Nephropathy
Most common cause of primary glomerular
disease in the world
First described in 1968 by Berger in France
(AKA Berger’s Disease)
Affects all ages
most commonly children/young adults
Male > Female 2:1
Sunday, March 15, 2009

78. IgA Nephropathy
Most common cause of primary glomerular
disease in the world
First described in 1968 by Berger in France
(AKA Berger’s Disease)
Affects all ages
most commonly children/young adults
Male > Female 2:1
Most common in Asians and Caucasians
Sunday, March 15, 2009

79. Presentation of
IgA Nephropathy
Sunday, March 15, 2009

80. Presentation of
IgA Nephropathy
40-50% cases have URI with episode of gross
hematuria as presenting Sx (synpharyngitic)
Sunday, March 15, 2009

81. Presentation of
IgA Nephropathy
40-50% cases have URI with episode of gross
hematuria as presenting Sx (synpharyngitic)
30-40% mild proteinuria and microscopic
hematuria
Sunday, March 15, 2009

82. Presentation of
IgA Nephropathy
40-50% cases have URI with episode of gross
hematuria as presenting Sx (synpharyngitic)
30-40% mild proteinuria and microscopic
hematuria
HTN and peripheral edema rare
Sunday, March 15, 2009

83. Presentation of
IgA Nephropathy
40-50% cases have URI with episode of gross
hematuria as presenting Sx (synpharyngitic)
30-40% mild proteinuria and microscopic
hematuria
HTN and peripheral edema rare
Less commonly presents with NS
Sunday, March 15, 2009

84. Presentation of
IgA Nephropathy
40-50% cases have URI with episode of gross
hematuria as presenting Sx (synpharyngitic)
30-40% mild proteinuria and microscopic
hematuria
HTN and peripheral edema rare
Less commonly presents with NS
Cross over presentation with Henoch Schonlein
purpura(HSP), more common in children
Sunday, March 15, 2009

85. Diagnosis of
IgA Nephropathy
Sunday, March 15, 2009

86. Diagnosis of
IgA Nephropathy
Based on clinical and lab data but only can be
confirmed by renal biopsy
Sunday, March 15, 2009

87. Diagnosis of
IgA Nephropathy
Based on clinical and lab data but only can be
confirmed by renal biopsy
Often since benign course a renal biopsy not done.
Usually only if proteinuria >1g/d, HTN, edema,
decreased GFR
Sunday, March 15, 2009

88. Diagnosis of
IgA Nephropathy
Based on clinical and lab data but only can be
confirmed by renal biopsy
Often since benign course a renal biopsy not done.
Usually only if proteinuria >1g/d, HTN, edema,
decreased GFR
Skin Bx looking for IgA1 deposition in dermal
capillaries has been evaluated but unreliable
Sunday, March 15, 2009

89. Diagnosis of
IgA Nephropathy
Based on clinical and lab data but only can be
confirmed by renal biopsy
Often since benign course a renal biopsy not done.
Usually only if proteinuria >1g/d, HTN, edema,
decreased GFR
Skin Bx looking for IgA1 deposition in dermal
capillaries has been evaluated but unreliable
Plasma IgA1 elevated in 30-50%
Sunday, March 15, 2009

90. Diagnosis of
IgA Nephropathy
Based on clinical and lab data but only can be
confirmed by renal biopsy
Often since benign course a renal biopsy not done.
Usually only if proteinuria >1g/d, HTN, edema,
decreased GFR
Skin Bx looking for IgA1 deposition in dermal
capillaries has been evaluated but unreliable
Plasma IgA1 elevated in 30-50%
DDx: Thin basement membrane disease and hereditary
nephritis
Sunday, March 15, 2009

91. Pathology of IgA
Nephropathy
Sunday, March 15, 2009

92. Pathology of IgA
Nephropathy
LM:
Mesangial
expansion
increased
matrix and
cellularity
Sunday, March 15, 2009

93. Pathology of IgA
Nephropathy
Sunday, March 15, 2009

94. Pathology of IgA
Nephropathy
IF:
IgA mesangial
staining
Sunday, March 15, 2009

95. Pathology of IgA
Nephropathy
Sunday, March 15, 2009

96. Pathology of IgA
Nephropathy
EM:
Deposits in
mesangial and
paramesangial
areas
Sunday, March 15, 2009

97. Clinical Course of
IgA Nephropathy
Sunday, March 15, 2009

98. Clinical Course of
IgA Nephropathy
Kidney function progressively worsens in
~40-60%... 50% will reach ESRD after 20 yrs of
clinically apparent disease.
Sunday, March 15, 2009

99. Clinical Course of
IgA Nephropathy
Kidney function progressively worsens in
~40-60%... 50% will reach ESRD after 20 yrs of
clinically apparent disease.
<10% develop nephrotic syndrome
Sunday, March 15, 2009

100. Clinical Course of
IgA Nephropathy
Kidney function progressively worsens in
~40-60%... 50% will reach ESRD after 20 yrs of
clinically apparent disease.
<10% develop nephrotic syndrome
1/3 patients benign course with chronic
microscopic hematuria, normal serum creatinine
and <1g/day proteinuria
Sunday, March 15, 2009

101. Clinical Course of
IgA Nephropathy
Kidney function progressively worsens in
~40-60%... 50% will reach ESRD after 20 yrs of
clinically apparent disease.
<10% develop nephrotic syndrome
1/3 patients benign course with chronic
microscopic hematuria, normal serum creatinine
and <1g/day proteinuria
<10% RPGN
Sunday, March 15, 2009

102. Risk Factors for worse
prognosis with
IgA Nephropathy
Sunday, March 15, 2009

103. Risk Factors for worse
prognosis with
IgA Nephropathy
HTN
Sunday, March 15, 2009

104. Risk Factors for worse
prognosis with
IgA Nephropathy
HTN
Absence of history of macroscopic hematuria
Sunday, March 15, 2009

105. Risk Factors for worse
prognosis with
IgA Nephropathy
HTN
Absence of history of macroscopic hematuria
Persistent microscopic hematuria
Sunday, March 15, 2009

106. Risk Factors for worse
prognosis with
IgA Nephropathy
HTN
Absence of history of macroscopic hematuria
Persistent microscopic hematuria
Older age at onset
Sunday, March 15, 2009

107. Risk Factors for worse
prognosis with
IgA Nephropathy
HTN
Absence of history of macroscopic hematuria
Persistent microscopic hematuria
Older age at onset
Renal dysfunction at onset
Sunday, March 15, 2009

108. Risk Factors for worse
prognosis with
IgA Nephropathy
HTN
Absence of history of macroscopic hematuria
Persistent microscopic hematuria
Older age at onset
Renal dysfunction at onset
Proteinuria >0.5 g/day
Sunday, March 15, 2009

109. Treatment of
IgA Nephropathy
Sunday, March 15, 2009

110. Treatment of
IgA Nephropathy
Non-immunosupressive
ACEi/ ARB
Statin based cholesterol control
FISH OILS (rich in omega 3FA)
Sunday, March 15, 2009

111. Treatment of
IgA Nephropathy
Non-immunosupressive
ACEi/ ARB
Statin based cholesterol control
FISH OILS (rich in omega 3FA)
Immunosupression
Corticosteroids
Corticosteroids + cytoxan
Others: Cyclosporin, CellCept, Imuran
Sunday, March 15, 2009

112. Treatment of
IgA Nephropathy
Non-immunosupressive
ACEi/ ARB
Statin based cholesterol control
FISH OILS (rich in omega 3FA)
Immunosupression
Corticosteroids
Corticosteroids + cytoxan
Others: Cyclosporin, CellCept, Imuran
Other: IVIg, ASA, dapsone, danazol, gluten
free diet, low anigen diet, tonsillectomy
Sunday, March 15, 2009

113. Postinfectious
Glomerulonephritis
Sunday, March 15, 2009

114. Postinfectious
Glomerulonephritis
Sunday, March 15, 2009

115. Postinfectious
Glomerulonephritis
Infection is a common cause of GN and can be seen with
a variety of bacterial and viral infections.
Sunday, March 15, 2009

116. Postinfectious
Glomerulonephritis
Infection is a common cause of GN and can be seen with
a variety of bacterial and viral infections.
Poststreptococcal GN is most common and classic form
Induced by Nephritic strain of beta-hemolytic Group
A Strep
Seen after acute pharyngitis or skin infection
Sunday, March 15, 2009

117. Postinfectious
Glomerulonephritis
Infection is a common cause of GN and can be seen with
a variety of bacterial and viral infections.
Poststreptococcal GN is most common and classic form
Induced by Nephritic strain of beta-hemolytic Group
A Strep
Seen after acute pharyngitis or skin infection
Also can be seen with:
Hepatits B, Hepatitis C, malaria, syphilis,
infectious endocarditis, HIV, chronic visceral
abscess
Sunday, March 15, 2009

118. Poststreptococcal GN
Sunday, March 15, 2009

119. Poststreptococcal GN
The clinical presentation can vary from
asymptomatic, microscopic hematuria to the
full-blown acute nephritic syndrome,
characterized by red to brown urine,
proteinuria (which can reach the nephrotic
range), edema, hypertension, and acute renal
failure
Sunday, March 15, 2009

120. Poststreptococcal GN
The clinical presentation can vary from
asymptomatic, microscopic hematuria to the
full-blown acute nephritic syndrome,
characterized by red to brown urine,
proteinuria (which can reach the nephrotic
range), edema, hypertension, and acute renal
failure
Presentation may be similar to IgA Nephropathy
Sunday, March 15, 2009

121. Distinguishing PSGN
vs IgAN
Sunday, March 15, 2009

122. Distinguishing PSGN
vs IgAN
Latent period from infection until hematuria
PSGN: 10 days- pharyngitis; 21 days- impetigo
IgAN: <5 days
Sunday, March 15, 2009

123. Distinguishing PSGN
vs IgAN
Latent period from infection until hematuria
PSGN: 10 days- pharyngitis; 21 days- impetigo
IgAN: <5 days
Recurrent episodes of gross hematuria:
common in IgA nephropathy but rare in
poststreptococcal glomerulonephritis
Sunday, March 15, 2009

124. Distinguishing PSGN
vs IgAN
Latent period from infection until hematuria
PSGN: 10 days- pharyngitis; 21 days- impetigo
IgAN: <5 days
Recurrent episodes of gross hematuria:
common in IgA nephropathy but rare in
poststreptococcal glomerulonephritis
Postive serology with PSGN
ASLO (antistreptolysin O titers), anti-DNAse B,
anti-hyaluronidase
Sunday, March 15, 2009

125. Distinguishing PSGN
vs IgAN
Latent period from infection until hematuria
PSGN: 10 days- pharyngitis; 21 days- impetigo
IgAN: <5 days
Recurrent episodes of gross hematuria:
common in IgA nephropathy but rare in
poststreptococcal glomerulonephritis
Postive serology with PSGN
ASLO (antistreptolysin O titers), anti-DNAse B,
anti-hyaluronidase
Hypocomplementemia with PSGN
Sunday, March 15, 2009

126. Postinfectious GN
Pathology
Sunday, March 15, 2009

127. Postinfectious GN
Pathology
LM: Diffuse
hypercellularity
involving all
glomeruli.
Sunday, March 15, 2009

128. Postinfectious GN
Pathology
LM: Diffuse
hypercellularity
involving all
glomeruli.
Glomerular tufts
enlarged
Sunday, March 15, 2009

129. Postinfectious GN
Pathology
Sunday, March 15, 2009

130. Postinfectious GN
Pathology
EM:
characteristic
subepithelial
humps
Sunday, March 15, 2009

131. Poststreptococcal GN
Sunday, March 15, 2009

132. Poststreptococcal GN
Usually self limited
Sunday, March 15, 2009

133. Poststreptococcal GN
Usually self limited
Spontaneous recovery is the rule
Sunday, March 15, 2009

134. Poststreptococcal GN
Usually self limited
Spontaneous recovery is the rule
Rarely patients can develop HTN,
recurrent proteinuria and renal
insufficiency
Sunday, March 15, 2009

135. Poststreptococcal GN
Usually self limited
Spontaneous recovery is the rule
Rarely patients can develop HTN,
recurrent proteinuria and renal
insufficiency
Second episode is very rare
Sunday, March 15, 2009

136. Other Infectious
Causes of GN
Sunday, March 15, 2009

137. Hepatitis B related GN
Sunday, March 15, 2009

138. Hepatitis B related GN
Mainly Membranous Nephropathy
Sunday, March 15, 2009

139. Hepatitis B related GN
Mainly Membranous Nephropathy
Second most common is MPGN
Sunday, March 15, 2009

140. Hepatitis B related GN
Mainly Membranous Nephropathy
Second most common is MPGN
Pts usually carry HBsAg, HBcAg and HBeAg
Sunday, March 15, 2009

141. Hepatitis B related GN
Mainly Membranous Nephropathy
Second most common is MPGN
Pts usually carry HBsAg, HBcAg and HBeAg
Steroids are contraindicated
Sunday, March 15, 2009

142. Hepatitis B related GN
Mainly Membranous Nephropathy
Second most common is MPGN
Pts usually carry HBsAg, HBcAg and HBeAg
Steroids are contraindicated
Antiviral treatment is indicated
Sunday, March 15, 2009

143. Hepatitis C related GN
Sunday, March 15, 2009

144. Hepatitis C related GN
Typically related to cryoglobulinemia
Arthlagias, peripheral neuropathy and
purpura
Sunday, March 15, 2009

145. Hepatitis C related GN
Typically related to cryoglobulinemia
Arthlagias, peripheral neuropathy and
purpura
Hypocomplementemia
Sunday, March 15, 2009

146. Hepatitis C related GN
Typically related to cryoglobulinemia
Arthlagias, peripheral neuropathy and
purpura
Hypocomplementemia
MPGN most commonly
Sunday, March 15, 2009

147. Hepatitis C related GN
Typically related to cryoglobulinemia
Arthlagias, peripheral neuropathy and
purpura
Hypocomplementemia
MPGN most commonly
Treatment of underlying HepC with interferon
and ribavirin is typical, other
immunosuppressive treatment is controversial
Sunday, March 15, 2009

148. HIV associated
nephropathy (HIVAN)
Sunday, March 15, 2009

149. HIV associated
nephropathy (HIVAN)
Usually presents as a collapsing form of FSGS with
severe tubulointerstitial injury
Sunday, March 15, 2009

150. HIV associated
nephropathy (HIVAN)
Usually presents as a collapsing form of FSGS with
severe tubulointerstitial injury
Clinical characteristics
Severe nephrosis with massive proteinuria
Large echogenic kidneys on sonogram
Usually normotensive
Progressive renal decline to ESRD (1-4 months)
Sunday, March 15, 2009

151. HIV associated
nephropathy (HIVAN)
Usually presents as a collapsing form of FSGS with
severe tubulointerstitial injury
Clinical characteristics
Severe nephrosis with massive proteinuria
Large echogenic kidneys on sonogram
Usually normotensive
Progressive renal decline to ESRD (1-4 months)
Treatment
HAART and ACEi
Sunday, March 15, 2009

152. HIVAN Pathology
Sunday, March 15, 2009

153. HIVAN Pathology
LM: Collapsing severe FSGS
Sunday, March 15, 2009

154. HIVAN Pathology
LM: Collapsing severe FSGS
EM: TRI (tubuloreticular inclusion bodies)
Sunday, March 15, 2009

155. Lupus Nephritis
Sunday, March 15, 2009

156. Systemic Lupus
Erythematosus (SLE)
Sunday, March 15, 2009

157. Systemic Lupus
Erythematosus (SLE)
SLE predominantly effects women 10x> men
Peak incidence: age 15-40
AA 3 fold higher incidence & develop younger age
More often +anti-Sm and RNP Ab
Increased severity and mortality compared with
whites
Sunday, March 15, 2009

158. Systemic Lupus
Erythematosus (SLE)
SLE predominantly effects women 10x> men
Peak incidence: age 15-40
AA 3 fold higher incidence & develop younger age
More often +anti-Sm and RNP Ab
Increased severity and mortality compared with
whites
Children and males develop nephritis more frequently
Sunday, March 15, 2009

159. Systemic Lupus
Erythematosus (SLE)
SLE predominantly effects women 10x> men
Peak incidence: age 15-40
AA 3 fold higher incidence & develop younger age
More often +anti-Sm and RNP Ab
Increased severity and mortality compared with
whites
Children and males develop nephritis more frequently
Nephritis usually associated with high titer anti-
dsDNA, anemia, family history of SLE, and
hypocomplementia
Sunday, March 15, 2009

160. WHO Classification of
Lupus Nephritis
Sunday, March 15, 2009

161. WHO Classification of
Lupus Nephritis
Class I: Minimal mesangial LN
Sunday, March 15, 2009

162. WHO Classification of
Lupus Nephritis
Class I: Minimal mesangial LN
Class II: Mesangial proliferative LN
Sunday, March 15, 2009

163. WHO Classification of
Lupus Nephritis
Class I: Minimal mesangial LN
Class II: Mesangial proliferative LN
Class III: Focal LN (<50% glomeruli involved)
Sunday, March 15, 2009

164. WHO Classification of
Lupus Nephritis
Class I: Minimal mesangial LN
Class II: Mesangial proliferative LN
Class III: Focal LN (<50% glomeruli involved)
Class IV: Diffuse LN
Sunday, March 15, 2009

165. WHO Classification of
Lupus Nephritis
Class I: Minimal mesangial LN
Class II: Mesangial proliferative LN
Class III: Focal LN (<50% glomeruli involved)
Class IV: Diffuse LN
Class V: Membranous LN
Sunday, March 15, 2009

166. WHO Classification of
Lupus Nephritis
Class I: Minimal mesangial LN
Class II: Mesangial proliferative LN
Class III: Focal LN (<50% glomeruli involved)
Class IV: Diffuse LN
Class V: Membranous LN
Class VI: Advanced sclerotic LN (ESRD)
Sunday, March 15, 2009

167. Lupus Nephritis Pathology
Sunday, March 15, 2009

168. Lupus Nephritis Pathology
LM: Mesangial
proliferation
Sunday, March 15, 2009

169. Lupus Nephritis Pathology
LM: Mesangial
proliferation
Sunday, March 15, 2009

170. Lupus Nephritis Pathology
LM: Mesangial
proliferation
Diffuse proliferative
nephritis with “wire
loop” (thickened GBM
with immune deposits)
Sunday, March 15, 2009

171. Lupus Nephritis Pathology
Sunday, March 15, 2009

172. Lupus Nephritis Pathology
IF: massive “lumpy
bumpy” IgG
distribution
Sunday, March 15, 2009

173. Lupus Nephritis Pathology
IF: massive “lumpy
bumpy” IgG
distribution
EM: classic
subENDOthelial
deposits (Class III
and IV) and TRI
Sunday, March 15, 2009

174. Treatment of Lupus
Nephritis
Sunday, March 15, 2009

175. Treatment of Lupus
Nephritis
Class I and II LN have excellent renal prognosis
and no specific therapy indicated
Sunday, March 15, 2009

176. Treatment of Lupus
Nephritis
Class I and II LN have excellent renal prognosis
and no specific therapy indicated
Proliferative LN (Class IV) : Poorest prognosis
Treatment of choice: Pulse Solumedrol followed
by IV pulse Cytoxan and po Prednisone
Other agents: Imuran, CellCept, Cyclosporin
Sunday, March 15, 2009

177. Treatment of Lupus
Nephritis
Class I and II LN have excellent renal prognosis
and no specific therapy indicated
Proliferative LN (Class IV) : Poorest prognosis
Treatment of choice: Pulse Solumedrol followed
by IV pulse Cytoxan and po Prednisone
Other agents: Imuran, CellCept, Cyclosporin
Membranous LN (Class V)
No clear consensus; attempt immunosuppresion
as per idiopathic MN
Sunday, March 15, 2009

178. Crescentic
Glomerulonephritis
Sunday, March 15, 2009

179. Rapidly Progressive
Glomerulonephritis (RPGN)
Sunday, March 15, 2009

180. Rapidly Progressive
Glomerulonephritis (RPGN)
Severe form of GN
Sunday, March 15, 2009

181. Rapidly Progressive
Glomerulonephritis (RPGN)
Severe form of GN
Progression to ESRD in weeks to months
Sunday, March 15, 2009

182. Rapidly Progressive
Glomerulonephritis (RPGN)
Severe form of GN
Progression to ESRD in weeks to months
Characterized by crescentic lesions
Severity of disease corresponds to degree of
crescent
Crescent formation caused by severe injury to
glomerular capillary wall
Crescents may be more acute (cellular) or
older (fibrotic)….. or mixed (fibrocellular)
Sunday, March 15, 2009

183. Crescentic
Glomerulonephritis
Sunday, March 15, 2009

184. Sunday, March 15, 2009

185. Sunday, March 15, 2009

186. Types of Crescentic
Glomerulonephritis
Sunday, March 15, 2009

187. Types of Crescentic
Glomerulonephritis
Anti-GBM
Goodpasture’s syndrome; Anti-GBM Disease
Sunday, March 15, 2009

188. Types of Crescentic
Glomerulonephritis
Anti-GBM
Goodpasture’s syndrome; Anti-GBM Disease
Immune mediated
IgA N, postinfectious GN, SLE, Cryoglobulinemia
Sunday, March 15, 2009

189. Types of Crescentic
Glomerulonephritis
Anti-GBM
Goodpasture’s syndrome; Anti-GBM Disease
Immune mediated
IgA N, postinfectious GN, SLE, Cryoglobulinemia
Pauci-immune
RPGN with little to no immune deposits on IF/EM
Majority: ‘ANCA associated vasculitis’
ANCA= Anti-Neutrophilic Cytoplasmic Antibody
Wegner’s granulomatosis, microscopic
polyangiitis, Churg-Strauss syndrome
Sunday, March 15, 2009

190. Clinical presentation
of RPGN
Sunday, March 15, 2009

191. Clinical presentation
of RPGN
Most commonly insidious: fatigue and /or edema
Sunday, March 15, 2009

192. Clinical presentation
of RPGN
Most commonly insidious: fatigue and /or edema
Renal insufficiency seen at presentation
Sunday, March 15, 2009

193. Clinical presentation
of RPGN
Most commonly insidious: fatigue and /or edema
Renal insufficiency seen at presentation
Urinalysis:
RBCs, RBC casts, varying proteinuria (NS unusual)
Sunday, March 15, 2009

194. Clinical presentation
of RPGN
Most commonly insidious: fatigue and /or edema
Renal insufficiency seen at presentation
Urinalysis:
RBCs, RBC casts, varying proteinuria (NS unusual)
Systemic complaints
Pauci-immune ANCA positive or negative
AntiGBM- Goodpasture’s
Immune complex disease- i.e.. SLE
Sunday, March 15, 2009

195. Goodpasture’s
Syndrome
Sunday, March 15, 2009

196. Goodpasture’s
Syndrome
Sunday, March 15, 2009

197. Goodpasture’s
Syndrome
First used term in 1957 after a report detailing 9 pts
with pulmonary renal syndrome first described by
Goodpasture in 1919.
Sunday, March 15, 2009

198. Goodpasture’s
Syndrome
First used term in 1957 after a report detailing 9 pts
with pulmonary renal syndrome first described by
Goodpasture in 1919.
Autoimmune disease to the antigen found on the alpha3
chain of type IV collagen of the GBM
Sunday, March 15, 2009

199. Goodpasture’s
Syndrome
First used term in 1957 after a report detailing 9 pts
with pulmonary renal syndrome first described by
Goodpasture in 1919.
Autoimmune disease to the antigen found on the alpha3
chain of type IV collagen of the GBM
The syndrome describes combination of:
RPGN
Pulmonary hemorrhage
Anti-GBM Ab
Sunday, March 15, 2009

200. Goodpasture’s
Syndrome
First used term in 1957 after a report detailing 9 pts
with pulmonary renal syndrome first described by
Goodpasture in 1919.
Autoimmune disease to the antigen found on the alpha3
chain of type IV collagen of the GBM
The syndrome describes combination of:
RPGN
Pulmonary hemorrhage
Anti-GBM Ab
anti-GBM disease refers to any pt with the Ab
regardless of clinical features
Sunday, March 15, 2009

201. Goodpasture’s
Syndrome
Sunday, March 15, 2009

202. Goodpasture’s
Syndrome
Bimodal age distribution: 3rd and 6th decades
Sunday, March 15, 2009

203. Goodpasture’s
Syndrome
Bimodal age distribution: 3rd and 6th decades
Males > Female; predominantly white race
Sunday, March 15, 2009

204. Goodpasture’s
Syndrome
Bimodal age distribution: 3rd and 6th decades
Males > Female; predominantly white race
Most have RPGN and lung hemorrhage
Sunday, March 15, 2009

205. Goodpasture’s
Syndrome
Bimodal age distribution: 3rd and 6th decades
Males > Female; predominantly white race
Most have RPGN and lung hemorrhage
1/3 isolated GN
Sunday, March 15, 2009

206. Goodpasture’s
Syndrome
Bimodal age distribution: 3rd and 6th decades
Males > Female; predominantly white race
Most have RPGN and lung hemorrhage
1/3 isolated GN
Rarely isolated lung hemorrhage without renal
disease
Sunday, March 15, 2009

207. Goodpasture’s
Syndrome
Bimodal age distribution: 3rd and 6th decades
Males > Female; predominantly white race
Most have RPGN and lung hemorrhage
1/3 isolated GN
Rarely isolated lung hemorrhage without renal
disease
Malaise, fatigue, weight loss are the most common
systemic features
Sunday, March 15, 2009

208. Goodpasture’s
Syndrome
Sunday, March 15, 2009

209. Goodpasture’s
Syndrome
Pulmonary hemorrhage
occurs in 2/3rds; more common in younger men
May proceed renal disease
Triggered by smoking, toxins, sepsis, fluid overload
Sunday, March 15, 2009

210. Goodpasture’s
Syndrome
Pulmonary hemorrhage
occurs in 2/3rds; more common in younger men
May proceed renal disease
Triggered by smoking, toxins, sepsis, fluid overload
Renal Disease
Most commonly acute renal failure with RPGN
Urine micro: RBC, RBC casts, mild-mod proteinuria
(nephrotic syndrome rare)
HTN and oliguria are late features
Rarely isolated hematuria or mild renal dysfunction
Sunday, March 15, 2009

211. Goodpasture’s Syndrome
Pathology
Sunday, March 15, 2009

212. Goodpasture’s Syndrome
Pathology
LM: diffuse
crescentic
glomerulonephritis
Sunday, March 15, 2009

213. Goodpasture’s Syndrome
Pathology
LM: diffuse
crescentic
glomerulonephritis
Prominent
interstitial
cellular
infiltrate
Sunday, March 15, 2009

214. Goodpasture’s Syndrome
Pathology
Sunday, March 15, 2009

215. Goodpasture’s Syndrome
Pathology
IF: Classic
linear IgG and
C3 along the GBM
Sunday, March 15, 2009

216. Goodpasture’s Syndrome
Treatment
Sunday, March 15, 2009

217. Goodpasture’s Syndrome
Treatment
Untreated: Fatal
Sunday, March 15, 2009

218. Goodpasture’s Syndrome
Treatment
Untreated: Fatal
Combination therapy: Plasma exchange, Cytoxan and
Corticosteroids
Plasmapharesis: plasma exchange is used to
remove circulating anti-GBM Ab
Cytoxan: prevents further Ab synthesis
Steroids: Pulse IV Solumedrol followed by
Prednisone
Sunday, March 15, 2009

219. Goodpasture’s Syndrome
Treatment
Untreated: Fatal
Combination therapy: Plasma exchange, Cytoxan and
Corticosteroids
Plasmapharesis: plasma exchange is used to
remove circulating anti-GBM Ab
Cytoxan: prevents further Ab synthesis
Steroids: Pulse IV Solumedrol followed by
Prednisone
Prognosis depends on the severity of disease upon
presentation. If dialysis is need up to
presentation, renal recovery is rare
Sunday, March 15, 2009

220. ANCA-associated
Vasculitis
Sunday, March 15, 2009

221. Vasculitis
Sunday, March 15, 2009

222. ANCA
Sunday, March 15, 2009

223. Wegner’s
Granulomatosis
Sunday, March 15, 2009

224. Wegner’s
Granulomatosis
Systemic vasculitis medium and small size
arteries
Sunday, March 15, 2009

225. Wegner’s
Granulomatosis
Systemic vasculitis medium and small size
arteries
90 % ANCA positive
70-80% c-ANCA + Anti-Proteinase 3 (PR3)
10-15% p-ANCA + Anti-Myeloperoxidase (MPO)
Sunday, March 15, 2009

226. Wegner’s
Granulomatosis
Systemic vasculitis medium and small size
arteries
90 % ANCA positive
70-80% c-ANCA + Anti-Proteinase 3 (PR3)
10-15% p-ANCA + Anti-Myeloperoxidase (MPO)
Classic WG: involvement of the upper and lower
respiratory tract and kidneys
Sunday, March 15, 2009

227. Wegner’s
Granulomatosis
Manifestations
Sunday, March 15, 2009

228. Wegner’s
Granulomatosis
Manifestations
In addition to renal and lung….:
Joints: myalgias, arthalgias, arthritis
Eyes: conjunctivitis, corneal ulcers
Skin: palpable purpura
Nervous system: mononeuritis multiplex
Less commonly: GI, heart, GU tract, thyroid
High incidence of DVT
Sunday, March 15, 2009

229. Wegner’s
Granulomatosis
Manifestations
In addition to renal and lung….:
Joints: myalgias, arthalgias, arthritis
Eyes: conjunctivitis, corneal ulcers
Skin: palpable purpura
Nervous system: mononeuritis multiplex
Less commonly: GI, heart, GU tract, thyroid
High incidence of DVT
“ELKS” = Eyes, Lungs, Kidneys, Sinsus involvement
Sunday, March 15, 2009

230. Wegner’s Granulomatosis
Presentation
Sunday, March 15, 2009

231. Wegner’s Granulomatosis
Presentation
The most common presenting symptoms include:
persistent rhinorrhea, purulent/bloody
nasal discharge, oral and/or nasal ulcers,
polyarthralgias, myalgias, or sinus pain.
Sunday, March 15, 2009

232. Wegner’s Granulomatosis
Presentation
The most common presenting symptoms include:
persistent rhinorrhea, purulent/bloody
nasal discharge, oral and/or nasal ulcers,
polyarthralgias, myalgias, or sinus pain.
Less common symptoms of upper airway
involvement:
hoarseness, stridor, earache, both
conductive and sensorineural hearing loss,
or otorrhea
Sunday, March 15, 2009

233. Wegner’s Granulomatosis
Sunday, March 15, 2009

234. Wegner’s Granulomatosis
Pulmonary Imaging
findings:
Nodules (which may
cavitate)
Alveolar opacities
Pleural opacities
Diffuse hazy
opacities (which may
reflect alveolar
hemorrhage)
Sunday, March 15, 2009

235. Wegner’s Granulomatosis
Diagnosis
Sunday, March 15, 2009

236. Wegner’s Granulomatosis
Diagnosis
The four clinical criteria are:

Nasal or oral inflammation (painful or
1.
painless oral ulcers or purulent or bloody
nasal discharge)
Abnormal chest radiograph showing nodules,
2.
fixed infiltrates, or cavities
Abnormal urinary sediment (microscopic
3.
hematuria with or without red cell casts)
Granulomatous inflammation on biopsy of an
4.
artery or perivascular area
Sunday, March 15, 2009

237. Wegner’s Granulomatosis
Diagnosis Cont.
Sunday, March 15, 2009

238. Wegner’s Granulomatosis
Diagnosis Cont.
Labs: leukocytosis, thrombocytosis, anemia and
increased ESR, normocomplementemia
Sunday, March 15, 2009

239. Wegner’s Granulomatosis
Diagnosis Cont.
Labs: leukocytosis, thrombocytosis, anemia and
increased ESR, normocomplementemia
ANCA
Most commonly C-ANCA positive (Anti-Proteinase 3)
Sunday, March 15, 2009

240. Wegner’s Granulomatosis
Diagnosis Cont.
Labs: leukocytosis, thrombocytosis, anemia and
increased ESR, normocomplementemia
ANCA
Most commonly C-ANCA positive (Anti-Proteinase 3)
Biopsy is necessary for confirmation of diagnosis
Skin, pulmonary Bx.. or…
Renal biopsy: segmental necrotizing GN
Granulomas
Sunday, March 15, 2009

241. Wegner’s Granulomatosis
Treatment
Sunday, March 15, 2009

242. Wegner’s Granulomatosis
Treatment
Treatment of choice:
Cytoxan (1.5-2 mg/kg) and Prednisone (1mg/kg)
Daily until remission (usually atleast 3-6 months)
Sunday, March 15, 2009

243. Wegner’s Granulomatosis
Treatment
Treatment of choice:
Cytoxan (1.5-2 mg/kg) and Prednisone (1mg/kg)
Daily until remission (usually atleast 3-6 months)
Alternative Tx choices:
IV monthly Cytoxan
Methotrexate: best for non-renal WG
Sunday, March 15, 2009

244. Wegner’s Granulomatosis
Treatment
Treatment of choice:
Cytoxan (1.5-2 mg/kg) and Prednisone (1mg/kg)
Daily until remission (usually atleast 3-6 months)
Alternative Tx choices:
IV monthly Cytoxan
Methotrexate: best for non-renal WG
Maintenance therapy once remission reached:
Switch cytoxan to Imuran or MTX
Taper off Prednisone
Sunday, March 15, 2009

245. Wegner’s Granulomatosis
Prognosis
Sunday, March 15, 2009

246. Wegner’s Granulomatosis
Prognosis
Natural History: Untreated fatal: 90% mortality 2 years
Sunday, March 15, 2009

247. Wegner’s Granulomatosis
Prognosis
Natural History: Untreated fatal: 90% mortality 2 years
Otherwise prognosis is a consequence of:
Irreversible organ damage prior to Tx
SE of immunosuppression
Glucocorticoid toxicity
Superimposed infections
Secondary malignancies
Sunday, March 15, 2009

248. Wegner’s Granulomatosis
Prognosis
Natural History: Untreated fatal: 90% mortality 2 years
Otherwise prognosis is a consequence of:
Irreversible organ damage prior to Tx
SE of immunosuppression
Glucocorticoid toxicity
Superimposed infections
Secondary malignancies
Renal outcome depends upon severity of disease at
presentation
Sunday, March 15, 2009

249. Microscopic
Polyangiitis
Sunday, March 15, 2009

250. Microscopic
Polyangiitis
Overlaps with Wegner’s granulomatosis
Sunday, March 15, 2009

251. Microscopic
Polyangiitis
Overlaps with Wegner’s granulomatosis
More often “renal-limited” with findings
indistinguishable from WG
Sunday, March 15, 2009

252. Microscopic
Polyangiitis
Overlaps with Wegner’s granulomatosis
More often “renal-limited” with findings
indistinguishable from WG
Absence of granulomatous inflammation
Sunday, March 15, 2009

253. Microscopic
Polyangiitis
Overlaps with Wegner’s granulomatosis
More often “renal-limited” with findings
indistinguishable from WG
Absence of granulomatous inflammation
70% ANCA positive but more often p-ANCA (anti
MPO)
Sunday, March 15, 2009

254. Microscopic
Polyangiitis
Overlaps with Wegner’s granulomatosis
More often “renal-limited” with findings
indistinguishable from WG
Absence of granulomatous inflammation
70% ANCA positive but more often p-ANCA (anti
MPO)
Treatment same as for WG
Sunday, March 15, 2009

255. Microscopic
Polyangiitis
Overlaps with Wegner’s granulomatosis
More often “renal-limited” with findings
indistinguishable from WG
Absence of granulomatous inflammation
70% ANCA positive but more often p-ANCA (anti
MPO)
Treatment same as for WG
More often there are relapses with WG
Sunday, March 15, 2009

256. Churg-Strauss
Syndrome
Sunday, March 15, 2009

257. Churg-Strauss
Syndrome
AKA: Allergic granulomatosis and angiitis
Sunday, March 15, 2009

258. Churg-Strauss
Syndrome
AKA: Allergic granulomatosis and angiitis
ANCA + ~50%, most commonly pANCA +
Sunday, March 15, 2009

259. Churg-Strauss
Syndrome
AKA: Allergic granulomatosis and angiitis
ANCA + ~50%, most commonly pANCA +
Multisystemic disorder
Allergic rhinitis
Asthma- cardinal feature 95% occurrence
Peripheral eosinophilia
Sunday, March 15, 2009

260. Churg-Strauss
Syndrome
AKA: Allergic granulomatosis and angiitis
ANCA + ~50%, most commonly pANCA +
Multisystemic disorder
Allergic rhinitis
Asthma- cardinal feature 95% occurrence
Peripheral eosinophilia
All organ systems can be involved
Most commonly: lungs and skin
Also: Cardiac, Kidneys, GI and CNS
Sunday, March 15, 2009

261. Churg-Strauss Syndrome
Clinical Features
Sunday, March 15, 2009

262. Churg-Strauss Syndrome
Clinical Features
Prodromal phase
2nd-3rd decade of life; asthma and allergic
rhinitis
Sunday, March 15, 2009

263. Churg-Strauss Syndrome
Clinical Features
Prodromal phase
2nd-3rd decade of life; asthma and allergic
rhinitis
Eosinophilic phase
Peripheral blood eosinophilia and eosinophilic
infiltrates of organs (most commonly lung)
Sunday, March 15, 2009

264. Churg-Strauss Syndrome
Clinical Features
Prodromal phase
2nd-3rd decade of life; asthma and allergic
rhinitis
Eosinophilic phase
Peripheral blood eosinophilia and eosinophilic
infiltrates of organs (most commonly lung)
Vasculitic phase
3rd-4th decade of life; small-medium size
systemic vasculitis
Sunday, March 15, 2009

265. Churg-Strauss Syndrome
Renal Manifestations
Sunday, March 15, 2009

266. Churg-Strauss Syndrome
Renal Manifestations
Similar, but less severe than Wegner’s
Granulomatosis typically
Sunday, March 15, 2009

267. Churg-Strauss Syndrome
Renal Manifestations
Similar, but less severe than Wegner’s
Granulomatosis typically
Best renal prognosis of all the causes of
RPGN with <10% progression to ESRD
Sunday, March 15, 2009

268. Churg-Strauss Syndrome
Renal Manifestations
Similar, but less severe than Wegner’s
Granulomatosis typically
Best renal prognosis of all the causes of
RPGN with <10% progression to ESRD
Systemic HTN common
Sunday, March 15, 2009

269. Churg-Strauss Syndrome
Renal Manifestations
Similar, but less severe than Wegner’s
Granulomatosis typically
Best renal prognosis of all the causes of
RPGN with <10% progression to ESRD
Systemic HTN common
Renal infarction can be seen
Sunday, March 15, 2009

270. Brief Urine
Microscopy
Review
Sunday, March 15, 2009

271. Urine Microscopy
Review
Casts
Urinary casts are formed only in the distal
convoluted tubule (DCT) or the collecting duct
(distal nephron). The proximal convoluted tubule
(PCT) and loop of Henle are not locations for
cast formation
Hyaline casts
not indicative of disease
Hyaline casts are composed primarily of a
mucoprotein (Tamm-Horsfall protein) secreted by
tubule cells
Sunday, March 15, 2009

272. Urinary Casts
The Tamm-Horsfall
protein secretion
(green dots) is
illustrated in the
diagram below,
forming a hyaline
cast in the
collecting duct
Sunday, March 15, 2009

273. Hyaline Casts
Hyaline casts, which
appear very pale and
slightly refractile,
are common findings
in urine.
Sunday, March 15, 2009

274. RBC Casts
Glomerular
inflammation with
leakage of RBC's to
produce a red blood
cell cast is shown in
the diagram
Sunday, March 15, 2009

275. RBC Casts
Red cell casts — The
finding of red
cell casts, even
if only one is
seen, is virtually
diagnostic of
glomerulonephritis
Sunday, March 15, 2009

276. WBC Casts
White cell casts — The
presence of white
cell casts and pyuria
alone is most
consistent with a
tubulointerstitial
disease or acute
pyelonephritis
Sunday, March 15, 2009

277. Urine Microscopy Casts
Epithelial cell casts — Acute tubular necrosis and
acute glomerulonephritis, disorders in which
epithelial cells are desquamated, may be
associated with epithelial cell casts
Fatty casts — Among patients with significant
proteinuria, the degeneration of cells within
epithelial casts may result in a fatty cast
Sunday, March 15, 2009

278. Polarized Light Oval Fat Bodies
appearance “Maltese Cross”
Sunday, March 15, 2009

279. Granular Casts
Granular casts — When
cellular casts or
aggregated proteins
remain in the nephron
for some time before
they are flushed into
the bladder urine,
the cells may
degenerate to become
a coarsely granular
cast and later a
finely granular cast
Sunday, March 15, 2009

280. Waxy Casts
Waxy casts —thought to
be the last stage of
the degeneration of a
granular cast. Since
this degenerative
process is probably
slow, it is most
likely observed in
nephrons with very
diminished flow.
Therefore most
consistent with the
presence of advanced
renal failure
Sunday, March 15, 2009

281. Urine Microscopy Casts
Sunday, March 15, 2009

282. Case Presentation
Sunday, March 15, 2009

283. Case Presentation
30 yr old white male
athlete
CC: Elevated
Creatinine
Sunday, March 15, 2009

284. What do you want
next?
Past Medical History
Family History
Social History
Medications
Physical Exam
Anything Else?
Sunday, March 15, 2009

285. History
HPI:Recurrent sinus
infections. Some fatigue
limiting his physical
activity. Weight loss 10 lbs
over last couple months
PMHx: none
Social Hx: Single, Denies
tobacco or illicit drug use,
Social EtOH
Family Hx: No Kidney
Disease, ESRD
Medications: Zithromax
Sunday, March 15, 2009

286. Physical Exam
VS: BP 144/86 mmHg P 96 R 14
HEENT: NCAT OP lesion palate
Neck: Supple no JVD no bruits
Chest: CTA B/L
Cor: S1 S2 RRR no M/R/G
Abd: Soft NT ND +BS, no HSM
Ext: no edema
Skin: no rash
Anything else?
Sunday, March 15, 2009

287. Labs
What do you want to order?
Sunday, March 15, 2009

288. Lab Values
CBC: WBC 7.6 Hb 10.9 PLT 415
CMP: Na 138 K 4.3 Cl 108 HCO3 23
BUN 41 Creat 3.4 TBili 0.6 AST 22
ALT 25 AlkP 106 TP 6.2 Alb 3.0
Cholesterol: Chol 222 HDL 29 LDL 168
UA Dip: +1 protein, +2 blood, no LE
or nitrates
Want anything else?
Sunday, March 15, 2009

289. Other Tests
to consider
Hepatitis Panel
Compliments, ANA, c-ANCA, p-ANCA,
anti-GBM, ASLO, HIV
24 Hour urine Creatinine Clearance
and total proteinuria (U TP/Creat)
CXR
Sunday, March 15, 2009

290. 24 Hour urine
collection
Creatinine
Clearance 49 ml/min
Total proteinuria:
1,890 mg
Sunday, March 15, 2009

291. What next?
Sunday, March 15, 2009

292. Renal
Biopsy!
Sunday, March 15, 2009

293. Chest XRAY
Sunday, March 15, 2009

294. Biopsy
Sunday, March 15, 2009

295. Serology Findings
C3 / C4 / CH50 WNL
Hepatitis Panel negative
HIV negative
c-ANCA 1:640 p-ANCA negative
ANA negative
anti-GBM negative
ASLO negative
Sunday, March 15, 2009

296. Diagnosis?
Sunday, March 15, 2009

297. Wegner’s
Granulomatosis
Sunday, March 15, 2009

298. What Should We do Next?
How Should we Treat?
What is the prognosis?
Sunday, March 15, 2009

299. FIN
Simon Prince, DO, FACP, FASN
Assistant Professor of Medicine;
NYU School of Medicine
email: sprince@nsneph.com
www.nsneph.blogspot.com
Sunday, March 15, 2009