Renal pathology tutorial for nephrologists

1. Mesangial proliferative GN

2. • Mesangioproliferative pattern of glomerular
injury is characterized by the expansion of
mesangial matrix and the mesangial
hypercellularity. These changes can occur in
immune complex-mediated diseases, such as
IgA nephropathy or class II lupus nephritis or
non-immune diseases such as early diabetic
glomerulosclerosis, and some forms of
minimal change disease and primary focal
sclerosis.

3. Lupus nephritis Class II
• Histopathology:
• Mesangioproliferative pattern of glomerular injury;
the mesangium is expanded and hypercellular
• The glomerular basement membranes are of
unremarkable thickness and texture
• The tubulointerstitium is usually unremarkable
• Immunofluorescence:
• There is 'full house' reactivity (reactivity for IgG,
IgM, and IgA), with granular deposits in the
mesangium

4. • Electron microscopy:
• Visceral epithelial cells: Unremarkable, and the foot processes are
well preserved. Sometimes a few subepithelial deposits can be
found
• Glomerular basement membranes: Usually of normal appearance
and texture
• Glomerular endothelial cells: May contain tubuloreticular
structures. Rare, small subendothelial electron-dense deposits can
be seen scattered in a few places; if large subendothelial deposits
are seen, the proliferative forms of lupus nephritis (classes III or IV)
should be strongly considered
• Mesangium: Expanded by increase in cellular elements and
extracellular matrix with sometimes large and confluent fine
granular, electron-dense deposits

7. IgA
• Histopathology:
• Light microscopic examination reveals a mesangioproliferative
pattern of glomerular injury (mesangial hypercellularity and
expansion of mesangial matrix)
• The glomerular basement membranes are of unremarkable
thickness and texture
• The tubulointerstitium is usually unremarkable
• Immunofluorescence:
• There is dominant reactivity for IgA in the mesangium; C3 may
be equally or less reactive. There is usually stronger reactivity for
lambda then for kappa light chains in the mesangial deposits.

8. • Electron microscopy:
• Visceral epithelial cells: Usually unremarkable, and
the foot processes are well preserved
• Glomerular basement membranes: May be thin; there
is a higher incidence of thin glomerular basement
membrane disease in IgA nephropathy than in any
other glomerular disease {6}
• Glomerular endothelial cells: Usually unremarkable,
and tubuloreticular structures are not seen
• Mesangium: Increase in cellularity and extracellular
matrix, with fine granular electron-dense deposits that
are sometimes large and confluent

11. Resolving PIGN
• Histopathology:
• Mesangial hypercellularity and expansion
• Neutrophils are not evident, endocapillary
proliferation is not present (or is minimal)
• Some of the glomeruli may appear unremarkable
• In some cases, inflammatory process does not resolve
and results in glomerular and tubulointerstitial scarring
• Immunofluorescence:
• Coarse granular C3 reactivity in the mesangium and
along the capillary loops

12. • Electron microscopy:
• Visceral epithelial cells: There may be focal effacement of
foot processes
• Glomerular basement membranes: Subepithelial deposits
may be still present, particularly in areas of mesangial
notch, but subendothelial deposits have resolved
• Glomerular endothelial cells: May show non-specific
changes; tubuloreticular structures are not seen
• Mesangium: Increase in cellularity and extracellular
matrix, with sometimes large and confluent fine granular
electron-dense deposits; mesangial deposits are
predominant in resolving phase of the disease

15. Fibrillary GN
• Fibrillary glomerulopathy is characterized by
progressive clinical course, variable histologic
patterns (most commonly
membranoproliferative or
mesangioproliferative), with extracellular
deposition of Congo red negative material,
ultrastructurally consisting of non-branching,
randomly arranged microfibrils 12-30 nm in
diameter, usually with polyclonal IgG4
immunofluorescence reactivity.

16. • Etiology:
• Unclear etiology; fibrillary GN is only rarely associated with B-cell
neoplasias while the link is stronger in cases of immunotactoid
glomerulopathy {1}
• Clinical:
• Occurs more commonly in older patients (very rare in children)
and Caucasians
• There is usually nephrotic range proteinuria; other presenting
symptoms vary, including nephrotic syndrome, acute renal failure,
rapidly progressive nephritis, chronic renal insufficiency
• Outcome may be dependent on histologic pattern of injury {2}

17. • Histopathology:
• Commonly, there is mesangial expansion with increased mononuclear
inflammatory cells and matrix and peripheral capillary loop thickening (MPGN-like
pattern of injury); sometimes, the predominant pattern is mesangioproliferative (if
the deposition is not involving capillary loops) or even less commonly,
membranous, diffuse proliferative, or sclerosing patterns may be seen {2}
• Proliferative changes, such as increased endocapillary proliferation or crescent
formation, are uncommon but occur
• Congo red stain is negative
• Silver stain may reveal “moth eaten” appearance (non-reactive deposits admixed
with reactive matrix)
• Immunofluorescence:
• There is polyclonal deposition of IgG (most often IgG1 or IgG4) and C3 in the
mesangium and along the peripheral capillary loops; in less than 10% of cases, the
reactivity will be of monoclonal IgG; in very rare cases there will be no
immunoglobulin reactivity.

18. • Electron microscopy:
• Visceral epithelial cells: Focal, sometimes marked
effacement of visceral epithelial cell foot processes
• Glomerular basement membranes: Usually marked
thickening of the membranes with extensive fibrillary
deposits; the deposition extends to subepithelial,
subendothelial, and paramesangial spaces. The fibrils are
non-branching, randomly oriented, 12-30 nm in diameter
• Glomerular endothelial cells: Show loss of fenestrations
and other non-specific changes; they do not contain
tubuloreticular structures
• Mesangium: Usually expanded by matrix and organized
fibrillary deposits

22. Immunotactoid Glomerulopathy
• Immunotactoid glomerulopathy is a glomerular disease
characterized by deposition of abnormal proteins
(paraproteins) that are Congo red negative by light
microscopy and show microtubular or fibrillary
substructure by electron microscopy. The microtubules
are usually greater than 30 nm in diameter, sometimes
with central core, and are arranged parallel to the
glomerular basement membranes. There is usually
monoclonal immunoglobulin reactivity by
immunofluorescence. Clinically, immunotactoid
glomerulopathy is strongly associated with B-cell
lymphoproliferative disorders.

23. • Etiology:
• Deposition of abnormal monoclonal protein in
patients with paraproteinemia and lymphoproliferative
disorder
• Clinical:
• Usually occurs in patients over 60 years of age
• Usually presents with nephrotic range proteinuria;
other presenting symptoms vary, from nephrotic
syndrome, hematuria, acute renal failure, rapidly
progressive nephritis, chronic renal insufficiency

24. • Histopathology:
• Commonly, there is mesangial expansion with increased mononuclear
inflammatory cells and matrix and peripheral capillary loop thickening
(MPGN-like pattern of injury); rarely, the predominant pattern can be
mesangioproliferative (if the deposition is not involving capillary loops) or,
even less commonly, predominantly membranous
• Proliferative changes, such as increased endocapillary proliferation or
crescent formation, can be seen on rare occasions
• Congo red stain is negative
• Silver stain may reveal “moth eaten” appearance (non-reactive deposits
admixed with reactive matrix)
• Immunofluorescence:
• Monoclonal (kappa or lambda) reactivity of immunoglobulins (usually
IgG)

25. • Electron microscopy:
• Visceral epithelial cells: Focal, sometimes marked effacement of
visceral epithelial cell foot processes
• Glomerular basement membranes: Microtubular deposits,
frequently in parallel arrangements, can be seen in subepithelial
and intramembranous locations, extending to the paramesangial
and mesangial compartment; the basement membrane can be
affected with deposits in various degrees. The fibrils or
microtubules are non-branching, usually greater than 30 nm (10-90
nm) in diameter
• Glomerular endothelial cells: Show loss of fenestrations and other
non-specific changes; they do not contain tubuloreticular structures
• Mesangium: Usually expanded by matrix and organized
microtubular deposits

28. Early diabetic glomerulosclerosis
• Histopathology:
• In early diabetic glomerulosclerosis, there is mesangial expansion due to increase in amount of
matrix, with or without mesangial hypercellularity. There are no Kimmelstiel-Wilson nodules at this
stage of disease
• Peripheral capillary loops are usually of normal thickness and microaneurysms are not seen in
early stages
• Insudative lesions are usually not seen (fibrin cap, capsular drop)
• Mild patchy tubular atrophy and interstitial fibrosis and non-specific, predominantly
mononuclear cell inflammatory infiltrate
• Various degrees of vascular sclerosis and hyalinosis
• In early diabetic change, findings are milder, with mild mesangial sclerosis and mild arteriolar
hyalinosis; glomerular hypertrophy is probably the earliest sign of diabetic renal pathology
• Congo red stain is negative
• Immunofluorescence:
• Mild linear reactivity for albumin and IgG along the capillary loops; no immune deposits

29. • Electron microscopy:
• Visceral epithelial cells: Focal effacement of visceral
epithelial cell foot processes, in the absence of
electron-dense deposits
• Glomerular basement membranes: Usually of normal
thickness or slightly thickened
• Glomerular endothelial cells: Various non-specific
changes; do not contain tubuloreticular structures
• Mesangium: Normal cell elements and expansion of
extracellular matrix in the absence of electron-dense
deposits

31. Minimal Change Disease
• Can have some mesangial hypercellularity