Acute Graft Rejection of Kidney Transplantation

1. Slide Presentation
HISTOLOGY
Sansar Babu Tiwari, MBBS, PGY II
Department of Pathology
TUTH
15th February 2021
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2. 1. History of transplant
2. Basic overview of immune responses in graft
rejection
3. Normal Anatomy of kidney
4. Banff Classification of Renal Allograft Rejection
5. Case details
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3. – Modern era of transplantation began in the 1950s
– First successful kidney transplant was done in
1954 in Brigham Hospital in Boston between
identical twins survived for 8 years and recurrence
(major risk factor in twin recipients)
– 1945 (Cadaver, septicemia), 1952 (Mother to son,
single kidney, accident), 1954 (twin without
immunosuppression)
– Medawar found that allograft rejection is due to
the immune response rather than non-specific
inflammatory response.
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4. – There is no need to take account of rhesus antigen
compatibility in organ transplantation.
– Permissible transplants are from:
• Group O donor to O, A, B or AB recipient
• Group A donor to group A or AB recipient
• Group B donor to group B or AB recipient
• Group AB donor to group AB recipient
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Rubin Zhang CJASN 2018;13:182-192

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33. Perplexing challenge to the pathologists.
Why?
• There is little time for consultation
• Several disease can occur simultaneously
• Wide range of potent therapy is possible
whose selection depends on the accuracy
of the diagnosis
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37. Calcineurin inhibitors are the mainstay of
most standard protocols. (Cyclosporin,
Tacrolimus)
+
Corticosteroids
+
Mycophenolate mofetil or Azathiprine
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38. Short course of high dose steroids (oral)
for 2 – 3 days
If necessary rescue by ATG (anti-
thymocyte globulin)
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39. Renal biopsy: Gold standard to determine
the cause of graft dysfunction.
– 30% of recipients early after transplant.
– 2 to 4 % per year after the first year.
Biopsy findings change the clinical
diagnosis in an average of 36% of patients
and therapy in 59 %.
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40. The sensitivity of single core is 90%.
The predicted sensitivity of 2 cores is 99%.
Ultrasound guided biopsy.
No death among 5026 patients. (safe)
16-gauge better than 18-gauge (No
complications)
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42. 5 sections at 3 levels (3 slides)
5 sections for Trichome (1 slide)
5 sections for PAS (1 slide)
Total (5 slides)
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43. Each section is carefully examined for
a. Nature and degree of interstitial
cellular infiltrate
b. Arterial and arteriolar lesions
c. Tubular injury, inflammation
(tubulitis), viral inclusion bodies
d. Glomerular lesions
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44. At least 10 non-sclerotic glomeruli
2 arteries
A normal medulla does not rule out
rejection (low sensitivity)
C4d staining can be done in tubules if
sparse tissue
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46. Introduced in Banff, Canada in 1993
Had undergone number of significant
modifications
The most important of these were the
incorporation of NIH Cooperative Clinical Trials
in Transplant in 1999 which separated the
category of endarteritis and addition of AMR in
2003.
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48. Areas that must not be considered for Banff “I”
• Fibrotic areas
• Immediate subcapsular cortex
• Adventitia around large veins and lymphatics
Asterisk (*) shall be placed if there are more
than 5% to 10% eosinophils, neutrophils or
plasma cells.
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51. The presence of mononuclear infiltrate in the
basolateral aspect of the renal tubule epithelium.
(Reversed from 2015 leukocyte to 1997
mononuclear cells)
The most severely affected tubule determines the
score.
Severely atrophic tubules (<25% of unaffected
kidney) excluded.
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55. Arteries are defined as having 2 layers of
smooth muscles in the media.
Intimal arteritis (endothelialitis or endarteritis)
is defined by the presence of inflammatory
cells, mainly lymphocytes and monocytes in the
subendothelial space of one or more arteries.
Seen in both Acute TCMR and Active AMR.
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56. Similar lesions in arterioles are only coded as an
asterisk behind the Banff lesion score “ah” and
are disregarded for “v”.
Infiltrates buried deep into the intima are not
considered for “v” but have been recognized as
Chronic Active TCMR since 2005 and graded in
the 2017 update as Grade II.
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57. Asterisk (*) in “v” is attached when there is
presence of tubulointerstitial hemorrhage
and/or infarct.
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59. Glomerulitis is a form of microvascular
inflammation (MVI) and is a feature of activity
and antibody interaction with tissues in AMR.
Defined as “complete or partial occlusion of 1
or more glomerular capillary by leukocyte
infiltration and endothelial cell enlargement”.
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61. Determines the degree of inflammation within
the peritubular capillaries.
Together with glomerulitis, ptc constitutes MVI
as a feature of Active AMR or Chronic active
AMR.
Peritubular capillaritis can be observed with
pure acute TCMR or Borderline as well.
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62. PTC are by definition found in the cortex.
The number of luminal inflammatory cells
includes PMN and mononuclear leukocytes.
Asterisk (*) is used to indicate only
mononuclear cells in the absence of
neutrophils.
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63. The extent of ptc inflammation should be
documented either as
Focal (10-50% of cortical area)
Diffuse (>50% of cortical area)
But this does not contribute to the score.
Inflammatory cells within veins and medullary
capillaries should not be scored.
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73. Not used to reach a diagnostic category and is
purely descriptive
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74. PAS positive arteriolar hyaline thickening.
Asterisk (*) is added when arteriolitis is present.
Not used to reach a diagnostic category and is
purely descriptive
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76. Not used to reach a diagnostic category and is
purely descriptive
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77. All of the cortical parenchyma including areas of
interstitial fibrosis and tubular atrophy (IFTA),
subcapsular cortex and perivascular cortex including
nodular infiltrates are considered for “ti” scoring.
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Category 3: Suspicious (Borderline) for Acute TCMR
Foci of Banff t > 0 AND Banff i ≤ 1
OR
Foci of Banff t1 AND Banff i ≥ 2

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90. • 48 year old male
• Transplantation done 1 week back
• Creatinine 3.9 mg/dl
• 1 H & E stained slide
• 1 PAS stained slide
• 1 Trichome stained slide
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111. Sections show renal parenchyma with glomeruli, tubules
and interstitium along with few arterioles.
There are 7 glomeruli, none of them show features of
gomerulitis, double contour glomerulus and mesangial
matrix proliferation. (g0, cg0, mm0)
The proximal and distal tubules are focally infiltrated by
the mononuclear cell infiltrate which constitutes less
than 4 cells per 10 tubular epithelium even in severely
affected areas (t1). Tubular atrophy are not seen (ct0).
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112. Interstitium shows few foci of edematous areas as
well as nodular infiltration of predominantly
mononuclear cells in less than 10% of unscarred
cortical parenchyma (i0).
Peritubular capillaries show at least one leukocytes
in most of them with upto 4 in severely affected
one (ptc1).
Arteritis, fibrous thickening, arterial hyalinosis or
hyaline arteriolar thickening are not seen in any
form (v0, cv0, ah0, aah0)
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113. Interstitial fibrosis is not seen with Masson's
Trichome stain (ci0, i-IFTA0).
Total inflammation constitutes less than 10% of
the renal parenchyma (ti0).
C4d staining is not available (C4dx).
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114. Tubular vacuolization or nuclear inclusions are
not seen.
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i 0 ptc 1 mm 0
t 1 ci 0 ah 0
g 0 ct 0 aah 0
v 0 cv 0 ti 0
c4d - cg 0 i-IFTA 0

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Category 3: Suspicious (Borderline) for Acute TCMR
Foci of Banff t > 0 AND Banff i ≤ 1
OR
Foci of Banff t1 AND Banff i ≥ 2

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119. Diagnosis:
Suspicious for Acute TCMR (t1, ptc1)
Differential diagnosis:
Active AMR (provided c4d IHC>0 or c4d IF>1 and
DSA positive)
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120. • Thankyou!!!
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