Download changes suggesting chronic rejection Banff 97 Classification of

Renal Pathology Review
Medical Diseases of the Kidney
Karlene Hewan-Lowe, MD
Brody School of Medicine at East Carolina University
Renal Pathology
The Osler Institute Review Course
Amyloidosis
Immunofluorescence Microscopy
• May stain for monoclonal light
chains
Electron Microscopy
• Randomly arranged, rigid,
nonbranching filaments
• 7 – 10 nanometers
Prognosis
• Uniformly poor
• Colchicine limits progression
of AA amyloidosis in Familial
Mediterranean Fever
Renal Pathology
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Fibrillary Glomerulopathy
Clinical Features
• Associated with chronic lymphocytic leukemia, Bcell lymphoma
• Renal insufficiency
• Hematuria
• Hypertension
Pathogenesis
• Monotypical IgG may have role in fibrillogenesis
Renal Pathology
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Fibrillary Glomerulopathy
Light Microscopy
•Mesangial hypercellularity
•Mesangial expansion
Immunofluorescence
Microscopy
•Linear staining staining with
IgG, C3, kappa and lambda
Renal Pathology
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Fibrillary Glomerulopathy
Electron Microscopy
• Randomly distributed
fibrils
• Diameter – 20 to 30 nm
Renal Pathology
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Light Chain Deposition Disease
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Second most common plasma cell related disorder
Nephrotic syndrome or heavy proteinuria
MPGN type pattern of glomerular injury
Monoclonal deposision – kappa light chains
Finely granular, ribbon-like subendothelial deposits in GBM
Myeloma Cast Nephropathy
• Acute renal failure
• Refractile, angular intraluminal casts and multinucleated giant cells
Renal Pathology
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Glomerular Diseases Associated
with the Nephritic Syndrome
• Acute postinfectious glomerulonephritis
• Crescentic (rapidly progressive)
glomerulonephritis
• IgA Nephropathy/Henoch Schonlein purpura
Renal Pathology
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Acute Post Infectious
Glomerulonephritis
Clinical Features
• Beta hemolytic Streptococcus Type 1, 4, 12, 49
• Skin, pharyngitic infections and deep seated
abscesses
• Nephritic Syndrome
• Elevated ASO titre
• Decreased serum complement, C3
Pathogenesis
• Immune complex mediated glomerular injury
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Acute Post Infectious
Glomerulonephritis
Light Microscopy
• Large, hypercellular glomerular tuft
• Neutrophilis infiltrate the glomerular tuft
Immunofluorescence Microscopy
• Lumpy-bumpy, granular mesangial and peripherat
capillary wall deposits for IgG and C3
Electron Microscopy
• Subepithelial humps
• Scattered mesangial and subendothelial deposits
Renal Pathology
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Crescentic (Rapidly Progressive)
Glomerulonephritis
• Precipitous renal failure
50% or greater loss of renal
function within three months
• Crescentic GN is defined as
glomerulonephritis in which
there are >50 % crescents
• A severe morphologic
expression of glomerular injury
• Immunologic mechanisms, fibrin
and inflammatory mediators
have a role in the formation of
crescents
Renal Pathology
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Crescentic (Rapidly Progressive)
Glomerulonephritis
Anti-GBM disease
Immune complex mediated glomerulonephritis
Pauci immune glomerulonephritis
Renal Pathology
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Crescentic (Rapidly Progressive)
Glomerulonephritis
ANCA Related Diseases
• ANCA are serologic markers for pauci immune
crescentic GN
• In the presence of ANCA an associated systemic
vasculitis should be considered
• PR3-ANCA (C-ANCA) – more frequent in Wegener’s
granulomatosis
• PR3-ANCA (C-ANCA) and MPO-ANCA (P-ANCA) occur in
patients with polyarteritis nodosa
• MPO-ANCA (P-ANCA) more frequent in Churg-Strauss,
ANCA-GN (idiopathic crescentic GN)
Renal Pathology
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IgA Nephropathy/Henoch Schonlein
Purpura
Clinical Features
• Most common glomerular disease in the world
• Hematuria
• Nephritic Syndrome
• Variable Proteinuria
• HSP – abdominal pain, joint pain and purpura
Pathogenesis
• Inadequate clearance of an abnormally
glycosylated IgA
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IgA Nephropathy/Henoch Schonlein Purpura
Pathology
• Mesangial proliferation
• IgA in mesangium
• Mesangial and paramesangial
immune complex, electron
dense deposits
Prognosis
• Slow progression to ESRD
• HSP in children – complete
resolution
Renal Pathology
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Thin Basement Membrane Disease
Clinical Features and Pathology
• Asymptomatic hematuria
• No immune complexes by immunofluorescence or
electron microscopy
• Basment membrane < 300 nanometers
• No progression to ESRD
Pathogenesis
• Abnormal gene that controls formation of alpha
chain Type IV
Renal Pathology
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Secondary Diseases
Renal Pathology
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Systemic Lupus Erythematosus
Clinical Features
• African American women, age 20
• Systemic disease
Arthralgia, arthritis, skin rashes, inflammation of
serous surfaces
• Clinical evidence of renal disease is present in 50 to
70% of patients with SLE
• Renal disease is less common in drug related SLE –
chlorpromazine, hydralazine. Methlyldopa,
procainamide
Renal Pathology
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Systemic Lupus Erythematosus
Pathogenesis
• Immune complex – antibody to a variety of nuclear
constituents
• Increased apoptosis in lupus patients induces
excessive autoantibody against nuclear proteins and
nucleic acid sequences
Renal Pathology
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Systemic Lupus Erythematosus
ISN/RPS Classification of Lupus Nephritis
• CClass I
Minimal mesangial lupus nephritis
• CClass II
Mesangial ICD by IF and EM
Mesangial Proliferative lupus nephritis
Mesangial hypercellularity
• CClass III
Mesangial ICD by IF and EM
Focal proliferative lupus nephritis
Focal and segmental glomerular lesions
Focal interstitial inflammation
Mesangial, subepithelial and subendothelial
deposits
Renal Pathology
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Systemic Lupus Erythematosus
ISN/RPS Classification of Lupus Nephritis
• CClass IV
Diffuse proliferative lupus nephritis
Hypercellular glomerular tuft
Membranoproliferative type pattern
“Wire loop” lesions, hyaline thrombi
• CClass V
Membranous lupus nephritis
Mesangial hypercellularity
Refractile, thick glomerular basement membranes
Mesangial deposits
• CClass VI
Chronic sclerosing lupus nephritis
Renal Pathology
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Systemic Lupus Erythematosus
• Renal Symptoms correlate with morphologic
classification
• Class I and II lupus nephritis
Hematuria
Mild proteinuria
• Class II and IV lupus nephritis
Nephritic syndrome
Nephrotic syndrome
Low serum complement
• Class V lupus nephritis
Nephrotic syndrome
Renal Pathology
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Systemic Lupus Erythematosus
• Immunofluorescence
“Full house”
Mesangial deposits – Class I and II
Mesangial and capillary wall deposits – Class II and IV
Capillary wall deposits – Class IV
• Electron Microscopy
Mesangial electron dense deposits are always present
Subendothelial deposits – Class III and IV
Supepithelial deposits – Class V
Tubuloreticular structures in endothelial cells
Renal Pathology
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Thrombotic
Microangiopathy
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HUS
TTP
FK506
Cyclosporine
Systemic lupus
Anti-phospholipid syndrome
Malignant hypertension
Acute phase of scleroderma
Cancer and chemotherapy
Renal transplantation - recurrent
and de-novo
 Bone marrow transplantation
 HIV infection
Renal Pathology
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Hereditary Nephritis
Renal Pathology
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Alport’s Syndrome
• X-linked inheritance in 80% of cases
• Other patterns – autosomal recessive, autosomal
dominant
• Clinical features
Microscopic hematuria
Proteinuria
Early progression to end stage renal failure (males, 30)
Ocular lesions
Sensoneuronal deafness
Renal Pathology
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Alport’s Syndrome
• Light Microscopy
Glomerulosclerosis
Tubular atrophy and interstitial fibrosis
Interstitial foam cells
• Electron Microscopy
Moth eaten glomerular basement membrane
Foci of thickening and thinning
• Pathogenesis
One or more mutations in COL4A5 gene
Long arm of X - chromosome
Renal Pathology
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Other Renal Diseases
Tubulointerstitial Diseases
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Acute tubular necrosis
Acute pyelonephritis
Interstitial nephritis
Cast nephropathy
Myeloma
Myoglobin
• Analgesic nephropathy
Renal Pathology
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Pathology of Renal
Transplants
Renal Pathology
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Pathology of Renal
Transplants
Banff 97
Classification of Renal
allograft Rejection
Updated 2001
Lake Louise, Banff, CA
Renal Pathology
Pathologic Markers of
Antibody/Humoral Rejection
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Neutrophils in
peritubular capillaries
Neutrophils in
glomerular capillaries
Neutrophilic tubulitis
Fibrinoid necrosis of
arteries and capillaries
Fibrin thrombi
Infarction
Acute tubular injury
C4d in peritubulqr
cqpillaries
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Renal Pathology
Pathologic Markers of Cellular
Rejection
Swollen, pale kidney
Tubules - Tubulitis
Interstitium - interstitial infiltrate of
inflammatory cells
Vessels - Endarteritis
Immunofluorescence
Fibrinogen and increased
C3 along the tubular
basement membranes
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Renal Pathology
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Markers of Chronic
Rejection
• Transplant glomerulopathy
• Tubular atrophy and fibrosis
• Vessels
Intimal proliferation
Subintimal foam cells
Vessel in vessel
Renal Pathology
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Banff 97 Classification of Renal allograft Rejection
Updated 2001
1. Normal
Renal Pathology
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Banff 97 Classification of Renal allograft Rejection
Updated 2001
2. Antibody Mediated Rejection
Rejection due, at least in part, to
documented anti-donor antibody
Report as ‘Suspicious for’ if NO anti-donor
antibody
Type (Grade)
I. ATN like, minimal inflammation
C4d+
II. Capillary margination +/- thromboses C4d +
III. Arterial (v3)
C4d+
Renal Pathology
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Banff 97 Classification of Renal allograft Rejection
Updated 2001
3. Borderline changes: Suspicious for acute
cellular rejection
Foci of mild tubulitis
1 – 4 mononuclear cells per tubular cross section
No significant interstitial inflammation
Renal Pathology
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Banff 97 Classification of Renal allograft Rejection
Updated 2001
4. Acute/Active Cellular Rejection
T-cell mediated rejection
Type (Grade)
IA.
IB.
Significant interstitial infiltration, foci of moderate
tubulitis
Significant interstitial infiltration, foci of severe
tubulitis
IIA.
IIB.
Mild to moderate intimal arteritis
Severe intimal arteritis
III.
Transmural arteritis and or fibrinoid necrosis
Renal Pathology
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Banff 97 Classification of Renal allograft Rejection
Updated 2001
5. Chronic/sclerosing allograft nephropathy
Fibrosing changes in the allograft +/features of alloimmune injury
Grade
Histopathological findings
I.
Mild interstitial fibrosis and tubular atrophy +/changes suggesting chronic rejection
II.
Moderate interstitial fibrosis and tubular atrophy
+/- changes suggesting chronic rejection
III.
Severe interstitial fibrosis and tubular loss +/changes suggesting chronic rejection
Renal Pathology
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Banff 97 Classification of Renal allograft Rejection
Updated 2001
6. Other
Changes not due to rejection
Polyoma virus infection
De-novo and recurrent renal disease
Renal Pathology
Polyoma VN vs.
Acute Cellular
Rejection
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Widespread
infiltrates and focal
viral infection
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Expression of MHC
Class II antigen on
tubular epithelial
cells
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C4d deposition in the
peritubular
capillaries
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Renal Pathology
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Renal Pathology
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Renal Diseases that Recur in Transplant Kidney
Usual
Dense deposit D
Immunotactoid/Fibrillary
Diabetes Mellitus
Common
IgAN
HUS
HSP
FSGS - Primary
MPGN Type I
Amyloid
Pauci-immune
Renal Pathology
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Renal Diseases that Recur in Transplant Kidney
Rare
Anti-GBM disease
Systemic Lupus
No Recurrence
Classical HUS
Postinfectious GN
Secondary and familial FSGS
Hereditary nephritis