Glomerular Lesions Associated With Systemic Diseases

Slide 1 · Glomerular Lesions Associated

With Systemic Diseases

Lupus nephritis • Henoch–Schönlein purpura

Morphology, immune deposits, and clinicopathologic correlation

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Connect systemic immune diseases with distinct renal morphologic patterns.

Differentiate the six lupus nephritis classes by anatomic distribution and activity.

Explain the IgA-associated clinical and renal spectrum of Henoch–Schönlein purpura.

Interpret clinical syndromes using light microscopy, immunofluorescence, and electron microscopy.

Slide 3 · Systemic diseases can injure the glomerulus

Immunologic, metabolic, and hereditary systemic disorders may produce glomerular injury.

In systemic lupus erythematosus and diabetes, renal involvement may be a major manifestation.

This section focuses on lupus nephritis and Henoch–Schönlein purpura; Other systemic lesions are addressed elsewhere.

Systemic pathways to renal injury

Immune

Lupus immune complexes

Metabolic

Diabetes (elsewhere)

Hereditary

Inherited disorders (elsewhere)

Schematic classification; Not an exhaustive disease list.

Slide 4 · Renal pathology reflects more than one mechanism

Immune complexes may localize in mesangial or capillary-wall compartments.

Inflammatory cellular proliferation, capillary necrosis, and crescents express active injury.

Extrarenal disease does not specify the glomerular lesion without morphologic evaluation.

Immune-complex glomerular injury

Systemic autoimmunity

Glomerular deposits

Inflammatory response

Capillary injury

Causal framework summarized from the described deposits and lesions.

Slide 5 · Clinical presentations span several syndromes

Hematuria may be microscopic or gross and can recur.

Inflammatory glomerular injury may produce nephritic syndrome or rapidly progressive glomerulonephritis.

Nephrotic syndrome, renal insufficiency, and hypertension may coexist with other findings.

Patterns of clinical presentation

Hematuria

Nephritic syndrome

Nephrotic syndrome

RPGN

Hypertension

Renal failure

Clinical syndromes are not a direct substitute for biopsy class.

Slide 6 · Three modalities provide complementary evidence

Light microscopy identifies cellularity, necrosis, crescents, capillary-wall change, and scarring.

Immunofluorescence maps immunoglobulin and complement deposits.

Electron microscopy helps localize immune-complex deposits within glomerular structures.

Complementary tissue modalities

Light microscopy

Cells • matrix • scarring

Immunofluorescence

Immune-reactant distribution

Electron microscopy

Ultrastructural deposits

The modalities answer different morphologic questions.

Slide 7 · Deposit location is a diagnostic clue

Mesangial immune complexes are prominent in early lupus patterns and IgA-associated disease.

Subendothelial deposits contribute to capillary-wall injury and wire-loop appearances in proliferative lupus nephritis.

Subepithelial deposits are characteristic of membranous lupus nephritis.

Where immune complexes accumulate

Capillary lumen

Endothelium

Subendothelial aspect

Glomerular basement membrane

Subepithelial aspect

Podocyte / urinary side

Red dots: Schematic immune deposits

Slide 8 · Glomerular activity and chronicity differ

Proliferation, necrosis, and crescent formation signify active tissue injury.

Global or segmental sclerosis represents scarring after earlier lesions.

A lesion can resolve or evolve to chronic damage; The current biopsy represents one time point.

Active lesions versus outcomes

Necrosis / proliferation

Healing pathway

Recovery OR segmental/global scar

Repair may restore architecture or leave chronic scars.

Slide 9 · Lupus nephritis: A major SLE manifestation

Clinically significant renal involvement in up to 50% of patients with systemic lupus erythematosus.

Glomerulopathy and tubulointerstitial nephritis are important forms of renal disease.

The clinical spectrum extends from asymptomatic urine abnormalities to renal failure.

Patterns of clinical presentation

Hematuria

Nephritic syndrome

Nephrotic syndrome

RPGN

Hypertension

Renal failure

Clinical syndromes are not a direct substitute for biopsy class.

Slide 10 · Immune-complex deposition underlies most lesions

Immune complexes accumulate within glomerular compartments.

Mesangial and glomerular basement membrane deposits are common sites.

The distribution of deposits helps explain the morphologic diversity across classes.

Immune-complex glomerular injury

Systemic autoimmunity

Glomerular deposits

Inflammatory response

Capillary injury

Causal framework summarized from the described deposits and lesions.

Slide 11 · Lupus immunofluorescence involves multiple reactants

IgG is usually detected within lupus glomerular immune complexes.

IgA and IgM may accompany IgG.

C3 and C1q frequently accompany the immunoglobulins and signal complement-associated immune deposition.

Lupus glomerular immune reactants

Often prominent

IgG

May accompany

IgA • IgM

Complement reactants

C3 • C1q

Reactive staining is characteristic; Patterns vary.

Slide 12 · One systemic disease, several renal phenotypes

Renal lupus may manifest with hematuria, nephritic sediment, nephrotic syndrome, or renal insufficiency.

Even within the same biopsy category, clinical severity can vary.

Glomerular, tubulointerstitial, and vascular lesions can occur separately or together.

Renal involvement beyond glomeruli

Glomeruli

Immune complexes / proliferation

Tubules & interstitium

Deposits and inflammation

Vessels

Deposits ± vasculitis / TMA

The same systemic disease may involve multiple compartments.

Slide 13 · Lupus nephritis has six morphologic classes

Classification distinguishes mesangial, proliferative, membranous, and advanced sclerosing patterns.

Lesions may overlap, and the same patient can shift patterns over time.

In the source account, class I is least common and class IV the most common pattern.

The six renal morphologic classes

I

Minimal mesangial

II

Mesangial proliferative

III

Focal

IV

Diffuse

V

Membranous

VI

Advanced sclerosing

Slide 14 · The biopsy classification is not immutable

An initial mesangial pattern can coexist with injury in other renal compartments.

An active proliferative pattern may heal or produce permanent glomerular scars.

Clinical evolution may require reassessment because biopsy class represents sampled tissue at a particular time.

Active lesions versus outcomes

Necrosis / proliferation

Healing pathway

Recovery OR segmental/global scar

Repair may restore architecture or leave chronic scars.

Slide 15 · Class I: Minimal mesangial lupus nephritis

Immune-complex deposits occur within mesangial regions.

Light microscopy shows no structural glomerular abnormalities.

The deposits are demonstrable by immunofluorescence and electron microscopy.

Class I: Deposits without LM change

Mesangial immune complexes

Schematic drawing — not a histologic specimen.

Slide 16 · Class I illustrates a microscopy mismatch

Normal-appearing glomeruli on light microscopy do not exclude immune-complex glomerular disease.

Mesangial deposits may be present without visible mesangial hypercellularity.

Diagnosis depends on integrating complementary diagnostic modalities.

Complementary tissue modalities

Light microscopy

Cells • matrix • scarring

Immunofluorescence

Immune-reactant distribution

Electron microscopy

Ultrastructural deposits

The modalities answer different morphologic questions.

Slide 17 · Class I may have associated non-class lesions

Lupus podocytopathy may resemble minimal change disease.

Tubulointerstitial inflammation can be present despite subtle glomerular changes.

Thrombotic microangiopathy can coexist with otherwise minimal mesangial findings.

Renal involvement beyond glomeruli

Glomeruli

Immune complexes / proliferation

Tubules & interstitium

Deposits and inflammation

Vessels

Deposits ± vasculitis / TMA

The same systemic disease may involve multiple compartments.

Slide 18 · Class II: Mesangial proliferative nephritis

Mesangial cells proliferate; Mesangial matrix accumulation is often present.

Immune complexes and complement show granular mesangial deposits.

Capillary involvement and active endocapillary inflammation are absent in the defining pattern.

Class II: Proliferative mesangium

Mesangial hypercellularity

Schematic drawing — not a histologic specimen.

Slide 19 · Class II deposits remain mesangial

The distribution of immunoglobulins and complement is mesangial.

Increased mesangial cells and matrix distinguish class II from class I on light microscopy.

This pattern should not be confused with the necrotizing or capillary proliferative lesions of classes III and IV.

Class I: Deposits without LM change

Mesangial immune complexes

Schematic drawing — not a histologic specimen.

Slide 20 · Classes I and II: Decisive distinction

Feature

Class I

Class II

Light microscopy

No glomerular structural change

Mesangial hypercellularity ± matrix

IF / EM

Mesangial immune deposits

Mesangial immune deposits

Endocapillary activity

Not defining

Not part of defining pattern

Interpretive point

Deposits may be occult on LM

Proliferation visible on LM

Slide 21 · Class III: Focal lupus nephritis

Fewer than 50% of sampled glomeruli are involved in the source definition.

Affected glomeruli can show segmental or global lesions.

Focal describes how many glomeruli are affected, not how much of any single tuft is injured.

Extent of glomerular involvement

Focal: Class III

Fewer than half of glomeruli involved

< 50%

Bar illustrates the definition, not a case dataset.

Slide 22 · Segmental and global describe lesion extent

A segmental lesion occupies part of an individual glomerular tuft.

A global lesion involves the entire individual glomerulus.

Either can occur within the focal pattern of class III lupus nephritis.

How far a lesion extends within one glomerulus

Segmental

Global

Portion of tuft

Entire tuft

Extensiveness within a glomerulus differs from focal/diffuse.

Slide 23 · Class III: Active inflammatory morphology

Endothelial and mesangial cells may swell or proliferate.

Leukocytes accumulate in affected glomerular capillary loops.

Hyaline thrombi and necrotizing lesions may be present.

Capillary hypercellularity

Endocapillary hypercellularity

Schematic drawing — not a histologic specimen.

Slide 24 · Class III: Necrosis and crescents

Focal capillary necrosis may accompany extracapillary proliferation.

Cellular crescents form in Bowman space near injured capillary loops.

These lesions indicate active glomerular inflammation rather than simple mesangial deposit accumulation.

Extracapillary crescent formation

Cellular crescent at tuft periphery

Schematic drawing — not a histologic specimen.

Slide 25 · Class III: Nephritic urinary sediment

Hematuria and variable proteinuria are common presentations.

Red cell casts correlate with active disease and a nephritic urinary sediment.

Clinical severity ranges from relatively mild urinary abnormalities to acute renal insufficiency.

Patterns of clinical presentation

Hematuria

Nephritic syndrome

Nephrotic syndrome

RPGN

Hypertension

Renal failure

Clinical syndromes are not a direct substitute for biopsy class.

Slide 26 · Class III can heal or become chronic

Inflammatory lesions may regress with restoration of glomerular architecture.

Other lesions heal by segmental or global glomerular scarring.

Some cases progress to diffuse glomerulonephritis, underscoring the changing disease pattern.

Active lesions versus outcomes

Necrosis / proliferation

Healing pathway

Recovery OR segmental/global scar

Repair may restore architecture or leave chronic scars.

Slide 27 · Class IV: Diffuse lupus nephritis

The source describes involvement of more than 50% of glomeruli.

It is the most common and among the most severe morphologic forms.

Inflammatory lesions resemble class III but are more extensive across the biopsy.

Class IV: Diffuse involvement

Diffuse: Class IV

More than half of glomeruli affected (source wording)

> 50%

Illustrative bar; No patient percentages are implied.

Slide 28 · Class IV: Marked cellular proliferation

Endothelial and mesangial proliferation increase glomerular cellularity.

Epithelial proliferation can create prominent extracapillary crescents.

Capillary lumina may be distorted or compromised by the inflammatory response.

Capillary hypercellularity

Endocapillary hypercellularity

Schematic drawing — not a histologic specimen.

Slide 29 · Class IV: Crescents may fill Bowman space

Injured glomeruli may develop extensive epithelial-cell proliferation.

Cellular crescents can occupy the urinary space around the tuft.

Necrosis and active proliferation often occur with other immune-complex-mediated lesions.

Extracapillary crescent formation

Cellular crescent at tuft periphery

Schematic drawing — not a histologic specimen.

Slide 30 · Wire loops indicate subendothelial deposits

Extensive subendothelial immune complexes thicken capillary walls.

Circumferential wall thickening creates the light-microscopic “wire loop” appearance.

The morphologic observation is supported by electron-dense deposits on ultrastructural examination.

Subendothelial deposits

Capillary lumen

Endothelium

Subendothelial aspect

Glomerular basement membrane

Subepithelial aspect

Podocyte / urinary side

Red dots: Schematic immune deposits

Slide 31 · The subendothelial position is mechanistic

Subendothelial deposits lie between endothelium and glomerular basement membrane.

Immune complexes at this interface accompany capillary-wall inflammatory changes.

Their abundant accumulation distinguishes the classic wire-loop lesion from a purely mesangial process.

Subendothelial deposits

Capillary lumen

Endothelium

Subendothelial aspect

Glomerular basement membrane

Subepithelial aspect

Podocyte / urinary side

Red dots: Schematic immune deposits

Slide 32 · Class IV: Immunofluorescence and EM correlate

Immune-complex deposition is readily demonstrable by immunofluorescence.

Electron microscopy identifies electron-dense deposits within involved capillary walls.

Correlating stain distribution with the light-microscopic lesion strengthens interpretation.

Complementary tissue modalities

Light microscopy

Cells • matrix • scarring

Immunofluorescence

Immune-reactant distribution

Electron microscopy

Ultrastructural deposits

The modalities answer different morphologic questions.

Slide 33 · Class IV commonly produces symptomatic renal disease

Patients generally have hematuria together with proteinuria.

Hypertension may accompany extensive glomerular inflammation.

Renal insufficiency may range from mild impairment to severe dysfunction.

Patterns of clinical presentation

Hematuria

Nephritic syndrome

Nephrotic syndrome

RPGN

Hypertension

Renal failure

Clinical syndromes are not a direct substitute for biopsy class.

Slide 34 · Classes III and IV differ chiefly in extent

Comparison

Class III — focal

Class IV — diffuse

Glomerular distribution

Fewer than 50% involved

More than 50% involved (source)

Inflammatory pattern

Segmental or global active lesions

Similar lesions, more extensive

Necrosis / crescents

May be present

May be prominent

Clinical spectrum

Mild urine findings → AKI

Common hematuria / proteinuria; Renal insufficiency

Long-term lesion

May scar or progress

May progress to glomerulosclerosis

Slide 35 · Class V: Membranous lupus nephritis

Diffuse capillary-wall thickening is the principal light-microscopic feature.

The thickening reflects subepithelial immune-complex deposits.

Basement membrane–like material accumulates around the deposits.

Subepithelial deposits

Capillary lumen

Endothelium

Subendothelial aspect

Glomerular basement membrane

Subepithelial aspect

Podocyte / urinary side

Red dots: Schematic immune deposits

Slide 36 · Subepithelial deposits alter the filtration wall

The deposits lie external to the glomerular basement membrane beneath podocytes.

Capillary walls become diffusely thickened as additional basement membrane material is produced.

The pattern parallels primary membranous nephropathy morphologically.

Capillary-wall compartments

Capillary lumen

Endothelium

Subendothelial aspect

Glomerular basement membrane

Subepithelial aspect

Podocyte / urinary side

Slide 37 · Class V commonly presents with nephrosis

Severe proteinuria or nephrotic syndrome is a typical clinical presentation.

The lesion emphasizes filtration-barrier injury rather than obligatory florid endocapillary proliferation.

Mesangial immune-complex deposits are also frequently seen.

Site of deposits shapes injury

III–IV

Subendothelial

Proliferative injury

V

Subepithelial

Proteinuria / nephrosis

Simplified clinicopathologic mapping.

Slide 38 · Class V may coexist with proliferative lesions

Membranous lupus nephritis can occur together with focal lupus nephritis.

It can also coexist with diffuse proliferative lupus nephritis.

Interpret the full biopsy; One deposit compartment need not exclude another lesion pattern.

Where immune complexes accumulate

Capillary lumen

Endothelium

Subendothelial aspect

Glomerular basement membrane

Subepithelial aspect

Podocyte / urinary side

Red dots: Schematic immune deposits

Slide 39 · Class VI: Advanced sclerosing lupus nephritis

The defining finding is global sclerosis in 90% or more of glomeruli.

This is a predominantly chronic, scarred morphologic pattern.

It should be distinguished from the active inflammatory findings of proliferative classes.

Class VI is defined by scar burden

≥90% global glomerular sclerosis

Schematic: One glomerulus, not a quantified biopsy.

Slide 40 · Activity and sclerosis answer different questions

Necrosis and crescents represent active injury detectable on microscopy.

Global sclerosis reflects replacement of functioning glomerular architecture by scar.

Severe chronic sclerosis may persist after earlier immune-mediated inflammation has subsided.

Active lesions versus outcomes

Necrosis / proliferation

Healing pathway

Recovery OR segmental/global scar

Repair may restore architecture or leave chronic scars.

Slide 41 · Classes I–VI: Morphology in one comparison

Class

Principal morphology

Key deposit/location clue

I

No LM structural change

Mesangial IF/EM deposits

II

Mesangial cell/matrix increase

Mesangial deposits

III

Focal active ± necrotizing lesions

Variable immune complexes

IV

Diffuse proliferative ± wire loops

Frequent subendothelial deposits

V

Diffuse capillary-wall thickening

Subepithelial deposits

VI

≥90% global sclerosis

Advanced chronic scar

Slide 42 · Renal lupus is not restricted to the glomerulus

Tubular and interstitial changes are frequent in lupus nephritis.

In occasional patients, tubulointerstitial injury dominates the renal abnormalities.

Immune deposits may involve tubular or peritubular capillary basement membranes.

Renal involvement beyond glomeruli

Glomeruli

Immune complexes / proliferation

Tubules & interstitium

Deposits and inflammation

Vessels

Deposits ± vasculitis / TMA

The same systemic disease may involve multiple compartments.

Slide 43 · Interstitial inflammation may be organized

Lupus kidneys sometimes contain well-formed interstitial B-cell follicles.

Plasma cells may accompany the follicles.

The source notes that some interstitial plasma cells may produce autoantibodies locally.

Renal involvement beyond glomeruli

Glomeruli

Immune complexes / proliferation

Tubules & interstitium

Deposits and inflammation

Vessels

Deposits ± vasculitis / TMA

The same systemic disease may involve multiple compartments.

Slide 44 · Vascular immune deposits may accompany lupus

Immune-complex deposits may occur in the intima and media of renal arteries.

Vascular pathology can coexist with glomerular and tubulointerstitial disease.

Active vasculitis is less frequent than mere vascular immune deposition.

Renal involvement beyond glomeruli

Glomeruli

Immune complexes / proliferation

Tubules & interstitium

Deposits and inflammation

Vessels

Deposits ± vasculitis / TMA

The same systemic disease may involve multiple compartments.

Slide 45 · Vasculitis and thrombotic microangiopathy differ

Occasionally, vascular inflammation includes necrosis of the vessel wall.

Thrombotic microangiopathy can coexist with lupus-associated renal disease.

Distinguish these vascular findings from proliferative glomerular lesions in tissue interpretation.

Renal involvement beyond glomeruli

Glomeruli

Immune complexes / proliferation

Tubules & interstitium

Deposits and inflammation

Vessels

Deposits ± vasculitis / TMA

The same systemic disease may involve multiple compartments.

Slide 46 · Evaluate the entire renal biopsy

Count the distribution of involved glomeruli and describe segmental or global lesions.

Identify necrosis, crescents, capillary-wall thickening, and chronic scarring.

Examine the tubulointerstitium and vessels in addition to glomerular deposits.

Pathology interpretation sequence

Distribution

Focal versus diffuse

Compartment

Mesangial vs capillary wall

Activity

Necrosis / crescents

Chronicity

Glomerular sclerosis

Slide 47 · Renal syndrome does not determine lupus class

Hematuria and renal insufficiency may be seen in several active classes.

Marked proteinuria commonly accompanies class V, but membranous and proliferative lesions may coexist.

Tissue evidence reconciles the clinical presentation with the underlying injury.

Patterns of clinical presentation

Hematuria

Nephritic syndrome

Nephrotic syndrome

RPGN

Hypertension

Renal failure

Clinical syndromes are not a direct substitute for biopsy class.

Slide 48 · Applied case: Focal proliferative lupus

A patient with SLE develops hematuria, red cell casts, and proteinuria.

Biopsy shows necrosis and crescents in fewer than half of glomeruli.

Question: Which lupus nephritis class best fits the distribution and injury pattern?

Extent of glomerular involvement

Focal: Class III

Fewer than half of glomeruli involved

< 50%

Bar illustrates the definition, not a case dataset.

Slide 49 · Case interpretation: Class III

Fewer than half of glomeruli affected is the defining focal distribution.

Necrotizing capillary injury with crescents supports active proliferative nephritis.

Red cell casts are compatible with a nephritic sediment during active disease.

Extracapillary crescent formation

Cellular crescent at tuft periphery

Schematic drawing — not a histologic specimen.

Slide 50 · Applied case: Thickened glomerular loops

A patient with SLE has substantial proteinuria.

Biopsy shows diffuse capillary-wall thickening and subepithelial immune deposits.

Question: Which lupus class explains these structural findings?

Subepithelial deposits

Capillary lumen

Endothelium

Subendothelial aspect

Glomerular basement membrane

Subepithelial aspect

Podocyte / urinary side

Red dots: Schematic immune deposits

Slide 51 · Case interpretation: Class V

Diffuse capillary-wall thickening with subepithelial immune complexes characterizes class V.

Severe proteinuria and nephrotic syndrome are typical clinical consequences.

Assess separately for concurrent focal or diffuse proliferative lupus nephritis.

Site of deposits shapes injury

III–IV

Subendothelial

Proliferative injury

V

Subepithelial

Proteinuria / nephrosis

Simplified clinicopathologic mapping.

Slide 52 · Henoch–Schönlein purpura: A systemic syndrome

The source describes a childhood-predominant vasculitic syndrome with skin, intestinal, joint, and renal manifestations.

Purpuric skin lesions are accompanied by abdominal symptoms and arthralgias.

Glomerular injury is associated with IgA-containing deposits.

Systemic clinical pattern

Skin

Purpuric lesions

Gut

Pain • bleeding

Joints

Arthralgia

Kidney

Hematuria ± syndrome

The four-organ pattern supports the systemic diagnosis.

Slide 53 · Age distribution influences clinical severity

The syndrome is particularly common in children aged 3–8 years.

Adults may also develop the disease.

Renal manifestations tend to be more severe in adults than in children.

Age modifies the renal presentation

Children (often 3–8 years)

Adults (less frequent)

Renal disease usually more severe in adults

Slide 54 · Clinical onset may follow respiratory infection

The source notes that onset often follows an upper respiratory infection.

Approximately one-third of patients have a background of atopy.

These associations provide context but are not sufficient to establish renal histologic severity.

Systemic clinical pattern

Skin

Purpuric lesions

Gut

Pain • bleeding

Joints

Arthralgia

Kidney

Hematuria ± syndrome

The four-organ pattern supports the systemic diagnosis.

Slide 55 · Purpura has a characteristic distribution

Purpuric lesions often involve extensor surfaces of the arms and legs.

Buttocks are another characteristic site.

Skin biopsy may reveal small-vessel necrotizing vasculitis and subepidermal hemorrhage.

Small-vessel injury in the skin

IgA ± IgG/C3 in dermal vessels

Simplified vascular diagram; Not a skin section.

Slide 56 · Gastrointestinal symptoms are integral

Abdominal pain is common and may be accompanied by vomiting.

Intestinal bleeding can occur as part of systemic vascular involvement.

The presence of gastrointestinal involvement helps distinguish a systemic syndrome from isolated renal disease.

Systemic clinical pattern

Skin

Purpuric lesions

Gut

Pain • bleeding

Joints

Arthralgia

Kidney

Hematuria ± syndrome

The four-organ pattern supports the systemic diagnosis.

Slide 57 · Arthralgia reinforces the multisystem pattern

Joint symptoms occur alongside skin and abdominal manifestations.

The combination of purpura, abdominal symptoms, arthralgia, and renal findings is diagnostically informative.

Systemic involvement should be considered when interpreting IgA-associated glomerular disease.

Systemic clinical pattern

Skin

Purpuric lesions

Gut

Pain • bleeding

Joints

Arthralgia

Kidney

Hematuria ± syndrome

The four-organ pattern supports the systemic diagnosis.

Slide 58 · Renal disease affects about one-third

Renal manifestations in approximately one-third of patients.

Gross or microscopic hematuria is a common renal sign.

Nephritic or nephrotic syndrome may occur, including mixed clinical presentations.

Patterns of clinical presentation

Hematuria

Nephritic syndrome

Nephrotic syndrome

RPGN

Hypertension

Renal failure

Clinical syndromes are not a direct substitute for biopsy class.

Slide 59 · HSP glomerular morphology is heterogeneous

Mild focal mesangial proliferation may be the only finding.

Some biopsies show diffuse mesangial or endocapillary proliferation.

The severe end includes crescentic glomerulonephritis.

Glomerular injury spectrum

Mesangial proliferation

Endocapillary proliferation

Crescentic GN

Range of observed morphologies; Not inevitable progression.

Slide 60 · Mesangial IgA is the defining IF clue

IgA deposits are found in the mesangial regions on immunofluorescence.

IgG and C3 may accompany IgA.

Deposits can sometimes extend from mesangial areas to capillary loops.

IgA-associated mesangial pattern

Mesangial IgA deposits

Schematic drawing — not a histologic specimen.

Slide 61 · The skin and glomerulus share immune deposits

Dermal small vessels show necrotizing vasculitis with subepidermal hemorrhage.

IgA, sometimes with IgG and C3, is demonstrable in involved vessels.

These deposits support an immunologically mediated multisystem vascular process.

Small-vessel injury in the skin

IgA ± IgG/C3 in dermal vessels

Simplified vascular diagram; Not a skin section.

Slide 62 · IgA nephropathy and HSP are closely related

Both conditions show a mesangial distribution of IgA deposits.

The source considers them manifestations of a closely related disease process.

The systemic skin, gastrointestinal, and joint findings distinguish the purpura syndrome clinically.

Immunofluorescence patterns

Lupus nephritis

IgG; Often also IgA, IgM, C3, C1q

Henoch–Schönlein purpura

Mesangial IgA ± IgG/C3

Slide 63 · Crescents can signal a severe renal variant

A small subset develops rapidly progressive glomerulonephritis with numerous crescents.

Severe crescentic disease is described particularly in adults.

This lesion is more concerning than a mild isolated mesangial proliferation.

Extracapillary crescent formation

Cellular crescent at tuft periphery

Schematic drawing — not a histologic specimen.

Slide 64 · Extra-renal vasculitis is usually more conspicuous

Small-vessel vasculitis characterizes cutaneous lesions.

The gastrointestinal tract may also have vasculitic injury.

Vasculitis is relatively uncommon within the kidney itself.

Small-vessel injury in the skin

IgA ± IgG/C3 in dermal vessels

Simplified vascular diagram; Not a skin section.

Slide 65 · The course and prognosis vary

Hematuria may recur over many years following onset.

Most children have an excellent overall prognosis.

Diffuse glomerular lesions, crescents, or nephrotic syndrome are associated with less favorable renal outcomes.

Morphology associated with poorer course

Diffuse renal involvement

Crescents

Nephrotic syndrome

Risk associations as described; No numeric score is implied.

Slide 66 · Lupus nephritis versus Henoch–Schönlein purpura

Feature

Lupus nephritis

Henoch–Schönlein purpura

Systemic setting

SLE

Purpura + gut + joint manifestations

Immune pattern

IgG often with IgA/IgM, C3, C1q

Mesangial IgA ± IgG/C3

Morphologic range

Six lupus classes

Mesangial → proliferative → crescentic

Associated disease

Tubulointerstitial and vascular lesions

Dermal small-vessel vasculitis

Clinical concern

Activity, extent, scarring

Adult severity and crescents

Slide 67 · Applied case: Multisystem IgA-associated disease

A child develops purpura on the legs and buttocks, abdominal pain, and hematuria.

Renal biopsy shows mesangial proliferation and predominant mesangial IgA deposits.

Question: What syndrome best unifies the extrarenal and renal manifestations?

Systemic clinical pattern

Skin

Purpuric lesions

Gut

Pain • bleeding

Joints

Arthralgia

Kidney

Hematuria ± syndrome

The four-organ pattern supports the systemic diagnosis.

Slide 68 · Case interpretation: Henoch–Schönlein purpura

Purpura with abdominal symptoms and hematuria supports the systemic syndrome.

Mesangial IgA staining closely links the renal lesion with IgA-associated nephropathy.

Renal severity still depends on the observed injury pattern, especially diffuse proliferation or crescents.

IgA-associated mesangial pattern

Mesangial IgA deposits

Schematic drawing — not a histologic specimen.

Slide 69 · The crucial tissue discriminators

Deposit predominance: Lupus often has IgG with several other reactants; HSP has mesangial IgA.

Distribution: Mesangial versus capillary wall and focal versus diffuse.

Injury state: Active necrosis/proliferation versus established sclerosis.

Immunofluorescence patterns

Lupus nephritis

IgG; Often also IgA, IgM, C3, C1q

Henoch–Schönlein purpura

Mesangial IgA ± IgG/C3

Slide 70 · Integrated pathology checklist

Identify the systemic syndrome and renal clinical manifestations.

Use LM to describe cell proliferation, crescents, necrosis, membrane thickening, and scarring.

Use IF and EM to map immune deposits and integrate extraglomerular lesions.

Pathology interpretation sequence

Distribution

Focal versus diffuse

Compartment

Mesangial vs capillary wall

Activity

Necrosis / crescents

Chronicity

Glomerular sclerosis

Slide 71 · Core concepts to retain

Systemic lupus erythematosus produces diverse renal immune-complex lesions, formally described in six classes.

Deposit localization, extent, and inflammatory activity explain key patterns of clinical presentation.

Henoch–Schönlein purpura links a systemic vasculitic syndrome to predominant mesangial IgA deposition.

Immune-complex glomerular injury

Systemic autoimmunity

Glomerular deposits

Inflammatory response

Capillary injury

Causal framework summarized from the described deposits and lesions.

Slide 72 · Reference and scope

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

Primary teaching section: Glomerular Lesions Associated With Systemic Diseases, including lupus nephritis and Henoch–Schönlein purpura.

The textbook figure series depicts proliferative lesions, wire loops, ultrastructural deposits, and granular IgG staining.