Interpretation of renal biopsy

1. INTERPRETATION OF
RENAL BIOPSY
Presenter :Dr.Revathi Krishnamurthy
Moderator : Dr.Rajasekhar.K.S

2. ANATOMY
• The kidneys are a pair of excretory
organs situated retroperitoneally
• Within the perirenal space, which
contains abundant fat & is enclosed
by the anterior and posterior layers
of renal fascia, known as Gerota’s
fascia

3. ANATOMY
Each kidney is bean-shaped,
composed of :
• Poles : Upper & Lower
• Borders : Medial & Lateral
• Surfaces : Anterior & Posterior
Location : T12 to L3

4. HISTORY
• 1951 : Percutaneous renal biopsy, based on the use of an
aspiration needle and the patient in the sitting position was first
described by Iversen and Brun
• 1954 : Kark and Muehrcke described the use of the cutting
Franklin-modified Vim-Silverman needle on patients in the
prone position, with a substantial improvement in the rate of
success
• Recent widespread availability of real time imaging using
ultrasound and Computerised Tomography (CT) scanning have
improved the safety of the procedure and also aid in the use of
biopsy guns

5. Kidney biopsy is currently done for three major reasons :
• To establish the pathologic diagnosis
• To provide insight into the treatment options
• To provide prognostic information or gauge response to
therapy

6. INDICATIONS
• Nephrotic syndrome
• Acute renal failure
• Chronic renal failure
• Hematuria
• Asymptomatic proteinuria
• Transplant

7. RELATIVE CONTRA-INDICATIONS
Kidney status Patient status
• Polycystic diseases of kidney • Uncontrolled bleeding
diathesis
• Solitary kidney • Uncontrolled hypertension
• Pyelonephritis/ Perirenal
abscess
• Hypotension
• Hydronephrosis • Morbid obesity
• Atrophic/ small kidneys(<8cm) • Vascular AV fistula
• Renal neoplasms • Severe anemia
• Uremia
• Un co-operative patient

8. PROCEDURE
Most percutaneous biopsies are performed under ultrasound or CT
guidance
Pre-requisites :
• Informed written consent
• Blood coagulation tests
• Blood grouping & typing
• Cross matching
• Recording patient’s vital signs
• Placing intravenous line
• Employing appropriate imaging method to visualise the kidneys

9. Imaging :
• Real-time imaging of the kidney during insertion of the
biopsy needle is the preferred method for performing a
percutaneous biopsy
• Several imaging tools can be used including renal ultrasound
with colour Doppler, CT & Magnetic Resonance Imaging
(MRI)
• Advantage : Visualisation of the biopsy needle as it passes
through the skin into the kidney

10. Biopsy needle :
• Spring loaded
• Size :18-gauge needle
• A variety of these devices are available ; in general these are
easier to use than manual needles (ex:Vim Silverman)
• The choice of needle size may vary and is based on technical
needs and skill of the operator
• In general, it is a reasonable size for obtaining adequate tissue in
most patients without increased risk of hemorrhage

11. Vim Silverman needle
Obturator
Outer sheath
Cutting prongs

12. Automatic spring-loaded biopsy gun

13. • Automatic biopsy guns perform better on direct comparisons
• In a randomized study comparing manual needle and
automated biopsy guns, both techniques gave adequate tissue
samples, but bleeding was more with manual needle
• Another study showed that the need for re-biopsy, large
hematomas, post-procedure vascular intervention and fall in
hemoglobin over next 24 hour all were significantly more
with blind biopsy technique

14. PROCEDURE – NATIVE KIDNEY
• Patient is placed in prone position
• Skin is marked after imaging the kidney and identifying the lower
pole, where the biopsy needle will be inserted
• Aseptic precaution of the skin is employed
• The skin & subcutaneous tissues are anaesthetized and a small
incision is made in the skin
• The patient takes a breath and holds and the needle is positioned in
the kidney

15. PROCEDURE – TRANSPLANT KIDNEY
• The pre-biospy evaluation, imaging and equipment are identical
to those for native biopsy
• However, because the transplanted kidney is in the pelvis, the
patient does not have to lie prone
• It is generally easier and standard ultrasound is sufficient
because the transplanted kidney is extraperitoneal, relatively
superficial and often palpable on physical examination

16. Other techniques :
• Transjugular
• Laparoscopic
• Open surgical approach

17. • 2 cores of tissue are obtained whenever possible, to provide
an adequate sample for light, immunofluorescence and
electron microscopy
• Light microscopy  First core
• Immunofluorescence
• Electron microscopy
Second core

18. Whenever possible, demonstration of sufficient tissue
including at least seven glomeruli should be ascertained at the
bedside using low-power dissecting microscope

19. Immediately after removal of
tissue, the specimen should be
examined under a dissecting
microscope to identify the
presence of glomeruli

20. When direct glomerular visualisation
is not available
• EM – 1mm cubes from ends of both
cores
• Remaining tissue can be cut in half
by cross-sectioning
• LM – Larger two pieces
• IF – Smaller two pieces

21. Post biopsy :
• Observe the patient for complications
• Especially bleeding – minimum 4 hours
• Monitor vital signs
• Monitor for severe back, flank or abdominal pain and gross
hematuria
• Serial haemoglobin and haematocrit should be monitored

22. HANDLING OF TISSUE
• Handle with great care in order to avoid introducing artifacts
• Keep moist with a small amount of cold normal saline solution
• Manipulation is best achieved with a small wooden stick

23. Processing of Specimens
Light microscopy :
Fixatives :
• 10% neutral buffered formalin
• Alcoholic Bouin’s
• Duboscq Brazil
Embedding : Paraffin

24. Serial thin sections (2-3µ) should be
cut and mounted on consecutively
numbered slides

25. Stains
Hematoxylin & Eosin : (H&E)
• Glomerular : Exudative lesions
• Tubular : Epithelial damage
• Interstitial : Edema, Inflammation
• Vascular : Inflammation

26. Periodic Acid Schiff reaction :
• Glomerular : GBM, capillary wall collapse
• Hyalinosis
• Sclerosis
• Mesangial cellularity , matrix increase
• Tubules : Protein droplets, tubular basement membrane
• Vascular :Hyaline arteriosclerosis

27. Methenamine-silver (Jones stain) :
• Glomerular : GBM spikes, double contour
• Breaks in GBM
• Tubular :Tubulitis
• Interstitial : Fibrosis

28. Masson Trichrome :
• Glomerular : Immune deposits
• Thrombi
• Fibrin
• Platelets
• Tubular :Tubular atrophy
• Interstitial : Fibrosis

29. Immunofluorescence microscopy (IF):
• Tissues can be transported to the laboratory either :
1. Fresh ( saline-soaked gauze) or
2. Zeus or Michael medium
• Serial sections should be cut at 3-4 µ in a cryostat
• Photographic records should be kept for all positive findings
because the fluorescence fades over time

30. Immunoperoxidase (IP):
Done when :
• Frozen tissue is not available
• Glomeruli are not present on frozen sections

31. Advantages of IP over IF :
• Frozen tissue & IF microscope attachment are not necessary
• Sections are permanent
• No special arrangements for collection & storage of tissue is
needed
• Techniques can be applied retrospectively to renal biopsy
specimens stored in paraffin for many years

32. Electron microscopy :
 Fixatives :
1. 3% phosphate-buffered glutaraldehyde
2. 2.5% glutaraldehyde in a cacodylate buffer
 Postfixation in 1% osmium tetroxide is recommended
Tissue should be cut into fragments no larger than 1x1x1 mm
 If no glomeruli present  Tissue can be reprocessed from the
paraffin block

33. Glossary of descriptive terms
• Focal  Involving some glomeruli
• Diffuse  Involving all glomeruli
• Segmental  Involving part of glomerular tuft
• Global  Involving total glomerular tuft
• Lobular  Hypersegmentation of normal lobular
appearance of capillary loop architecture
due to endocapillary proliferation
• Nodular  Relatively acellular areas of mesangial
matrix

34. • Glomerulosclerosis Increased collagenous ECM expanding
mesangium, occluding the capillary
lumen or forming adhesions to
Bowman`s capsule
• Crescent  Proliferation of parietal epithelial
cells, podocytes, infiltrating inflammatory
cells.
>2 cell layer in Bowman`s space
• Spikes  Projections of glomerular BM intervening
between subepithelial immune deposits
• Hyalinosis  Descriptive of glassy smooth appearing
acellular material

35. • Mesangial area  Stalk region of capillary loop with
mesangial cells surrounded by matrix
• Mesangial
hypercellularity  4 or more nuclei in a
peripheral mesangial segment
• Subepithelial  Between visceral epithelial cells and GBM
• Subendothelial  Between endothelial cells and GBM
• Tram-track  Double contour of GBM due to deposits

36. INTERPRETATION OF RENAL
BIOPSY
Renal biopsy specimens should only be examined when the
pathologist knows :
• Age
• Sex of the person biopsied
• Clinical indication

37. The best approach to achieve an accurate pathologic diagnosis
is to recognise the patterns of injury found in each of the four
compartments of the kidney :
• Glomeruli
• Tubules
• Interstitium
• Vessels

38. GLOMERULAR DISEASES

39. Structure of the Glomerulus

41. Glomerular capillary wall
Electron microscopy

42. Glomerular diseases associated with
Nephrotic syndrome and Proteinuria
 Minimal Change Disease
 Focal Segmental Glomerulosclerosis
 Membranous Nephropathy
 C1q Nephropathy

43. Minimal Change Disease :
• Light microscopy  Glomeruli appear virtually normal
• Electron microscopy  Effacement of foot processes of
visceral epithelial cells
PAS, x200
No pathological abnormalities
PAS, x400Electron microscopy

44. Focal Segmental Glomerulosclerosis : (FSGS)
Clinically manifests by :
• Acute or subacute onset of nephrotic syndrome or
• Non-nephrotic proteinuria
• Hypertension
• Microscopic hematuria
• Azotemia

45. Characterised by :
• Sclerosis of some, but not all glomeruli  Focal
• In the affected glomeruli, only a portion
of the capillary tuft is involved  Segmental
By light microscopy, the lesions may involve only a minority
of the glomeruli and may be missed if the biopsy specimen
contains an insufficient number of glomeruli

46. FSGS Not Otherwise Specified :
• Most common type
• No specific distinguishing features
• Diagnosed by exclusion of specific subtypes
PAS – Low power
Segmental sclerosis in one of the thee glomeruli
PAS – High power
Segmental obliteration of glomerular tuft by sclerosis and
hyalinosis
PAS – High power
Synechial attachment of glomerular tuft to Bowman’s capsule

47. Immunofluorescence microscopy
Segmental lesions often stain for :
• IgM
• C3

48. Electron microscopy :
• Diffuse effacement of foot processes – both sclerotic and
non-sclerotic areas
• Focal detachment of epithelial cells & denudation of the
underlying GBM

49. Collapsing variant :
• Characterised by retraction and/or collapse of the entire
glomerular tuft
• With or without additional FSGS lesions
• Prominent tubular injury with formation of microcysts
• Most characteristic lesion of HIV-associated nephropathy
Silver methenamine stain - 40x

50. Electron microscopy
Endothelial tubulo-reticular body

51. Glomerular tip lesion :
• Tip changes develop as
a consequence of temporary
prolapse of the glomerular tuft
into the opening of the tubule
• Adhesion of basement
membrane of tuft to that of
the Bowman’s capsule in the
vicinity of tubular opening
• Initially foamy macrophages
appear in the capillary loops,
which are later replaced by
sclerosed material

52. Cellular variant :
• Focal and segmental glomerular hypercellularity
• Affect the peripheral tufts (but lack characteristics of tip
lesion)
• Affected segments have expanded appearance
PAS, x200

53. Perihilar variant :
• >50% of the lesions involve
perihilar segment
• No collapsing lesions
• Glomerulomegaly

54. Membranous Nephropathy
• The defining features are proteinuria associated with a
spectrum of glomerular capillary wall alterations resulting
from the formation of subepithelial immune deposits
• 75% cases are primary
• Secondary :
- Drugs : Penicillamine, captopril, gold, NSAIDs
- Malignancies : Lung, colon, melanoma
- SLE
- Infections : Chronic hepatitis B & C, syphilis
- Other autoimmune disorders : Thyroiditis

55. Light microscopy :
• Thickening of the glomerular capillary wall
• PAS & Silver stains – GBM spikes are seen projecting into
the urinary space
H&E
PAMS

56. Immunofluorescent microscopy
• Granular global subepithelial
deposits that stain strongest for
IgG
• Less intense for C3

57. Electron microscopy
Subepithelial electron dense
deposits

58. C1q Nephropathy
A controversial entity that is defined by its distinct
immunopathological features
Light microscopy :
• FSGS or
• Normal-appearing glomeruli
• Mild mesangial hypercellularity

59. Electron microscopy :
Mesangial electron dense deposits
Immunofluorescent microscopy :
• Dominant or co-dominant
mesangial positivity for C1q
• Co-staining for IgG, IgM, IgA,
C3

60. Glomerular diseases associated with
Nephritic Syndrome and/or Rapidly
Progressive Glomerulonephritis
Acute Post-infectious Glomerulonephritis
Membranoproliferative Glomerulonephritis
Dense Deposit Disease
Idiopathic Nodular Glomerulosclerosis
Crescentic Glomerulonephritis

61. Acute Post-infectious Glomerulonephritis
(Post-streptococcal, Proliferative)
• Prototypical glomerular disease of immune complex etiology
• Appears 1-4 weeks after a streptococcal infection of the pharynx
or skin
• Usually occurs in children and young adults, although no age is
immune to the occurrence of the disease
• Males > Females

62. H&E, 200x
• Enlarged, hypercellular glomeruli
• Interstitial edema & inflammation
H&E, 400x
Methenamine silver, 400x

63. Coarse, granular, “lumpy-bumpy”
staining of glomerular capillary
loops with IgG & C3
Electron dense sub-epithelial
“hump”

64. Membranoproliferative Glomerulonephritis [MPGN]
(Mesangiocapillary Glomerulonephritis)
Characterised by :
• Thickening of glomerular capillary walls  Membrano
• Hypercellularity in the glomerular tufts  Proliferative
Divided into 2 groups :
• Type I – Subendothelial MPGN
• Type II – Dense deposit disease

65. Light microscopy :
• Glomeruli – Large, Hypercellular
• GBM – “Double-contour” or “tram-track appearance”
• Crescents are present in many cases
Due to duplication of basement
membrane (splitting) : New basement
membrane synthesis in response to
subendothelial deposits of immune
complexes
Methenamine silver, 400x
H&E, 400x
Trichrome, 400x

66. MPGN I
• Granular to band like-C3 in
capillary wall
• Also stain for IgG, C1q,C4
MPGN II
• Glomerular capillary walls
– Band-like staining
• Mesangium – Granular
staining

67. MPGN I MPGN II

68. Idiopathic Nodular Glomerulosclerosis
• Exaggerated mesangial sclerosis
• Glomerular lobularity
This may be idiopathic or seen in cases of :
 MPGN
 Diabetic glomerulosclerosis
 Amyloidosis
 Chronic thrombotic microangiopathies

69. H&E, x400

70. Crescentic Glomerulonephritis
(Rapidly Progressive Glomerulonephritis)
• Rapid and progressive loss of renal function
• Associated with severe oliguria and signs of nephritic
syndrome
• If untreated, death from renal failure occurs within weeks to
months

71. • Characterised by the presence of crescents
• While an occasional crescent may be seen in other
glomerulonephritides, presence in more than 50% of the
glomeruli defines crescentic glomerulonephritis
Produced predominantly by :
• Proliferation of parietal epithelial cells
• Infiltration of monocytes and macrophages

72. Damage to glomerular capillary endothelium and GBM
mediated by anti-GBM antibodies, immune complexes
and/or ANCA
Allow fibrin and other plasma proteins to enter
Bowman’s space and stimulate proliferation of visceral
and parietal epithelial cells
Over time, the cellular crescents either resolve
completely or develop into fibrous crescents

73. On the basis of immunological findings, it is classified into
three groups :

74. PAS
Methenamine silver, 400x

75. Type I
Intense linear staining
along the glomerular
capillary walls for IgG,
with GBM breaks
Type II
Intense granular staining
along the capillary walls
and in mesangium for
IgG

76. Type I
• Disruption of GBM
• No immune-type electron
dense deposits
Type II
Numerous subendothelial,
subepithelial, mesangial
electron-dense deposits

77. Glomerular diseases associated primarily
with asymptomatic or gross hematuria
 IgA Nephropathy
 Henoch-Schonlein Purpura
 Alport Syndrome (Hereditary nephritis)
 Thin basement membrane nephropathy

78. IgA Nephropathy
(Berger’s disease)
 Characterised by:
• Prominent IgA deposits in the mesangial regions
• Recurrent hematuria
 Most common type of glomerulonephritis worldwide
 Commonly seen in older children and young adults
 The disease can be suspected by light microscopic examination, but
the diagnosis is made only by the detection of glomerular IgA
deposition

79. Light microscopy :
Glomeruli may be :
• Normal
• Mesangioproliferative Glomerulonephritis
• Focal proliferative Glomerulonephritis
• Crescentic Glomerulonephritis
Mesangial proliferation and
matrix increase

80. Deposition of IgA in
mesangial regions
Granular immune-type
dense deposits in the
mesangium

81. Henoch-Schonlein Purpura
This childhood syndrome consists of :
• Purpuric skin lesions
• Abdominal pain & intestinal bleeding
• Arthralgia
• Renal abnormalities
• Gross or microscopic
hematuria
• Nephritic syndrome
• Nephrotic syndrome

82. Light microscopy :
• Many overlapping features with IgA Nephropathy
• Mild focal to diffuse mesangial proliferation
• Endocapillary proliferation to crescentic glomerulonephritis

83. PAS, 400x
Glomerulus from a case of mesangioproliferative HSP
nephritis
PAS, 400x
Extra and endocapillary proliferation in pediatric HSP
nephritis

84. Mesangial deposition of
IgA
Granular ‘immune-type’
dense deposits restricted
to mesangium

85. Alport’s Syndrome
(Hereditary Nephritis)
Clinically manifests by :
• Hematuria, with progression to chronic renal failure
• Nerve deafness
• Various ocular disorders
 X-linked recessive
 Due to mutations in one of the genes coding for subunits of
collagen IV molecule

86. Early stages
Ill defined or nil Late stages
Segmental to global
glomerulosclerosis

87. Immunofluorescence
No significance
Electron microscopy
“Basket-weave” pattern

88. Thin Basement Membrane Disease
• Benign familial / Familial asymptomatic hematuria
• Chronic hematuria : - Macroscopic or microscopic
- Intermittent or continuous

89. Light Microscopy
Unremarkable
Immunofluorescence Microscopy
• Standard IF is negative
• Special IF studies for type IV
collagen molecules may identify
thin basement membrane
Electron Microscopy
• Diffuse GBM thinning
• 150 – 225 nm ( Normal : 300 –
400 nm)
Normal

90. Diabetic Nephropathy

91. It is a clinical syndrome characterised by:
• Persistent albuminuria ( >300mg/24hr)
• A steady decline in Glomerular Filtration Rate (GFR)
• Elevated blood pressure

92. Key morphological findings in Diabetic Nephropathy
Diabetic glomeruloscerosis
- Thickening of the basement membranes
- Mesangial matrix accumulation
- Mesangial nodules
- Capsular drop
- Fibrin cap
 Tubular atrophy & interstitial fibrosis
 Afferent & efferent arteriolar hyalinosis
 Arteriosclerosis

93. Masson’s Trichrome, x400
Glomerulomegaly represents the earliest diabetic change detectable by
light microscopy

94. Diffuse form :
Increase in mesangial matrix and uniform thickening of
glomerular capillary walls
PAS, x200
Jone’s methenamine silver
Masson’s Trichrome

95. Capillary walls continue to thicken
Mesangial volume continues to increase
Development of mesangial nodules
Kimmelsteil-Wilson type
Nodular form

96. H&E, x400
Jones’ methenamine silver, x400
Kimmelsteil-Wilson type nodules

97. Fibrin cap Capsular drop

98. Interstitial fibrosis, tubular atrophy, global
glomerulosclerosis in advanced diabetic nephropathy

99. Linear staining along the
tubular & glomerular capillary
basement membranes with
albumin
Severe widening of the
mesangium due to matrix
accumulation

100. Amyloidosis
• Represents systemic deposition of structurally altered light
and/or heavy chain & deposition of other proteins that form
beta-pleated sheets
• All types of amyloidosis share the same light and
ultrastructural features and cannot be differentiated on the
basis of morphological findings
• Proteinuria with or without nephrotic syndrome is the most
common clinical finding

101. Characteristic finding is the presence of amorphous,
eosinophilic material in the glomeruli, interstitium proper and
vascular walls
AL-amyloidosis. H&E,x500
Nodular pattern
AL-amyloidosis. H&E,x500
Diffuse pattern

102. H&E, x350
Amyloid deposition in the interstitium

103. Congo Red
Thioflavin T

104. Electron microscopy

105. Lupus Nephritis
• Systemic Lupus Erythematosus (SLE) is an autoimmune disease of
unknown etiology characterised by inflammation of multiple organ
systems including joints, skin, serosal membranes, CNS , kidney
• This should always be kept in mind as a possible diagnosis in any
young woman with nephrotic syndrome
• Lupus nephritis can give almost any glomerular abnormality and
almost any combination of abnormalities
• Renal disease without immune deposits in SLE patients is termed
as NON LUPUS NEPHRITIS

106. International Society of Nephrology/Renal Pathology
Society 2003 Classification of Lupus Nephritis (LN)
Minimal Mesangial LN
LM – Normal glomeruli
IF – Mesangial immune
deposits
Class I

107. PAS, x400

108. Mesangial Proliferative LN
LM – Mesangial hypercellularity or
mesangial matrix expansion
IF – Mesangial immune deposits
Class II

109. PAS, x400 Immunofluorescence

110. Focal LN
- Focal is defined here to mean that fewer
than 50% of the glomeruli in a specimen are
affected by lesions
- Usually segmental, but occasionally global,
and vasculitic type, active or healed
- Segmental areas of subendothelial immune
deposits, may have mesangial alteration even
affecting all glomeruli
Class III

111. H&E, x400 Immunofluorescence

113. Diffuse Lupus Nephritis
- Segmental or global endo/extra
capillary GN involving >50% of all
glomeruli in a specimen
- Diffuse subendothelial immune
deposits
Class IV

114. JMS, x200 H&E, x500

115. Intense global staining for IgG
Large subendothelial electron-dense
deposits together with numerous
mesangial deposits

116. Membranous LN
- Global or segmental
subepithelial immune deposits on
LM, IF, EM
- Mesangial alterations +/-
Class V

117. H&E, x400 Immunofluorescence

118. Advanced Sclerosing LN
>90% glomeruli are globally
sclerosed without any residual
activity
Class VI

119. PAS, x200

120. TUBULOINTERSTITIAL
DISEASES

121. • Tubular and interstitial diseases are considered together since
injury to one of these compartments almost invariably leads to
injury of the other
They can be :
• Primary lesions of the tubulointerstitial compartment or
• Secondary to glomerular or vascular disease of the kidney

122. Acute Tubular Injury/Necrosis (ATN)
• It may be defined simply as acute deterioration of renal
function associated with tubular epithelial cell injury
• Common causes include :
- Ischemia
- Nephrotoxins

123. Normal kidney ATN

124. PAS, 400x
Single cell epithelial necrosis, apoptosis, segmental
coagulative necrosis of tubules
PAS, x400
Injured epithelial cells lose adhesion for the tubular
basement membrane & accumulate in the lumen as
PAS, x200
Interstitium may have mild edema with sparse
mononuclear & neutrophilic infiltrates

125. Tubulitis
• Lymphocytes or other
inflammatory cells on
epithelial side of tubular
basement membrane
infiltrating the tubular
epithelium
• Marker of active
tubulointerstitial
inflammation

126. Tubular atrophy
• Tubules are non-functioning and no longer capable of
regenerating and resuming function
• Accompanied by thickening of basement membrane
3 types of atrophied tubules :
• Classic atrophic tubules : Thick wrinkled tubular BM,
simplified cuboidal epithelium
• Endocrine tubules : Narrow/no tubular lumen, clear
epithelial cells, thin/absent BM
• Thyroidised tubules : Round tubules, simplified epithelium,
uniform intratubular casts that mimic thyroid

127. Thickened basement
membrane
Thyroidisation

128. Light Chain Cast Nephropathy
(Myeloma Kidney)
H&E, x500
Prominent casts in the distal nephrons
H&E, x500
Reactive tubular epithelial cells admixed with
multinucleated giant cells

129. Pathological diagnosis of Interstitial diseases :
Interstitial expansion by edema :
• ATN
• Renal vein Thrombosis
• Nephrotic syndrome (MCD)
• Acute Glomerulonephritis
• Thrombotic microangiopathy
Interstitial expansion by eosinophilic material :
• Collagen-fibrosis
• Sickle cell disease
• Radiation nephritis
• Amyloidosis

130. Interstitial expansion by leukocytes :
• Polymorphs (APSGN, drug induced, sepsis)
• Lymphoplasmacytic (Chronic nephritis, vasculitis, rejection)
• Eosinophilis (Vasculitis, drug induced, lupus)
• Epitheloid (TB, Sarcoidosis, drug induced, Malakoplakia)
Expansion by foam cells :
• Alport’s syndrome
• Membranous GN
Interstitial haemorrhage :
• Acute rejection
• Malignant HTN
• Vasculitis

131. Interstitial expansion by neoplastic cells :
• Lymphoma/Leukemia
• Primary renal cell carcinoma
• Metastasis
Crystals & mineral deposits :
• Nephrocalcinosis  Calcium carbonate
• Acute renal failure  Calcium oxalate
• Gout  Uric acid
• Glomerular disease with Nephrotic syndrome  Cholesterol

132. VASCULAR LESIONS

133. • Renal vessels are susceptible to many damages
• Many immune complexes reach the kidney through blood
circulation and are filtered in glomeruli
• Receiving about 20% of the cardiac output, the kidneys are
constantly exposed to the damaging elements which circulate
in blood

134. The main injuries of vascular elements are :
Vasculitis
• Systemic injury
• Local injury - due to toxins, infection, inflammation
Deposition of materials
• Amyloidosis
• Immune complexes
• Arteriosclerosis

135. Hypertension induced injuries
• Hypertrophy of media
• Intimal thickening
• Fibrinoid necrosis
• Thrombotic microangiopathy
• Fibrointimal hyperplasia
Endothelitis
• Drug induced
• Toxins

136. Benign Hypertension
• Arteriosclerosis is attributed to benign hypertension but also
increases with age & is seen in patients who have never been
known to have elevated blood pressure
• Prevailing scientific opinion regards renal arteriosclerosis as being
a hypertrophic response to elevated pressure
• Another view suggests that it represents premature aging of the
arteries and may be the cause of hypertension

137. Two types of pathology of small arteries & arterioles
• Hyaline arteriosclerosis
• Intimal fibrosis

138. Hyaline arteriosclerosis
• Affects afferent arterioles
• More severely involved Interlobular arteries

139. Intimal fibrosis
• Collagenous connective tissue that thickens the intima &
narrows the lumen of the affected vessels
Mild Intimal fibrosisMarked Intimal fibrosis

140. Accelerated and Malignant Hypertension
Characterised by two renal vascular lesions:
• Hyperplastic arteriosclerosis
• Fibrinoid necrosis

141. Hyperplastic arteriosclerosis
• Most prominent in : - Afferent arterioles
- Interlobular arteries
• Also seen in : Thrombotic microangiopathies
Hyperplastic arteriolosclerosis
“onion-skinning”

142. Fibrinoid necrosis :
• Seen in : - Afferent arterioles
- Glomeruli
• Often involves vascular pole of the glomerulus in continuity
with fibrinoid arteriolar necrosis

143. BIOPSY OF A RENAL
ALLOGRAFT

144. • Indication :
Impaired excretory function  Graft dysfunction
• Two common problems:
• Active, acute rejection that may respond to treatment OR
• Chronic damage that will not respond to treatment
• The diagnoses related to acute rejection :
• Antibody-mediated rejection
• Acute cellular rejection
• Acute vascular rejection
• Severe acute vascular rejection

145. Other reasons for biopsy of an allograft :
• To evaluate drug induced nephrotoxicity
• After surgical removal, to see if kidney is suitable to be
transplanted
• Immediately after the kidney has been grafted, either as a wedge of
the capsular surface or as a needle biopsy  Implantation
biopsy/Post perfusion biopsy/30 min biopsy
• At set intervals after transplantation, irrespective of renal function
Protocol biopsy specimen

146. Technical handling of renal allograft biopsy specimens
The Banff group suggested in 1997 that an adequate
specimen had :
• At least ten glomeruli and at least two arteries
• The minimum requirement was seven glomeruli and one
artery
• With at least two cores of cortex or two areas of cortex
on the same core
• Studied with multiple sequential sections, 3–4 µm thick
• On seven slides, 3 stained with H&E, 3 with either PAS
or periodic acid methenamine silver and 1 with a
connective tissue stain

147. Antibody mediated rejection
• Hyperacute rejection is the most dramatic type of antibody-
mediated rejection, which may be seen in a form that can be
called delayed hyperacute or accelerated acute rejection
• May be due to antibodies in the recipient against HLA or
non-HLA antigens in the graft
• Occurs : First few weeks after transplantation

148. Cortex in a biopsy specimen of a kidney taken 4
days after transplantation

149. • A marker that there has been a reaction between antibodies
and endothelium is C4d
An inactivated form of the
complement component C4
Immunoperoxidase stain

150. Conventional acute rejection
Acute Cellular
rejection
Acute Vascular
rejection
• Occurs :Within the first few weeks, but can occur at any time
after transplantation, for instance if there is a change in dose or
type of immunosuppressive drugs
• About 1/4th of transplant recipients have at least one episode of
acute rejection

151. Acute cellular rejection
10x40x

152. Scheme suggested by the Banff group in 1997 for the threshold
for diagnosis of clinically significant acute cellular rejection:
• At least 25% of the cortical area has an inflammatory
infiltrate, by guess work
• There are at least four lymphocytes within a tubule in more
than one area

153. Acute vascular rejection
• Widening of the space between the
endothelium and the underlying
tissues in arteries of any size, with
infiltration of lymphocytes into this
space
• Easier diagnosis to make than acute
cellular rejection : because any
definite features of acute vascular
rejection are significant, no matter
how small or scarce
• Not even the full circumference of an
artery has to be affected
Cortex in a needle biopsy
specimen of kidney taken 13 days
after transplantation

154. Changes in the intima of venules & veins are not considered
significant !!!

155. Chronic rejection
• Occurs : Years after
transplantation
• It is a condition in which arteries
develop concentric intimal
thickening, without an
inflammatory infiltrate in the
intima
• Tubules show atrophy as a result
of ischemia
• Glomeruli may be shrunken, also
from ischemia
Concentric intimal thickening

156. INVESTIGATION OF A RENAL
MASS

157. • Biopsy is usually avoided
• The findings are unlikely to change management and there is
a risk of dissemination of cancer along the biopsy track
• Biopsy may be considered if there is disseminated neoplasia
to see whether there is a primary malignant neoplasm in the
kidney, or whether the renal mass is a metastasis

158. GENERATION OF RENAL BIOPSY
REPORT
Light microscopy
 The presence & relative proportion of the renal cortex, medulla,
renal capsule, pelvic urothelium & others (skeletal muscle, liver)
 Number of glomeruli present & the percentage of globally
sclerosed glomeruli if any :
<40 yr – 10%
>40 yr – More & variable
 Description of diagnostic morphologic lesions/changes/patterns
in each of the four compartments

159. Glomerular changes
• Focal/diffuse
• Segmental/global
• % of glomeruli involved
• Glomerular size
• Glomerular cellularity
• Glomerular capillary potency
• GBM changes
• Mesangial widening
• Mesangial cellularity
Tubules, interstitium ,vessels
• Focal/diffuse
• Estimate of severity
Negative findings
• Absence of necrosis
• Absence of amyloid

160. Immunofluorescence
• Number of glomeruli in frozen section
• Description of positive & negative results with number of
glomeruli, location of deposits, their relative intensity of
staining
• Evaluation of all 4 compartments for immune deposits

161. Electron microscopy
• Total number of glomeruli
• Description of glomerular abnormalities/changes
• Immune deposits – present/absent
• If present, location, number, appearance, size should be stated
• Description of degree of foot process effacement
• Tubular epithelial cells, TBM, interstitium & vessels should also
be examined

162. DIAGNOSIS
• Pattern of glomerular disease
• If possible, depending on clinical information available,
more specific diagnosis should be offered
• If no diagnosis on LM, IF, EM, then only a descriptive
morphologic pattern should be given with a comment

163. Comment :
• Clinicopathological correlation
• List of differential diagnoses if necessary
• Pertinent histological prognostic indicators
• Activity/chronicity indices of Lupus Nephritis

164. TAKE HOME MESSAGE
• Kidney biopsy is an indispensable tool for
current practice of evidence-based medicine
• The clinicopathological correlation is a great
challenge for both pathologists and
nephrologists
• LM, IF, and EM should be done routinely in all
biopsies
• Kidney biopsy, appropriately processed and
interpreted, will yield the correct clinicopathological
diagnosis, leading to the appropriate therapeutic
strategy while, at the same time, providing key
prognostic information

165. References
1. Zhou XJ, Laszik Z, Nadasdy T, D`Agati VD, Silva FG. Diagnostic Renal
Pathology.1st ed. New York:Cambridge University Press;2009
2. Howie AJ. Handbook of Renal Biopsy Pathology. 2nd ed. London:
Springer;2008
3. Jenis EH, Lowenthal DT. Kidney Biopsy Interpretation. Philadelphia :
F.A.Davis Company
4. Kumar V, Abbas AK, Aster JC. The Kidney. Elsevier (ed). Robbins & Cotran
Pathologic Basis of Disease. 9th ed. Gurgaon : Reed Publisher;2014 . P.897-
957
5. Agarwal SK, Sethi S, Dinda AK. Basics of Kidney biopsy : A Nephrologist’s
perspective. Indian J Nephrol.2013;23 :243-252

166. 6. Fogo AB, Cohen AH, Jennette JC, Bruijn JA, Colvin RB. Fundamentals of renal
pathology. London: Springer;2006.Weening JJ, D’Agati VD, Schwartz MM, et al.
The classification of glomerulonephritis in systemic lupus erythematosus revisited.
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7.Amoueian S, Attaranzadeh A. Topics in Renal biopsy and Pathology. Europe:
Intech Publishers ;2012