Fibrillary Glomerulonephritis

Slide 1 · Fibrillary Glomerulonephritis

A clinicopathologic diagnosis based on organized glomerular deposits

Light microscopy · immunofluorescence · electron microscopy · DNAJB9

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning goals: Recognize, distinguish, integrate

Define fibrillary glomerulonephritis (FGN) and the location of its deposits.

Explain the characteristic light-microscopic and immunopathologic findings.

Interpret the diagnostic roles of Congo red, DNAJB9, and ultrastructure.

Distinguish FGN from amyloid, immunotactoid and C3-dominant diseases.

Link biopsy findings to proteinuria, hematuria and renal function.

Slide 3 · FGN is defined by organized glomerular fibrils

A pathologic entity, not a light-microscopic pattern alone

Where

Mesangial regions and glomerular capillary walls

What

Nonamyloid-type fibrillar deposits, typically Congo-red–negative

How identified

DNAJB9 tissue staining with IF and ultrastructural correlation

Slide 4 · Clinical syndrome and biopsy must be integrated

Proteinuria, hematuria or declining kidney function

Kidney biopsy with LM, IF and EM

DNAJB9-positive organized deposits support FGN

Slide 5 · FGN is uncommon among native kidney biopsies

A rare glomerular disorder

A 2019 review reports FGN in fewer than 1% of native kidney biopsies; Rarity increases the value of an integrated biopsy diagnosis.

Slide 6 · Etiology remains incompletely established

What is established

FGN contains fibrillary glomerular deposits.

Deposits commonly contain immunoglobulin and complement.

DNAJB9 is strongly associated with deposits.

What remains uncertain

The initiating molecular event.

Whether DNAJB9 is causal or a recruited component.

Mechanisms governing the rate of renal progression.

Slide 7 · FGN sits within the glomerular disease framework

Injury site

Glomerular tuft and filtering capillary walls

Pattern

May produce mesangial, MPGN or crescentic changes

Syndrome

Can produce nephrotic and nephritic manifestations

Slide 8 · A glomerulus has distinct sites of injury

Capillary loops

Mesangium

Simplified glomerular schematic — not histology

Slide 9 · FGN deposits occupy two critical compartments

Mesangial deposits

Capillary wall deposits

Simplified glomerular schematic — not histology

Slide 10 · The capillary wall is a three-layer filter

Capillary lumen

Fenestrated endothelium

Glomerular basement membrane

Podocyte foot processes

Urinary space

Slide 11 · Glomerular barrier damage leads to proteinuria

Deposits and glomerular capillary injury

Increased passage of plasma proteins

Proteinuria; Nephrotic syndrome may develop

Slide 12 · Inflammatory injury can produce hematuria

Glomerular inflammation or capillary injury

Erythrocytes escape into urinary space

Hematuria ± red-cell casts in nephritic syndromes

Slide 13 · A pathologic pattern is not a single etiology

Membranoproliferative pattern

Describes mesangial proliferation and capillary-wall remodeling.

Can be produced by distinct disease mechanisms.

An appearance, not itself proof of FGN.

Fibrillary glomerulonephritis

A deposit-defined glomerular entity.

May exhibit an MPGN pattern on LM.

Requires immunopathologic identification.

Slide 14 · FGN frequently has an MPGN-type lesion

Light microscopy may show a membranoproliferative configuration.

Mesangial expansion/proliferation and altered capillary loops can coexist.

GBM remodeling is a tissue response to underlying glomerular injury.

An MPGN biopsy pattern should prompt etiologic classification.

Slide 15 · Double contours indicate capillary-wall remodeling

Subendothelial deposits / endothelial insult

New basement-membrane material and interposition

A double-contour “tram-track” pattern

Slide 16 · Mesangial changes can reshape the tuft

Cellularity

Mesangial proliferation increases tuft cellularity

Matrix

Expanded matrix emphasizes mesangial regions

Lobulation

Capillary-loop architecture may become accentuated

Slide 17 · Crescents are another possible FGN pattern

Severe glomerular capillary injury

Leakage of fibrin and inflammatory mediators

Extracapillary cellular crescent formation

Slide 18 · A crescent is a response, not a unique diagnosis

What a crescent means

Severe capillary-wall injury.

Cell accumulation in Bowman space.

Possible rapidly progressive course.

What it does not mean

Not exclusively FGN.

Not sufficient to classify immune mechanism.

Not a replacement for IF, EM and clinical workup.

Slide 19 · Light microscopy does not establish FGN alone

Mesangial injury

Can occur in other immune-mediated glomerular diseases

MPGN pattern

Shared by immunoglobulin-related and complement-related disorders

Crescents

Shared by several rapidly progressive glomerulonephritides

Slide 20 · The biopsy is interpreted by three modalities

Light microscopy

Defines the pattern and severity of glomerular injury

Immunofluorescence

Identifies immunoglobulins, light chains and C3

Electron microscopy

Characterizes fibril organization and location

Slide 21 · Congo red is usually negative in FGN

Characteristic result

Typical FGN deposits lack Congo-red positivity.

This is a useful distinction from amyloid.

Interpret together with ultrastructure.

Diagnostic limitation

A negative stain does not prove FGN.

Rare congophilic variants are described in reviews.

DNAJB9 and deposit morphology remain important.

Slide 22 · The Congo-red result is one diagnostic dimension

Fibrillary deposits detected

Congo red typically negative

DNAJB9, Ig profile and EM establish identity

Slide 23 · Immunofluorescence usually identifies IgG

Deposits typically react for IgG.

The staining reflects material in mesangial and capillary-wall regions.

An immunoglobulin-positive pattern must be interpreted alongside EM.

IgG deposition alone is not specific for FGN.

Slide 24 · IgG4 is frequently represented in deposits

Subclassification finding

IgG4 often predominates among IgG subclasses.

The observation helps characterize the deposits.

FGN remains a tissue-level diagnosis.

Avoid overinterpretation

IgG4 is not a standalone diagnostic test.

Subclass patterns vary across cases.

IgG4 positivity does not explain all disease mechanisms.

Slide 25 · Complement C3 commonly accompanies IgG

Glomerular IgG deposition

C3 may be detected in the same involved compartments

An IgG/C3 pattern supports an immune-deposit process

Slide 26 · Both light chains are usually detectable

κ light chain

Often detectable within glomerular deposits

λ light chain

Often detectable within the same deposits

Interpretation

Concordant detection supports a polytypic pattern

Slide 27 · Monotypic-appearing deposits need verification

Why the issue arises

FGN is often polyclonal but exceptions exist.

Apparent light-chain restriction complicates classification.

Single observations can be misleading.

Practical response

Correlate with DNAJB9 and ultrastructure.

Consider additional tissue studies as appropriate.

Do not equate restriction with systemic malignancy.

Slide 28 · Electron microscopy reveals disordered fibrils

Original diagram — disordered fibril orientation; Not electron microscopy

Slide 29 · FGN fibrils are nonbranching and randomly oriented

Fibrils lie without a uniform parallel arrangement.

The fibrils do not form regular hollow-core microtubules.

This ultrastructural organization helps distinguish other deposit diseases.

Electron microscopy assesses both deposit type and localization.

Slide 30 · FGN fibrils have a characteristic size range

Approximately 15–25 nm in diameter

Reported in a 2019 review (mean near 20 nm). Size is a diagnostic clue, not a substitute for full ultrastructural interpretation.

Slide 31 · Electron-dense fibrils involve mesangium and wall

Mesangial deposits

Capillary wall deposits

Simplified glomerular schematic — not histology

Slide 32 · Amyloid is the primary fibrillar alternative

Feature

FGN

Amyloidosis

Congo red

Usually negative

Typically positive

Fibrils

Larger, disordered

Typically thinner fibrils

Immunophenotype

Usually IgG/C3 with DNAJB9

Variable by amyloid type

Confirmatory step

DNAJB9 + EM

Amyloid typing and morphology

Slide 33 · Immunotactoid deposits show another architecture

Finding

FGN

Immunotactoid GN

Ultrastructure

Random fibrils

Organized microtubules

Hollow center

Not characteristic

May be evident

Fibril dimensions

Generally smaller

Generally larger structures

DNAJB9

Usually positive

Typically negative

Slide 34 · DNAJB9 is a tissue biomarker of FGN

Identity

DnaJ heat-shock protein family member B9

Location

Present within characteristic glomerular deposits

Practical value

Immunohistochemical staining helps identify FGN

Slide 35 · DNAJB9 immunohistochemistry strengthens diagnosis

DNAJB9 has high diagnostic sensitivity and specificity in studied biopsy series.

Strong glomerular deposit staining supports FGN in the correct setting.

The assay is particularly helpful when deposit morphology is difficult to classify.

Interpret antibody staining with light microscopy and immunofluorescence.

Slide 36 · DNAJB9 is diagnostic, not necessarily pathogenic

Supported

DNAJB9 accumulates in FGN deposits.

Tissue immunostaining is diagnostically informative.

It belongs to a stress-response protein family.

Not established

That DNAJB9 triggers initial injury.

That tissue positivity defines treatment response.

A proven DNAJB9-targeted therapy.

Slide 37 · EM and DNAJB9 give complementary information

Question

Electron microscopy

DNAJB9 IHC

Are fibrils present?

Directly characterizes them

Does not visualize fibrils

How are deposits arranged?

Shows orientation/location

Shows tissue localization

Is this likely FGN?

Morphology supports identity

Biomarker supports identity

Can tests replace context?

No

No

Slide 38 · Integrated diagnosis follows evidence in sequence

Identify lesion pattern on light microscopy

Characterize IgG, C3 and κ/λ by immunofluorescence

Assess Congo red and DNAJB9 staining

Use electron microscopy to evaluate organized fibrils

Correlate with clinical findings and competing diagnoses

Slide 39 · Pitfall: Reporting MPGN without its cause

Incomplete report

“Membranoproliferative GN” describes architecture.

It does not specify deposit composition.

It may obscure a treatable alternate process.

More informative report

Describe the MPGN pattern.

Add IF, DNAJB9 and EM characterization.

Classify the underlying glomerulopathy.

Slide 40 · Pitfall: A Congo-negative stain is nonspecific

Unjustified leap

Congo red negative → FGN.

Overlooks other Congo-negative deposits.

Misses required immunopathologic context.

Preferred reasoning

Look for organized fibrils.

Assess immunoglobulin/C3 pattern.

Confirm with DNAJB9 and EM where available.

Slide 41 · Pitfall: Apparent monoclonality is complex

Some reported FGN cases display monotypic deposits.

Light-chain restriction should prompt careful technical review.

Potential systemic paraprotein disease requires clinical correlation.

The finding does not automatically establish a monoclonal gammopathy.

Slide 42 · Pitfall: Interpretation without electron microscopy

What can be established

LM shows a glomerular injury pattern.

IF defines IgG/C3 and light chains.

DNAJB9 strongly supports FGN.

What remains less direct

Fibril architecture is not visualized.

Atypical deposits may require EM.

Do not claim unseen ultrastructural findings.

Slide 43 · Differentiate C3-dominant glomerulopathy

Feature

FGN

C3 glomerulopathy

IF emphasis

IgG plus C3 common

C3-dominant staining

Core mechanism

Pathogenesis unresolved

Alternative complement dysregulation

Deposits

Fibrillary, DNAJB9-associated

C3-rich deposits

Workup focus

DNAJB9/EM/deposit type

Complement studies + EM

Slide 44 · Differentiate immune-complex MPGN

Feature

FGN with MPGN pattern

Immune-complex MPGN

Light microscopy

May show MPGN

Shows MPGN

Deposit structure

Characteristic fibrils

Typically nonfibrillar dense deposits

IF

IgG, C3 often present

IgG, C3 often present

Discriminator

DNAJB9 and fibrillar EM

Etiology + nonfibrillar EM

Slide 45 · Differentiate crescentic anti-GBM disease

Feature

Crescentic FGN

Anti-GBM GN

Crescents

Possible

Commonly prominent

IgG pattern

Deposit-associated

Linear GBM staining

EM

Fibrillar deposits

Not defined by FGN fibrils

Serology

Correlate clinically

Anti-GBM antibodies relevant

Slide 46 · The differential is decided by multiple tests

Amyloid

Congo red, typing, fibril morphology

Immunotactoid disease

Microtubular organization on EM

Complement-mediated GN

C3-dominant immunofluorescence and workup

Slide 47 · Nephrotic syndrome can be a clinical presentation

Glomerular filtration barrier damage

Sustained urinary loss of proteins

Proteinuria, hypoalbuminemia and edema

Slide 48 · FGN may cause a nephritic component

Hematuria reflects glomerular capillary injury.

More severe inflammatory injury may produce a crescentic pattern.

Nephritic and nephrotic features can coexist.

Syndrome designation is not a substitute for histopathologic classification.

Slide 49 · Renal insufficiency may progress over time

Persistent glomerular injury

Loss of functioning glomerular capillaries and scarring

Progressive decline in kidney function

Slide 50 · Histologic activity and chronic damage differ

Potentially active injury

Cell proliferation and inflammatory injury.

Crescents may reflect ongoing severe injury.

May influence urgency of assessment.

Chronic remodeling

Mesangial or capillary sclerosis.

Loss of functioning filtration surface.

Supports assessment of irreversible damage.

Slide 51 · Recurrence after transplantation is recognized

FGN can recur in kidney allografts.

Recurrence is established and subsequent reviews.

Recurrent deposits require accurate morphologic classification.

The possibility of recurrence does not preclude transplantation.

Slide 52 · Clinical associations are not universal causes

Reported associations

Autoimmune disease.

Hepatitis C infection.

Some malignancies or hematologic disorders.

Critical interpretation

Association is not proof of causation.

Many cases lack a proven associated condition.

Clinical investigation should be individualized.

Slide 53 · Therapeutic evidence remains limited

No universally established disease-specific regimen exists.

Supportive kidney-protective care addresses blood pressure and proteinuria.

Immunosuppressive approaches are reported, but outcomes are variable.

Management decisions require specialist clinical assessment.

Slide 54 · Case A: An MPGN pattern with IgG deposits

A patient has proteinuria and hematuria. Renal biopsy shows an MPGN pattern. IF detects IgG and C3.

Which tests would distinguish FGN from other causes of MPGN?

Slide 55 · Case A: Determine the deposited material

Assess DNAJB9 immunohistochemistry.

Examine the organization and location of deposits by EM.

Review κ/λ staining and Congo red.

The MPGN pattern itself cannot complete the diagnosis.

Slide 56 · Case B: Congo-red–negative fibrillary deposits

The biopsy contains disordered fibrils in the mesangium and capillary walls. Congo red is negative.

What additional pattern would strengthen a diagnosis of FGN?

Slide 57 · Case B: Recognize the immunopathologic profile

Polyclonal IgG deposits, often with IgG4 representation.

Concomitant C3 deposition.

Both κ and λ light chains usually present.

DNAJB9 immunostaining supports fibrillary GN.

Slide 58 · Case C: Crescents plus abnormal IF staining

A biopsy contains crescents and an unusual glomerular IgG staining pattern.

Why is a crescent count or IgG stain alone inadequate for classification?

Slide 59 · Case C: Integrate cause and injury pattern

Crescents mark severe glomerular injury but are not specific.

Examine IgG distribution and additional immune reactants.

Seek fibrillary material, DNAJB9 and EM confirmation when indicated.

Correlate with the rapidly progressive clinical course and serology.

Slide 60 · Case D: New allograft proteinuria

A recipient transplanted for biopsy-proven FGN develops new proteinuria and deterioration of allograft function.

Which prior disease-specific finding should remain in the differential?

Slide 61 · Case D: Consider recurrent FGN

FGN recurrence in kidney transplants is documented.

Clinical changes are not specific for recurrence.

Biopsy interpretation again requires LM, IF and deposit characterization.

DNAJB9 can help assess a suspected recurrent deposit disease.

Slide 62 · A complete FGN biopsy report integrates evidence

Describe light-microscopic pattern and chronic damage

Record IgG/C3 and κ/λ immunofluorescence findings

State Congo red and DNAJB9 findings

Describe fibrillar ultrastructure if actually assessed

Provide an integrated diagnosis with limitations

Slide 63 · The FGN diagnostic signature

Domain

Most characteristic finding

Deposits

Mesangial + capillary-wall fibrils

Light microscopy

Often MPGN and/or crescentic

Immunofluorescence

Usually polyclonal IgG, C3, κ and λ

Congo red

Typically negative

Tissue marker

DNAJB9 staining supports diagnosis

Clinical course

Proteinuria, hematuria, progressive dysfunction

Slide 64 · Questions that remain open in FGN

What initiates the formation of fibrillar deposits?

Why does DNAJB9 accumulate within deposits?

Which pathobiologic mechanisms predict progression?

Which therapies can reproducibly alter long-term outcomes?

Slide 65 · Core references and diagnostic reading

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. 2026. Chapter 20, pp. 815–836.

Rosenstock JL, Markowitz GS. Fibrillary Glomerulonephritis: An Update. Kidney Int Rep. 2019;4:917–922.

Nasr SH et al. DNAJB9 Is a Specific Immunohistochemical Marker for FGN. Kidney Int Rep. 2018;3:56–64.

Updates on the Diagnosis and Management of FGN. Adv Kidney Dis Health. 2024;31:374–383.