Lupus Nephritis

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Lecture topics

Why the kidney matters in systemic lupus
Deposit localization predicts dominant injury
Reduced renal function has structural correlates
Class III: Active cellular and capillary lesions
Class V: Membranous lupus nephritis
Thrombotic microangiopathy requires separate recognition
Case: Mesangial proliferation without capillary injury
Primary reference and scope

Slide index & full transcript (74 slides)

Text from the original slides, in presentation order. Diagrams and images remain in the viewer above.

Slide 1 · Lupus Nephritis

Immune-complex mechanisms · renal morphology · clinical correlations

Renal pathology teaching lecture

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Locate immune deposits within the glomerular filtration barrier and predict their injury patterns.

Distinguish the defining renal morphology of lupus nephritis classes I–VI.

Connect glomerular, tubulointerstitial, and vascular lesions with clinical syndromes.

Interpret clinicopathologic vignettes without treating urine findings as a histologic class.

Slide 3 · Why the kidney matters in systemic lupus

Systemic lupus erythematosus (SLE) produces heterogeneous renal lesions.

Glomerular immune-complex injury is a major mechanism.

Tubulointerstitial and vascular injury may accompany glomerulonephritis.

Renal involvement is more than glomerulonephritis.

Slide 4 · Anatomic compartments at risk

Within the glomerulus

Mesangium

Glomerular capillary walls

Endothelial and epithelial compartments

Beyond the glomerulus

Tubules and interstitium

Tubular/peritubular capillary basement membranes

Renal vessel intima and media

Slide 5 · The glomerular filtration barrier

Capillary lumen

Endothelium

Subendothelial zone

Glomerular basement membrane

Subepithelial zone

Podocyte / urinary space

Endothelium faces circulating immune reactants.

The basement membrane separates endothelium from podocytes.

Deposit position helps determine the inflammatory response.

Slide 6 · Systemic immune dysregulation precedes renal injury

Nuclear antigen persistence + defective tolerance

Self-reactive B/T-cell response

Autoantibody production

Antigen–antibody complexes

Schematic — directional teaching model; Not a patient-specific pathway.

Slide 7 · An amplifying lupus immunologic circuit

Nuclear antigen burden

Compartment

Predominant pathologic response

Typical lupus association

Mesangium

Mesangial immune deposition ± proliferation

Classes I–II

Subendothelial

Endocapillary inflammation and proliferative injury

Classes III–IV

Subepithelial

Capillary-wall thickening and proteinuria

Class V

Slide 14 · Immunoreactants in lupus nephritis

Immunoglobulin G is commonly present in deposited immune complexes.

IgA and IgM frequently accompany IgG.

Complement components C3 and C1q are also often detected.

Multiple immune reactants can coexist.

Slide 15 · The meaning of granular immunofluorescence

Discrete immune-complex deposits yield a granular distribution.

Capillary-wall deposits

Mesangial deposits

Mixed distribution

Schematic fluorescence clusters; Not a real immunofluorescence photomicrograph.

Slide 16 · Light microscopy, IF, and EM answer different questions

Technique

Primary question

Example in lupus nephritis

Light microscopy

What architectural injury is present?

Proliferation, necrosis, sclerosis

Immunofluorescence

Which immune reactants and distribution?

Granular immunoglobulin/complement

Electron microscopy

Exactly where are deposits?

Mesangial, subendothelial, subepithelial

Slide 17 · Complement recruits inflammatory effectors

Immune-complex deposition

Complement activation

Chemotactic mediators

Leukocyte infiltration

Schematic — directional teaching model; Not a patient-specific pathway.

Slide 18 · Cells amplify glomerular injury

Recruited leukocytes

Neutrophils release proteases and reactive oxygen species

Monocytes/macrophages release inflammatory mediators

Inflammation can damage capillary walls

Intrinsic glomerular cells

Mesangial cells produce cytokines and growth factors

Endothelial/mesangial proliferation narrows capillary lumina

Persisting stimulation promotes remodeling

Slide 19 · Acute inflammation versus persistent injury

Immune deposition

Active glomerular injury

Repeated episodes of inflammation

Remodeling and glomerular sclerosis

Schematic — directional teaching model; Not a patient-specific pathway.

Slide 20 · Clinical presentations form a spectrum

Urinary findings

Microscopic or gross hematuria

Proteinuria of varying degree

Red cell casts with active nephritic injury

Renal/vascular effects

Nephritic or nephrotic syndrome

Rapidly progressive glomerulonephritis

Reduced renal function and hypertension

Slide 21 · Hematuria reflects glomerular capillary injury

Active capillary-wall damage permits erythrocytes to enter the urine.

Hematuria may be microscopic or macroscopically visible.

Red cell casts support an intrarenal nephritic sediment.

Urine findings identify a syndrome, not a class.

Slide 22 · Proteinuria: Link morphology to permeability

Capillary-wall or podocyte-region injury

Impaired filtration-barrier selectivity

Increased urinary protein loss

Heavy proteinuria / nephrotic syndrome

Schematic — directional teaching model; Not a patient-specific pathway.

Slide 23 · Reduced renal function has structural correlates

Inflammation, capillary narrowing, and necrosis can impair filtration.

Rapidly progressive forms may feature extensive crescents.

Chronic glomerular scarring reduces the surviving filtration surface.

Active injury and chronic scarring must be distinguished.

Slide 24 · Interpreting a kidney biopsy

Light microscopy: Map inflammation, necrosis, proliferative lesions, sclerosis

Immunofluorescence: Document immune-reactant distribution

Electron microscopy: Localize electron-dense deposits

Integrate glomerular, tubulointerstitial, and vascular findings

Slide 25 · The six morphologic patterns

Class

Name

Dominant defining feature

Minimal mesangial

Deposits; normal light microscopy

Mesangial proliferative

Mesangial cellular/matrix increase

III

Focal

<50% glomeruli affected

Diffuse

>50% glomeruli affected

Membranous

Subepithelial deposits; capillary thickening

Advanced sclerosing

≥90% globally sclerosed glomeruli

Slide 26 · Morphologic classes can overlap or evolve

Distinct patterns are not immutable disease stages.

Classes may overlap, and a patient’s lesion can change over time.

Membranous lesions can coexist with proliferative classes.

Biopsy findings describe the sampled kidney at a particular time.

Avoid a rigid I → II → III → IV → V → VI progression.

Slide 27 · Class I: Minimal mesangial lupus nephritis

Schematic — not diagnostic histology.

Mesangial immune-complex deposits detected by IF or EM.

No structural abnormality on routine light microscopy.

Described as very uncommon.

Slide 28 · Why class I can escape light microscopy

Light microscopy

Glomerular architecture remains unremarkable

No required hypercellularity or capillary-wall thickening

IF and electron microscopy

Reveal mesangial immune deposits

Establish an immune-complex lesion despite normal LM

Slide 29 · Class II: Mesangial proliferative nephritis

Schematic — not diagnostic histology.

Mesangial cell proliferation is the defining change.

Mesangial matrix may also increase.

Granular mesangial Ig/complement deposition without active endocapillary inflammation.

Slide 30 · Class I versus class II

Feature

Class I

Class II

Mesangial deposits

Present on IF/EM

Light microscopy

No structural change

Mesangial proliferation ± matrix

Capillary inflammation

Not defining

Absent as class-defining lesion

Slide 31 · Class III: Focal lupus nephritis

Illustrative 12-glomerulus sampling grid

4 / 12 schematic glomeruli affected

Fewer than 50% of glomeruli are involved.

Injured glomeruli may have segmental or global lesions.

Active lesions and scars may coexist.

Schematic — drawn glomeruli are not biopsy specimens.

Slide 32 · Segmental and global describe area within a tuft

Segmental lesion

Only a portion of one glomerulus is affected

Necrosis or scarring need not involve the whole tuft

Global lesion

An entire glomerular tuft is affected

The focal/diffuse distinction concerns how many glomeruli are involved

Slide 33 · Class III: Active cellular and capillary lesions

Schematic — not diagnostic histology.

Endothelial and mesangial cell swelling/proliferation.

Leukocyte accumulation and capillary necrosis.

Hyaline thrombi may be encountered.

Slide 34 · Necrosis can trigger crescent formation

Severe capillary-wall injury

Focal necrosis and inflammatory exudation

Extracapillary cellular proliferation

Crescent in Bowman space

Schematic — directional teaching model; Not a patient-specific pathway.

Slide 35 · Class III: Active nephritic sediment

Active focal lesions can manifest with hematuria and proteinuria.

Red cell casts are often present during active nephritis.

Presentation may extend to acute renal insufficiency.

Focal in distribution does not mean clinically trivial.

Slide 36 · Healing after focal proliferative injury

Proliferative inflammatory focus

Resolution of active injury

Complete healing OR residual scar

Segmental / global glomerular sclerosis

Schematic — directional teaching model; Not a patient-specific pathway.

Slide 37 · Class IV: Diffuse lupus nephritis

Illustrative 12-glomerulus sampling grid

9 / 12 schematic glomeruli affected

Greater than 50% of glomeruli are involved.

Lesions resemble those of class III but are more extensive.

Described as the commonest and most severe form.

Schematic — drawn glomeruli are not biopsy specimens.

Slide 38 · Class IV: Pronounced proliferative injury

Schematic — not diagnostic histology.

Endothelial, mesangial and epithelial cell proliferation.

Numerous glomeruli exhibit capillary inflammation.

Glomerular damage may progress toward sclerosis.

Slide 39 · Class IV: Crescentic disease can be extensive

Cellular crescents occupy Bowman space.

Crescents reflect a severe response to capillary injury.

Marked extracapillary proliferation may impair glomerular filtration.

A crescent is a lesion, not a separate lupus class.

Slide 40 · Wire loops are subendothelial immune deposits

Capillary lumen

Endothelium

Subendothelial zone

Glomerular basement membrane

Subepithelial zone

Podocyte / urinary space

Extensive subendothelial complexes thicken the capillary-wall profile.

Light microscopy may show a circumferential “wire-loop” appearance.

EM demonstrates corresponding electron-dense deposits.

Slide 41 · Correlating the wire-loop lesion across modalities

Observation

Interpretation

Technique

Circumferential capillary thickening

Wire-loop appearance

Light microscopy / PAS

Dense deposits beneath endothelium

Subendothelial immune complexes

Electron microscopy

Granular capillary immune reaction

Deposited immunoglobulin/complement

Immunofluorescence

Slide 42 · Class IV: Clinical expectations

Hematuria and proteinuria are usually present.

Hypertension is common in diffuse proliferative disease.

Renal dysfunction varies from mild to severe.

Extent and activity jointly influence the phenotype.

Slide 43 · Focal versus diffuse proliferative lupus nephritis

Feature

Class III

Class IV

Glomeruli involved

<50% in source

>50% in source

Type of active lesion

Proliferation, necrosis ± crescents

Similar lesions, more extensive

Clinical range

Mild urine changes to insufficiency

Often symptomatic; dysfunction common

Potential outcome

Healing or scarring

Scarring may develop

Slide 44 · Class V: Membranous lupus nephritis

Schematic — not diagnostic histology.

Diffuse capillary-wall thickening is characteristic.

Subepithelial immune complexes are central.

Mesangial deposits frequently accompany the lesion.

Slide 45 · How membranous remodeling forms

Subepithelial immune-complex deposition

New GBM-like matrix production

Thickening of capillary walls

Protein permeability / heavy proteinuria

Schematic — directional teaching model; Not a patient-specific pathway.

Slide 46 · Class V: Nephrotic presentation

Severe proteinuria or nephrotic syndrome is characteristic.

The lesion resembles membranous nephropathy morphologically.

The context of SLE and immune deposition establishes the lupus setting.

Membranous pattern ≠ absence of systemic autoimmunity.

Slide 47 · Membranous and proliferative patterns may coexist

Membranous component

Subepithelial deposits

Capillary-wall thickening

Often heavy proteinuria

Associated proliferative component

Focal or diffuse glomerular inflammation

Necrosis / crescents may coexist

Can add hematuria or functional decline

Slide 48 · Class VI: Advanced sclerosing nephritis

Schematic — not diagnostic histology.

At least 90% of glomeruli are globally sclerosed.

The definition describes extensive irreversible glomerular scarring.

Active deposits elsewhere do not replace the sclerosis criterion.

Slide 49 · Why global sclerosis reduces kidney function

Global destruction of glomerular tufts

Fibrous replacement / sclerosis

Loss of filtering surface

Chronic reduction in renal function

Schematic — directional teaching model; Not a patient-specific pathway.

Slide 50 · Classes I, II and VI: Contrasting disease states

Feature

Core identity

Silent mesangial deposits

Mesangial proliferation

Advanced global sclerosis

Diagnostic strength

IF/EM

LM + IF

LM assessment of scarring

Scope of injury

Minimal structural change

Mesangial expansion

≥90% globally scarred

Slide 51 · Classes III, IV and V: The crucial discrimination

Feature

III

Dominant pattern

Focal proliferative

Diffuse proliferative

Membranous

Deposit association

Subendothelial may occur

Prominent subendothelial

Subepithelial

Clinical cue

Hematuria ± renal decline

Nephritic + renal decline

Heavy proteinuria

Coexistence

May accompany V

May accompany III/IV

Slide 52 · Renal lesions extend beyond glomeruli

Tubulointerstitial disease

Interstitial inflammatory changes

Tubular/peritubular immune deposits

Occasionally predominant lesion

Vascular involvement

Intimal/media immune-complex deposition

Less frequent active vasculitis

Occasional thrombotic microangiopathy

Slide 53 · Lupus-associated podocytopathy is a distinct feature

Podocytopathy in association with class I–II patterns.

The morphology may resemble minimal change disease.

Do not force all marked proteinuria into class V without examining additional lesions.

A concurrent lesion may explain discordant manifestations.

Slide 54 · Thrombotic microangiopathy requires separate recognition

Thrombotic microangiopathy may accompany lupus-related renal injury.

It is not defined solely by the glomerular immune-deposit class.

A complete biopsy interpretation should record vascular injury independently.

Vascular pathology adds information beyond class I–VI.

Slide 55 · Tubular and interstitial lupus injury

Tubulointerstitial abnormalities are frequent in lupus nephritis.

Rare cases have predominantly tubulointerstitial lesions.

Renal dysfunction therefore cannot be attributed only to glomerular tufts.

Inspect tubules, interstitium, and vessels.

Slide 56 · Immune deposits occur outside glomeruli

Systemic immune complexes

Tubular basement membranes

Peritubular capillary basement membranes

Local tubulointerstitial injury

Schematic — directional teaching model; Not a patient-specific pathway.

Slide 57 · B-cell aggregates in the renal interstitium

Well-organized interstitial B-cell follicles are occasionally present.

Associated plasma cells may serve as local autoantibody sources.

This finding emphasizes the immune activity of the renal interstitium.

The interstitium can be immunologically active.

Slide 58 · Renal vascular involvement

More frequent observation

Immune-complex deposition in arterial intima/media

May coexist with glomerular or interstitial involvement

Less common severe pattern

Active vasculitis with vessel-wall necrosis

Lesions may accompany thrombotic microangiopathy

Slide 59 · A whole-biopsy reporting framework

Glomerular class and extent: Mesangial, proliferative, membranous, or sclerosing

Active lesions: Inflammation, necrosis, crescents, immune deposits

Chronic lesions: Segmental/global sclerosis and fibrotic remodeling

Extraglomerular findings: Interstitial inflammation, deposits, vascular lesions

Slide 60 · Clinical manifestations follow lesion anatomy

Dominant lesion

Mechanistic consequence

Clinical expression

Necrotizing capillary injury

Erythrocyte passage into filtrate

Hematuria; red cell casts

Barrier / podocyte-region damage

Increased protein permeability

Heavy proteinuria

Diffuse capillary injury

Reduced effective filtration

Impaired kidney function

Extensive sclerosis

Loss of functional glomeruli

Chronic renal failure

Slide 61 · Activity and chronicity are different dimensions

Features of active injury

Endocapillary leukocytes / proliferation

Capillary necrosis

Cellular crescents

Features of established damage

Global or segmental sclerosis

Residual fibrotic remodeling

Reduced surviving filtration surface

Slide 62 · Biopsy morphology and phenotype may diverge

Classes overlap and may evolve over time.

Glomerular lesions can coexist with podocytopathy or vascular injury.

Urine abnormalities and renal function indicate impact; LM/IF/EM resolve anatomy.

Avoid assigning a class from symptoms alone.

Slide 63 · Case: Normal glomeruli on light microscopy

HYPOTHETICAL TEACHING CASE

Patient with established SLE.

LM: Glomeruli have no structural change.

IF/EM: Mesangial immune-complex deposits.

PATTERN AND EXPLANATION

Class I — minimal mesangial lupus nephritis.

The immune deposition is real, but routine light microscopy lacks defining structural change.

Slide 64 · Case: Mesangial proliferation without capillary injury

HYPOTHETICAL TEACHING CASE

Patient with established SLE.

LM: Increased mesangial cellularity and matrix.

IF: Granular mesangial immune deposits.

No active endocapillary inflammation.

PATTERN AND EXPLANATION

Class II — mesangial proliferative lupus nephritis.

The class is distinguished from class I by mesangial structural proliferation.

Slide 65 · Case: Necrotizing glomerulonephritis in a minority of glomeruli

HYPOTHETICAL TEACHING CASE

SLE with hematuria and red cell casts.

Biopsy: Segmental necrosis and crescents in 4 of 12 glomeruli.

PATTERN AND EXPLANATION

Class III — focal lupus nephritis.

Only a minority of glomeruli is affected; Necrosis and crescents indicate active proliferative injury.

Slide 66 · Case: Diffuse proliferation and wire loops

HYPOTHETICAL TEACHING CASE

SLE with hematuria, proteinuria, and impaired kidney function.

Biopsy: Extensive proliferative injury in 9 of 12 glomeruli; Subendothelial deposits.

PATTERN AND EXPLANATION

Class IV — diffuse lupus nephritis.

The extent exceeds half of sampled glomeruli; Wire loops reflect prominent subendothelial deposits.

Slide 67 · Case: Severe proteinuria with capillary thickening

HYPOTHETICAL TEACHING CASE

SLE with nephrotic-range urinary protein loss.

Biopsy: Diffuse capillary-wall thickening and subepithelial deposits.

PATTERN AND EXPLANATION

Class V — membranous lupus nephritis.

Subepithelial immune deposition and basement-membrane remodeling account for the membranous morphology.

Slide 68 · Case: Extensive global sclerosis

HYPOTHETICAL TEACHING CASE

SLE with longstanding reduction in renal function.

Biopsy: 10 of 11 glomeruli entirely globally sclerosed.

PATTERN AND EXPLANATION

Class VI — advanced sclerosing lupus nephritis.

More than 90% of glomeruli are globally scarred; The dominant lesion is chronic destruction.

Slide 69 · A disciplined classification sequence

Are ≥90% of glomeruli globally sclerosed? → consider class VI

Is there membranous subepithelial capillary-wall disease? → identify class V component

If active proliferation is present: Determine focal versus diffuse glomerular involvement

If mesangial only: Normal LM suggests I; Mesangial proliferation suggests II

Slide 70 · What an immunofluorescence panel does not do

Multiple immune-reactant deposits support immune-complex disease.

Granular distribution helps localize deposits.

The panel alone cannot quantify necrosis, crescents, or sclerosis.

LM and EM remain essential for structural classification.

Diagnostic integration is stronger than any one technique.

Slide 71 · Avoid confusion with other immune glomerulopathies

Consideration

Lupus nephritis

Other immune-complex disease

Systemic context

Established SLE / systemic autoimmunity

Alternative clinical context

Deposits

Frequently IgG ± IgA, IgM, C3, C1q

Composition/distribution vary

Interpretation

Class determined by morphology

Different disease-specific classification

Slide 72 · Morphology-based recall: One feature per class

III

Mesangial deposits; normal LM

Mesangial proliferation

Focal proliferative

Diffuse proliferative

Membranous thickening

Global sclerosis ≥90%

Slide 73 · Five pathology principles to retain

Lupus nephritis is a systemic immune-complex disorder with several renal targets.

Mesangial, subendothelial, and subepithelial deposits lead to different patterns of injury.

Classes III and IV differ primarily in the extent of proliferative glomerular disease.

Class V causes membranous remodeling; Class VI denotes extensive global sclerosis.

Classify the biopsy with LM, IF, and EM while recording extraglomerular pathology.

Slide 74 · Primary reference and scope

Robbins, Cotran & Kumar: Pathologic Basis of Disease. 11th edition (2026).

Lupus nephritis, glomerular immune injury, and systemic lupus pathogenesis sections.

All figures in this lecture are original PowerPoint schematics, not diagnostic specimen images.

Classification is interpreted alongside the full biopsy and clinical findings.