Kein Folientitel

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All about chronic? M.J. Mihatsch, V. Nickeleit
and F. Gudat
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Rejection in the kidney
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Principles of Solid Organ Tx Rejection (I)
Organ
Parenchyma
Stroma or Interstitial tissue
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Principles of Solid Organ Tx Rejection (I)
Organ
Interstitial R. (cellular)
Parenchyma
Stroma or Interstitial tissue
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Principles of Solid Organ Tx Rejection (I)
Type of Rejection (R.)
Immune Reaction (IR)
Prevalence
Interstitial R. (cellular)
T-cell mediated IR
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Principles of Solid Organ Tx Rejection (I)
Organ
Parenchyma
Stroma or Interstitial tissue
Vascular R.
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Principles of Solid Organ Tx Rejection (I)
Type of Rejection (R.)
Immune Reaction (IR)
Prevalence
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Principles of Solid Organ Tx Rejection (I)
Type of Rejection (R.)
Immune Reaction (IR)
Prevalence
Interstitial R. (cellular)
T-cell mediated IR
66
T-cell mediated IR Humoral IR, C4d pos.
Preformed AB
lt1
Interstitial R. (cellular)
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Principles of Solid Organ Tx Rejection (II)
Restitutio ad integrum
Damage (Scar)
Fibrosis/Scar Parenchymal- interstitial space
remnant cellular infiltrates
Complete resolution (no remnant damage visible)
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Principles of Solid Organ Tx Rejection (I)
Restitutio ad integrum
Damage (Scar)
Fibrosis/Scar Parenchymal- interstitial space
remnant cellular infiltrates
Complete resolution (no remnant damage visible)
Intimal Fibrosis remnant cellular infiltrates
No functional/morphological sequelae in
parenchyma and interstitial tissue
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What is chronic from the morphological point of
view?
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Schematic Development of Chronic Rejection
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Media
Media
1.Biopsy 2.Biopsy
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QuestionWhat is chronic from the
morphological point of view?AnswerPresence of
collagen in wound healing, organization tissue
and inflammation.Collagen production 3-6 days
after the onset
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What is Chronic Rejection ?
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Disease Course Depending upon the Number and
Severity of Rejection Episodes
Rejection episodes
time
time
"chronic" rejection scar
gt200 µmol/l
Renal mass ? S-creatinine ?
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Disease Course Depending upon the Number and
Severity of Rejection Episodes
Rejection episodes
time
"chronic" rejection scar
"chronic" rejection scar
gt200 µmol/l
Renal mass ? S-creatinine ?
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Disease Course Depending upon the Number and
Severity of Rejection Episodes
Rejection episodes
time
"chronic" rejection scar
"Chronic" progressive rejection
"chronic" rejection scar
gt200 µmol/l
Overload nephropathy
Renal mass ? S-creatinine ?
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OuestionWhat is Chronic Rejection ?Answer
Repeat acute rejection episodes!!!
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OuestionWhat is Chronic Rejection ?Answer
Repeat acute rejection episodes!But
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Principles of Solid Organ Tx Rejection (I)
Restitutio ad integrum
Damage (Scar)
Fibrosis/Scar Parenchymal- interstitial space
remnant cellular infiltrates
Complete resolution (no remnant damage visible)
Intimal Fibrosis remnant cellular infiltrates
No functional/morphological sequelae in
parenchyma and interstitial tissue
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OuestionWhat is Chronic Rejection ?Answer
Repeat acute rejection episodes!ButRejecti
on may be superimposed by overload damage
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OuestionWhich compartments allow the dignosis
of chronic rejection ?
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Morphological Types ofChronic Rejection

• Vascular
• TV with intimal fibrosis
• Glomerular
• Transplant glomerulopathy
• (Tubulo-interstitial?)

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Glomerular RejectionGlomerulitis
Glomerulopathy
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Immunohistochemical staining of many monocytes
(OKM1, Kryo-section)
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Glomerular loop filled with mononuclear cells,
one of them in mitosis.
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Tx-glomerulopathy with FSGS (overload glom.)
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TP-Pathy
TP-gitis
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Vascular Rejection

• TV with massive intravascular coagulation
• Necrotizing TV
• Infiltrative / proliferative TV
• Sclerosing TV
• Mixed form / relapsing TV

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Media
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Lumen
Media
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L
Media
Media
L
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CD8 Suppressor/Killer-Lymphocytes
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Media
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Media
L
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Media
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Dark brown collagen type III
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VR-Scler.TV
VR-Prolif.TV
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OuestionWhich comartments allow the diagnosis
of chronic rejection ?Answer Arteries TV
with intimal fibrosisGlomeruli Tx-
glomerulopathy
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Ouestion What is the difference between
chronicvascular rejection and other chronic
vascular lesions?
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Factors in the Development of Sclerosing
TV(Graft Arteriosclerosis)
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2. Biopsy
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Media
NO! elastosis
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Severe degenerative elastosis
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Morphological Features indicative of Sclerosing
Tpl-Vasculopathy

• Concentric intimal fibrosis
• Excentric intimal fibrosis covering scars of the
  media
• Excentric intimal fibrosis at branch points of
  arteries
• Fragmentation of elastic lamellae
• Foam cells
• Focal mononuclear infiltrates
• Irregular proliferation of myofibroblasts
  (crowding)
• Polymorphism, hyperchromasia, enlargement of
  endothelial nuclei
• Neo-media formation
• IgM, complement C3, eventually fibrin deposits
• Associated lesions tpl-glomerulopathy,
  interstitial cellular rejection
• Absence of elastosis

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Ouestion What is the difference between
chronicvascular rejection and other chronic
vascular lesions? Answer Many morphological
features! -but for how long do they perist?
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Ouestion What is the difference between
chronicrejection and chronic Tx-nephropathy
and is it clinically relevant?
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To Banff or not to Banff,that is the question ...

• Definition of chronic allograft nephropathy
• Mild to severe chronic ischemic or
• transplant glomerulopathy and/or
• mild to severe interstitial fibrosis and
• tubular atrophy

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Chronic TransplantNephropathy
Rejection
Recurrent disease
CSA Tox
Hypertension Hyperlipidemia
Overload nephropathy
Age
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Definition of Chronic RenalTransplant
Nephropathy

• Interstitial fibrosis, striped pattern
• Arteriolopathy, unspecific
• Glomerulopathy, unspecific
• Interstitial inflammation,
• no tubulitis, HLA-DR negative

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Differential Diagnosis of Interstitial Fibrosis

• 1. Scars
• Ae Destruction of renal tissue
• Ex Infarcts, pyelonephritis, previous biopsy
• 2. Subcapsular band-like fibrosis
• Ae Ischemic damage of the outer cortex due to
  interruption of capsular blood flow
• 3. Diffuse cortical interstitial fibrosis without
  tubular atrophy
• Ae Persistent interstitial edema
• Ex Obstruction of urinary tract, ATN (long
  lasting)
• 4. Focal / diffuse cortical interstitial fibrosis
  with tubular atrophy
• Ae Hypoxic damage, immune reactions
• Ex Rejection, CSA-arteriolopathy,
  glomerulonephritis etc.

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Prognostic Impact of DifferentMorphological
Patterns onOutcome (3 mths after biopsy)
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Prognostic Impact of Chronic Morphological
Lesions and S-creatinine at the Time of Biopsy on
Outcome (3 mths after biopsy)
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Ouestion What is the difference between
chronicrejection and chronic
Tx-nephropathy?AnswerRejection is an
immunologically mediated damage or the result
thereof.Chronic Tx-nephropathy is an unspecified
renal lesion.
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Ouestion Is it clinically relevant to
differentiate between chronicrejection and
chronic Tx-nephropathy ?AnswerYes- may have
different clinical implications
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OuestionWhat is Chronic Rejection for the
clinician?Answer Unexplained deterioration of
renal function 6 months after Tx.
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Chronic rejection S-creatinine increasegt 6
mths after transplantation

• Rejection 50
• Glomerulonephritis, CSA - toxicity etc. 25
• Unspecific renal damage 25
• Chronic renal transplant
• Nephropathy / dysfunction

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OuestionWhat is Chronic Rejection for the
clinician?Answer Unexplained deterioration of
renal function 6 months after Tx.From the
point of view of a pathologist mixed bag of
different lesions. In only 50 morphological
rejection is present.
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A better definition of chronic rejectionfrom
the clinical point of view
Chronic
Acute
S-Crea
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OuestionIs it worth while to retain the term
Chronic?Answer NoThe term Chronic is the
permanent source of misunderstanding!
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• Acute
• Coming sharply to a climax, occurring rapidly
• In terms of time minutes - days
• Chronic
• Long lasting
• In terms of time weeks - years
• G. Majno and I. Joris Cells, tissues and
  diseases 1996

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Terminology

• Clinical
• acute
• chronic

• Morphological
• IVC / Necrosis/
• cellular infiltration
• cellular proliferation
• Sclerosis / fibrosis