renal disease in zellweger s syndrome - echo360 · the spectrum when all goes wrong active disease...
TRANSCRIPT
Renal Pathology from A to Z
IgA nephropathy
Renal disease in Zellweger’s syndrome
Pathologists “Read”
the Slides
BUT…..
Patients Do Not
Read
the Textbook
•Glomerulus
•Tubules
•Vessels
•Interstitium
•
•
•All of the above
What Can Go Wrong in the Kidney?
What can go wrong,
will go wrong
Murphy’s Law
The Spectrum When All Goes Wrong
Active disease End Stage Kidney
Proliferation
Necrosis
Sclerosis
Fibrosis
Glomerulus
Cells Processes
Podocyte
Endothelial
Mesangial
Proliferation
Necrosis
Sclerosis
Deposits
Mechanisms of Renal Disease
Glomerulus-
•podocyte/GBM injury
•immune complex deposition
Glomerulus and/or vessels-
•hemodynamic
•thrombotic
•metabolic
•deposition of abnormal proteins
Tubules-
•ischemia
•immune
•inflammation
•infection
•toxic
Mechanisms of Renal Disease
Glomerulus-
•podocyte/GBM injury
• Idiopathic (or associated with
e.g. drug reaction)
• Nephrotic range proteinuria
• Normal light microscopy
• Foot process effacement by EM
Minimal Change Disease
• Idiopathic
• Nephrotic range proteinuria
• Glomerulosclerosis in
focal/segmental pattern
• Foot process effacement
• No immune complexes
FSGS
• Juxtamedullary lesions early
• Focal - > 25 glomeruli optimal
sample
• Peripheral, hilar, and mixed
FSGS Distribution
• FSGS, nos
• FSGS, collapsing
• FSGS, cellular
• FSGS, tip
• FSGS, hilar
Columbia FSGS Classification
D’Agati, Fogo, Bruijn, Jennette, AJKD 2004
• Collapse glomerular tuft, with
overlying proliferating GVEC
• Disproportionately severe, cystic
tubular lesions
Collapsing Glomerulopathy
Collapsing Glomerulopathy
Possible Etiologies
• Pamidronate treatment
• Ischemia
• Calcineurin inhibitor
• HIV
• Parvovirus
• Idiopathic
• SLE
• Other
Tip Lesion
•Sclerosis/adhesion at
proximal tubular pole
•Varying endocapillary proliferation
• “Bad” immune complex disease-
• diagnose by IF, EM
• Healed, chronic pauciimmune GN-
• broad-based scars, fibrocellular crescents
• Secondary scarring linked to hypertension-
• severe vascular lesions, subtotal FPE
• Secondary scarring linked to hypertension-
• Chronic pyelonephritis- geographic scarring
Secondary Glomerulosclerosis
Mechanisms of Renal Disease
Glomerulus-
• Immune complex deposition: • mesangial
• subepithelial
• subendothelial
Immune Complex Location
Determines the Reaction
• Mesangial–
• mesangial proliferation (e.g. IgAN, mesangial
LN)
• Subepithelial-
• GBM reaction—spikes (e.g. MN)
• Subendothelial-
• endocapillary proliferation, new matrix next to
deposits , interposed cells, tramtracking (e.g.
MPGN)
IgA Nephropathy
•Mesangial deposits
•Varying mesangial expansion
±endocapillary proliferation
±sclerosis
±crescents
•Poor prognostic indicators:
•Mesangial hypercellularity
•Endocapillary proliferation
•Segmental sclerosis
•Tubulointerstitial fibrosis >25%
Robert I et al, Cattran D et al, KI 2009
Oxford Classification of
IgA Nephropathy
•Subepithelial deposits
•IgG, C3
•Varying GBM reaction, silver stain
with spikes, lucencies on tangential
sections
±sclerosis
Membranous Nephropathy
•Proliferative, exudative (PMNs)
•Subepithelial hump-type deposits
±crescents
•IgG/C3
•May be IgA dominant with Staph
infection
Postinfectious GN
Membranoproliferative GN, Type I
•Endocapillary proliferation
•GBM split appearance
•Subendothelial deposits
•IgG/C3
Lupus Nephritis
• Immune complexes
(anywhere!)
• All Igs, C3, C1q
• Reticular aggregates
The diagnosis of SLE is NOT
made by renal biopsy
RATHER
Renal biopsy defines the TYPE
of renal lesion in a patient with
SLE
Abbreviated ISN/RPS classification of
lupus glomerulonephritis
Class I Minimal mesangial LGN
Class II Mesangial proliferative LGN
Class III Focal LGN
Class IV Diffuse segmental (IV-S) or global (IV-G) LGN
Class V Membranous LGN
Class VI Advanced stage LGN
Activity vs. Chronicity
Endocapillary proliferation Glomerulosclerosis
Leukocyte infiltration
Necrosis
*Cellular crescents Fibrous crescents
Interstitial nephritis Tubular atrophy
*Interstitial fibrosis
Lupus Nephritis • Nephritic - proliferative form
(subendothelial deposits)
• Bad prognosis
• Nephrotic - membranous form
(mostly subepithelial deposits)
• Chronic, low grade
• Minor urinary abnormalities- mesangial
proliferation due to mesangial deposits
Mechanisms of Renal Disease
Glomerulus- • Complement dysregulation
C3 glomerulopathies: • Dense deposit disease
• C3 glomerulonephritis
Dense Deposit Disease
(membranoproliferative GN, Type II)
•Endocapillary proliferation
•GBM splitting
•C3
•Dense transformation by EM
•Mesangial/endocapillary proliferation
•Mesangial, subendothelial deposits
•C3 only/dominant by IF
•Underlying complement abnormality
C3 Glomerulonephritis
Crescentic GN • Rapidly progressive GN -to ESRD quickly
• Disease-specific IF findings:
-Immune complex GN-
disease specific IF +
typically BAD deposits
-Anti-GBM-
linear IgG along GBM
-Pauciimmune-
neg IF
Granulomatosis with polyangiitis vs
Microscopic polyangiitis vs renal limited
Dr. Ernest W. Goodpasture
Mechanisms of Renal Disease
Glomerulus-
•Abnormal protein deposition
• MIDD
• Amyloid (AL, other)
• Cryoglobulin
• Other substructured deposits
LCDD
• Nodular glomerulosclerosis
• Granular, amorphous deposits -
glomeruli and tubules
Amyloid
• Congo-Red positive randomly
arranged fibrils in glomeruli,
vessels
• AL >> AA in kidney
Classification of Amyloidoses
Abbreviation Subunit Disease
AL (AH) Light chain
(rarely heavy chain)
Plasma cell dyscrasias
AA Serum amyloid A protein
(SAA)
Chronic inflammatory
states
Beta2 microglobulin Ab2M CKD-dialysis-
associated
Afib Fibrinogen Familial
Ab b protein Alzheimer
ALect2 Leukocyte chemotactic
factor
Renal/liver
Alys Lysozyme Familial
Agel Gelsolin Familial
Acys Cystatin C Familial
Apo A I/II or IV Apolipoprotein Kidney/(medulla for
I/IV)
Varying Deposits Can Occur
in a Given Patient
• LCCN + LCDD
• LCCN + AL amyloid
• Very very rare:
LCDD + AL amyloid
Cryoglobulin
• Proliferative, mesangial or MPGN-
type
• Type I - organized
• Type II, III - short, fibrillar
substructure
Substructured Deposits
Fibrillary GN and Immunotactoid
Glomerulopathy
• Fibrillary GN-
mesangial/membranoproliferative, polyclonal
IgG, fibrils by EM
• Immunotactoid GP- mesangial proliferative,
often clonal Ig, microtubular substructure
Lesions of Renal Disease
•Thick GBM+ proteinuria
Diabetic Nephropathy
Lesions of Renal Disease
•Segmental sclerosis
•Proteinuria
•Hematuria
Lesions of Renal Disease
•Crescents
•Proteinuria
•Hematuria
Lesions of Renal Disease
•GBM splitting
•±Proteinuria
•±Hematuria
What is it?
London, Saturday, Nov. 1st, 1845
Dear Dr. Jones,
The tube contains urine of very high specific gravity; when
boiled it becomes highly opake; on the addition of nitric acid it
effervesces, assumes a reddish hue, becomes quite clear, but, as
it cools, assumes the consistence and appearance which you
see: heat reliquifies it. What is it?
Dr. Thomas Watson
Dr. William Mcintyre