Medicine – Glomerulonephritis

Glomerulonephritis (GN) refers to a group of disorders in which the renal glomeruli become inflamed or structurally damaged, leading to abnormalities of glomerular filtration.

Depending on the underlying disease, glomerular injury can produce haematuria, proteinuria, reduced glomerular filtration rate, hypertension, oedema, nephritic syndrome, nephrotic syndrome, or rapidly progressive kidney failure.

1. What Is the Glomerulus?

The glomerulus is a specialised capillary network responsible for filtering blood and producing the initial ultrafiltrate that eventually becomes urine.

The normal glomerular filtration barrier consists mainly of:

Fenestrated glomerular endothelial cells.

Glomerular basement membrane – GBM.

Podocytes with filtration slit diaphragms.

Damage to any of these structures can disturb filtration.

2. Definition of Glomerulonephritis

Glomerulonephritis describes:

Inflammatory or immune-mediated injury involving the glomeruli.

This can cause both:

Structural changes

and

Functional changes.

Not every glomerular disease is strongly inflammatory, however. For example, minimal change disease and focal segmental glomerulosclerosis are usually classified as glomerular diseases rather than classic inflammatory nephritides.

3. Structural Changes

Possible structural changes within diseased glomeruli include:

Glomerular cellular proliferation.

Infiltration by inflammatory leukocytes.

Mesangial proliferation.

Capillary-wall thickening.

Glomerular basement membrane abnormalities.

Immune-complex deposition.

Glomerular sclerosis.

Crescent formation in severe disease.

The exact pattern depends on the specific disease.

4. Cellular Proliferation

Glomerular inflammation may stimulate proliferation of:

Mesangial cells.

Endothelial cells.

Parietal epithelial cells.

In rapidly progressive glomerulonephritis, proliferation of parietal epithelial cells within Bowman’s space contributes to:

Crescent formation.

5. Leukocyte Infiltration

Inflammatory glomerular disorders may contain:

Neutrophils.

Monocytes.

Other inflammatory cells.

This is particularly prominent in some forms of:

Post-infectious glomerulonephritis.

6. Basement Membrane Changes

The GBM may become abnormal because of:

Immune deposits.

Antibody binding.

Structural thickening.

Splitting or duplication.

Examples include:

Membranous nephropathy → capillary-wall thickening with subepithelial immune deposits.

Membranoproliferative GN → duplicated or “double-contour” capillary walls.

Anti-GBM disease → antibody binding directly along the GBM.

7. Functional Changes

The most important functional abnormalities include:

Proteinuria.

Haematuria.

Reduced GFR.

Additional consequences may include:

Salt and water retention.

Oedema.

Hypertension.

Acute kidney injury.

8. Proteinuria

Proteinuria occurs when the glomerular filtration barrier becomes abnormally permeable to plasma proteins, particularly:

Albumin.

Severe protein loss can produce:

Nephrotic syndrome.

9. Haematuria

Damage to glomerular capillaries allows red blood cells to enter the urine.

Glomerular haematuria may produce:

Dysmorphic red blood cells

and

Red blood cell casts.

These strongly support a glomerular source of bleeding.

10. Reduced GFR

Inflammation, capillary obstruction, glomerular injury, or sclerosis can reduce:

Glomerular filtration rate.

The result may be:

Acute kidney injury

or, if progressive and irreversible:

Chronic kidney disease.

11. Nephritic Syndrome

A predominantly inflammatory glomerular lesion often presents as:

Nephritic syndrome.

Typical features include:

Haematuria.

RBC casts.

Proteinuria, usually less severe than nephrotic-range.

Reduced GFR.

Oliguria.

Hypertension.

Oedema.

12. Nephrotic Syndrome

A predominantly permeability-related glomerular disorder may produce:

Nephrotic syndrome.

The major features are:

Heavy proteinuria.

Hypoalbuminaemia.

Generalised oedema.

Hyperlipidaemia.

Lipiduria.

13. Major Patterns of Glomerular Disease

Important glomerular diseases include:

Minimal change disease.

Membranous nephropathy.

Focal segmental glomerulosclerosis.

IgA nephropathy.

Membranoproliferative glomerulonephritis.

Post-infectious proliferative glomerulonephritis.

Rapidly progressive crescentic glomerulonephritis.

14. Minimal Change Disease

Minimal change disease (MCD) is a glomerular disorder that classically causes:

Nephrotic syndrome.

It is particularly important in:

Children.

15. Minimal Change Disease – Epidemiology

The original note states:

“Most common.”

This needs qualification.

Minimal change disease is:

The most common cause of nephrotic syndrome in children.

It is not simply the most common type of all glomerulonephritis.

16. Minimal Change Disease – Light Microscopy

On ordinary light microscopy, the glomeruli usually appear:

Normal or nearly normal.

This explains the name:

Minimal change disease.

17. Minimal Change Disease – Electron Microscopy

Electron microscopy demonstrates:

Diffuse effacement of podocyte foot processes.

Older notes sometimes call this:

“Fusion of epithelial foot processes.”

The more accurate modern term is:

Foot-process effacement.

18. Minimal Change Disease – Immunofluorescence

Immunofluorescence is usually:

Negative or essentially normal.

This helps distinguish minimal change disease from immune-complex glomerulonephritides.

19. Minimal Change Disease – Clinical Features

Patients typically present with:

Sudden nephrotic syndrome.

Features include:

Heavy proteinuria.

Hypoalbuminaemia.

Oedema.

Renal function is often preserved, particularly in children.

20. Minimal Change Disease – Associations

Most childhood cases are idiopathic.

Possible secondary associations include:

NSAIDs.

Hodgkin lymphoma.

Some allergic or immune conditions.

21. Minimal Change Disease – Treatment

Minimal change disease is highly responsive to:

Corticosteroids.

This is especially true in children.

Therefore, rather than saying:

“Some require steroids,”

it is more accurate to say:

Corticosteroids are a major treatment, with most children showing a good response.

22. Minimal Change Disease – Prognosis

The prognosis is generally:

Excellent.

Relapses may occur, but progression to severe chronic kidney disease is uncommon in typical childhood steroid-responsive disease.

23. Minimal Change Disease – Key Pattern

Remember:

CHILD + NEPHROTIC SYNDROME + NORMAL LIGHT MICROSCOPY + PODOCYTE FOOT-PROCESS EFFACEMENT → MINIMAL CHANGE DISEASE.

24. Membranous Nephropathy

Membranous nephropathy is an important cause of:

Nephrotic syndrome in adults.

It results from immune deposits along the outer, or subepithelial, aspect of the glomerular capillary wall.

25. Membranous Nephropathy – Presentation

Patients may present with:

Nephrotic syndrome.

Heavy proteinuria without full nephrotic syndrome.

Progressive CKD in some cases.

The older term:

CRF

should be replaced with:

Chronic kidney disease – CKD.

26. Membranous Nephropathy – Pathology

The characteristic lesion is:

Diffuse thickening of glomerular capillary walls.

Immune deposits occur in a:

Subepithelial location.

27. Immune Deposits in Membranous Nephropathy

The deposits commonly contain:

IgG

and

Complement, particularly C3.

On immunofluorescence there is usually:

Granular IgG and C3 deposition along the capillary walls.

28. Membranous Nephropathy – Electron Microscopy

Electron microscopy demonstrates:

Subepithelial electron-dense deposits.

The GBM grows between the deposits, producing the classic:

“Spike and dome” appearance.

29. Primary Membranous Nephropathy

Many primary cases are caused by antibodies against podocyte antigens, most importantly:

PLA2R – phospholipase A2 receptor.

Another recognised antigen is:

THSD7A.

30. Secondary Membranous Nephropathy

Secondary causes include:

SLE.

Hepatitis B.

Some malignancies.

Certain drugs.

Therefore, secondary causes should be considered according to the patient’s age and clinical context.

31. Membranous Nephropathy – Complications

Patients with nephrotic syndrome have an increased risk of:

Venous thromboembolism.

Membranous nephropathy is particularly associated with:

Renal vein thrombosis.

32. Membranous Nephropathy – Key Pattern

Remember:

ADULT + NEPHROTIC SYNDROME + THICK GBM + SUBEPITHELIAL IgG/C3 DEPOSITS → MEMBRANOUS NEPHROPATHY.

33. Focal Segmental Glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is characterised by scarring of selected portions of selected glomeruli.

The name describes the pathology:

Focal = only some glomeruli affected.

Segmental = only part of an affected glomerulus is scarred.

Glomerulosclerosis = scarring of the glomerulus.

34. FSGS – Presentation

Patients commonly present with:

Proteinuria.

Nephrotic syndrome.

Hypertension.

Some patients also develop:

Progressive reduction in renal function.

35. Primary and Secondary FSGS

FSGS may be:

Primary.

or

Secondary.

Secondary causes include adaptive glomerular stress or injury.

36. FSGS – Important Associations

Associations include:

HIV infection.

Obesity.

Reduced nephron mass.

Sickle cell disease.

Some drugs.

Genetic podocyte disorders.

37. FSGS – Pathology

Light microscopy shows:

Segmental areas of sclerosis and hyalinosis in some glomeruli.

Electron microscopy often demonstrates:

Podocyte foot-process effacement.

38. FSGS – Prognosis

FSGS is generally less steroid-responsive than minimal change disease and has a greater risk of progression to:

Chronic kidney disease

and

ESKD.

39. FSGS – Key Pattern

Remember:

FOCAL + SEGMENTAL SCARRING + PROTEINURIA/NEPHROTIC SYNDROME → FSGS.

40. IgA Nephropathy

IgA nephropathy, also known as:

Berger disease,

is an immune-mediated glomerular disorder characterised by deposition of:

IgA within the glomerular mesangium.

It is one of the most common primary glomerular diseases worldwide.

41. IgA Nephropathy – Age

IgA nephropathy commonly affects:

Children, adolescents, and young adults,

although it may occur at any age.

42. IgA Nephropathy – Classic Presentation

The classic presentation is:

Visible haematuria occurring during or shortly after an upper respiratory tract infection.

This is sometimes called:

Synpharyngitic haematuria.

43. Timing after Pharyngitis

A very important distinction is that IgA nephropathy typically causes haematuria:

At the same time as, or within a few days of, a respiratory infection.

This differs from post-streptococcal glomerulonephritis, which usually occurs after a latent interval.

44. IgA Nephropathy – Other Presentations

Patients may also have:

Persistent microscopic haematuria.

Proteinuria.

Hypertension.

Progressive CKD.

Some develop nephritic syndrome.

45. IgA Nephropathy – Pathology

Light microscopy often demonstrates:

Mesangial proliferation.

Immunofluorescence demonstrates:

Mesangial IgA deposition.

C3 may also be present.

46. IgA Nephropathy – Prognosis

The course is highly variable.

Some patients have mild disease for decades, while others develop:

Progressive CKD and ESKD.

Risk factors for progression include:

Persistent proteinuria.

Hypertension.

Reduced GFR.

Significant chronic changes on biopsy.

47. IgA Nephropathy – Key Pattern

Remember:

YOUNG PERSON + HAEMATURIA DURING/IMMEDIATELY AFTER PHARYNGITIS + MESANGIAL IgA → IgA NEPHROPATHY.

48. Membranoproliferative Glomerulonephritis

The older term:

Mesangiocapillary glomerulonephritis

is commonly replaced by:

Membranoproliferative glomerulonephritis – MPGN.

MPGN describes a characteristic pattern of glomerular injury rather than a single disease.

49. MPGN – Presentation

Patients may present with:

Nephritic syndrome.

Nephrotic syndrome.

Mixed nephritic-nephrotic features.

Proteinuria.

Haematuria.

Hypertension.

Reduced renal function.

50. MPGN – Pathology

There is typically:

Mesangial proliferation.

Endocapillary proliferation.

Capillary-wall remodelling.

The GBM may show:

Duplication or splitting.

This produces the classic:

Double-contour or “tram-track” appearance.

51. Why the Double Contour Occurs

The double contour results from:

New basement membrane formation around deposits and interposed mesangial cells.

This gives the capillary wall a duplicated appearance on microscopy.

52. Modern Classification of MPGN

Older classifications divided MPGN into:

Type I.

Type II.

Type III.

Modern classification focuses more on the underlying mechanism:

Immune-complex-mediated MPGN.

or

Complement-mediated disease / C3 glomerulopathy.

53. C3 Nephritic Factor

The original note states:

“60% have C3 nephritic factor.”

This should not be applied to all MPGN.

C3 nephritic factor is particularly associated with abnormalities of the alternative complement pathway, especially:

C3 glomerulopathy

including the disorder historically known as:

Dense deposit disease.

54. Complement in MPGN

Complement levels may be:

Low,

especially in complement-mediated forms and some immune-complex forms.

Therefore, hypocomplementaemia is an important diagnostic clue.

55. Causes of Immune-Complex MPGN

Possible causes include:

Chronic infections.

Hepatitis B.

Hepatitis C.

Autoimmune disease.

Monoclonal immunoglobulin disorders.

56. MPGN – Key Pattern

Remember:

NEPHRITIC + NEPHROTIC FEATURES + LOW COMPLEMENT + DOUBLE-CONTOUR/TRAM-TRACK GBM → THINK MPGN.

57. Post-Infectious Glomerulonephritis

The older term:

Diffuse proliferative glomerulonephritis

may describe the histological pattern seen in:

Post-infectious glomerulonephritis.

Classically this follows infection with certain strains of:

Group A Streptococcus.

58. Post-Streptococcal Glomerulonephritis

Post-streptococcal glomerulonephritis, or:

PSGN,

typically develops after:

Streptococcal pharyngitis

or

Streptococcal skin infection.

59. Timing after Infection

Unlike IgA nephropathy, PSGN occurs after a:

Latent interval.

Classically:

About 1–3 weeks after pharyngitis.

The interval after skin infection may be somewhat longer.

60. PSGN – Typical Age

PSGN is particularly common in:

Children.

However, adults can also develop it and may experience more severe disease.

61. PSGN – Presentation

The typical presentation is:

Acute nephritic syndrome.

Features include:

Tea- or cola-coloured urine.

Haematuria.

Oedema.

Hypertension.

Reduced urine output.

AKI.

Mild-to-moderate proteinuria.

62. Complement in PSGN

A classic laboratory finding is:

Low serum C3.

Complement usually returns toward normal over several weeks.

Persistent low complement should prompt consideration of an alternative diagnosis.

63. Evidence of Recent Streptococcal Infection

Tests may include:

ASO titre – antistreptolysin O.

However, after streptococcal skin infection, ASO may be less reliable.

Another useful antibody is:

Anti-DNase B.

64. PSGN – Light Microscopy

Light microscopy typically shows:

Diffuse endocapillary hypercellularity.

There may be numerous:

Neutrophils.

This produces a proliferative glomerulonephritis.

65. PSGN – Immunofluorescence

Immunofluorescence typically shows:

Granular IgG and C3 deposition.

This is often described as:

“Lumpy-bumpy” staining.

66. PSGN – Electron Microscopy

Electron microscopy classically demonstrates:

Subepithelial immune-complex deposits.

These are known as:

Subepithelial humps.

67. PSGN – Prognosis

Children usually have an:

Excellent prognosis.

Adults generally have a greater risk of:

Persistent renal impairment.

Treatment is mainly supportive, including management of:

Fluid overload.

Hypertension.

Electrolyte abnormalities.

68. PSGN – Key Pattern

Remember:

CHILD + NEPHRITIC SYNDROME 1–3 WEEKS AFTER STREP THROAT + LOW C3 → PSGN.

69. IgA Nephropathy versus PSGN – Note Form

IgA nephropathy:

Haematuria occurs during or immediately after respiratory infection.

Mesangial IgA deposition.

Complement usually normal.

Post-streptococcal GN:

Haematuria usually occurs after a latent interval.

Often 1–3 weeks after pharyngitis.

Low C3.

Granular IgG/C3.

Subepithelial humps.

70. Rapidly Progressive Glomerulonephritis

Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome characterised by:

Rapid deterioration of renal function over days to weeks, sometimes extending over several months,

together with:

Crescent formation in the glomeruli.

It is therefore also called:

Crescentic glomerulonephritis.

71. Clinical Features of RPGN

Patients typically have:

Haematuria.

Proteinuria.

RBC casts.

Rapidly rising creatinine.

Reduced urine output.

Hypertension.

Without treatment, severe disease may progress rapidly to:

ESKD.

72. Crescent Formation

Crescents form in:

Bowman’s space

when severe glomerular capillary-wall injury allows:

Fibrin and inflammatory mediators

to enter the urinary space.

This stimulates proliferation of:

Parietal epithelial cells

and recruitment of inflammatory cells.

73. RPGN Type I – Anti-GBM Disease

Type I RPGN is caused by:

Anti-GBM antibodies.

The classic disease is:

Goodpasture / anti-GBM disease.

Immunofluorescence shows:

Linear IgG deposition along the GBM.

Pulmonary haemorrhage may occur.

74. RPGN Type II – Immune-Complex Disease

Type II RPGN results from:

Immune-complex deposition.

Causes include:

SLE / lupus nephritis.

Post-infectious GN.

IgA nephropathy.

Other immune-complex diseases may also produce severe crescentic disease.

Immunofluorescence is usually:

Granular.

75. RPGN Type III – Pauci-Immune Disease

Type III RPGN is usually caused by:

ANCA-associated vasculitis.

Examples include:

Granulomatosis with polyangiitis – GPA, formerly Wegener granulomatosis.

Microscopic polyangiitis.

Eosinophilic granulomatosis with polyangiitis in selected cases.

76. Pauci-Immune Meaning

Pauci-immune means:

Little or no immune deposition is seen on immunofluorescence.

This is typical of:

ANCA-associated crescentic GN.

77. RPGN – Investigation

Important investigations include:

Urinalysis.

Urine microscopy.

Creatinine and eGFR.

Anti-GBM antibodies.

ANCA.

ANA and anti-dsDNA.

Complement levels.

Infection studies where appropriate.

A:

Renal biopsy

is usually central to establishing the exact type.

78. RPGN – Treatment

RPGN is a:

Nephrological emergency.

Treatment depends on the cause but may involve:

High-dose corticosteroids.

Cyclophosphamide or rituximab.

Plasma exchange in selected anti-GBM disease and certain other specific situations.

Treatment of underlying infection where relevant.

79. Dialysis in RPGN

Severe AKI may require:

Temporary or long-term dialysis.

However, early recognition and treatment can sometimes preserve significant renal function.

80. Kidney Transplantation

Some patients who develop irreversible ESKD may eventually require:

Kidney transplantation.

Transplant timing depends on the underlying disease being appropriately controlled.

81. Prognosis of RPGN

Prognosis depends strongly on:

Renal function at presentation.

Severity of crescent formation.

Degree of chronic scarring.

Underlying cause.

Speed of treatment.

Patients presenting with very advanced, dialysis-dependent disease generally have a lower chance of renal recovery.

82. Major Glomerular Disorders – Note Form

Minimal change disease:

Most common cause of childhood nephrotic syndrome.

Light microscopy nearly normal.

Electron microscopy shows podocyte foot-process effacement.

Usually steroid responsive.

Good prognosis.

Membranous nephropathy:

Important cause of adult nephrotic syndrome.

Diffuse capillary-wall thickening.

Subepithelial IgG/C3 deposits.

Spike-and-dome appearance.

PLA2R frequently involved in primary disease.

FSGS:

Focal and segmental glomerular scarring.

Proteinuria or nephrotic syndrome.

Hypertension may occur.

Higher risk of progressive CKD than typical minimal change disease.

IgA nephropathy:

Often young patients.

Visible haematuria during or immediately after respiratory infection.

Mesangial proliferation.

Mesangial IgA deposition.

MPGN:

May produce nephritic and nephrotic features.

Low complement may occur.

Mesangial/endocapillary proliferation.

Double-contour or tram-track appearance.

Modern classification divides disease into immune-complex and complement-mediated forms.

Post-streptococcal GN:

Acute nephritic syndrome.

Usually follows streptococcal infection after a latent period.

Low C3.

ASO or anti-DNase B evidence of recent infection.

Granular IgG/C3.

Subepithelial humps.

Rapidly progressive GN:

Rapid renal deterioration.

Crescent formation.

Type I = anti-GBM.

Type II = immune complex.

Type III = pauci-immune / ANCA associated.

Requires urgent investigation and treatment.

83. Important Corrections to the Original Notes

The statement:

“Minimal change GN is the most common”

should be changed to:

Minimal change disease is the most common cause of nephrotic syndrome in children.

The electron microscopy finding in minimal change disease is better called:

PODOCYTE FOOT-PROCESS EFFACEMENT

rather than simply:

“Fusion.”

The older term:

Mesangiocapillary GN

is now more commonly called:

MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS – MPGN.

The statement:

“60% have C3 nephritic factor”

should not be applied to all MPGN.

C3 nephritic factor is particularly associated with:

C3 glomerulopathy / alternative complement pathway dysregulation.

The older term:

Wegener’s granulomatosis

is now:

GRANULOMATOSIS WITH POLYANGIITIS – GPA.

The older terms:

ARF

and

ESRF

are better replaced with:

AKI – acute kidney injury

and

ESKD – end-stage kidney disease.

84. High-Yield Immunofluorescence Patterns

Minimal change disease:

Usually negative.

Membranous nephropathy:

Granular IgG and C3 along capillary walls.

IgA nephropathy:

Mesangial IgA deposition.

Post-infectious GN:

Granular IgG and C3.

Anti-GBM disease:

Linear IgG along GBM.

ANCA-associated GN:

Pauci-immune.

Little or no immune deposition.

85. High-Yield Electron Microscopy Patterns

Minimal change disease:

Foot-process effacement.

Membranous nephropathy:

Subepithelial deposits.

Spike-and-dome pattern.

Post-streptococcal GN:

Subepithelial humps.

MPGN:

GBM duplication / double contour.

Key Clinical Pattern

For nephrotic disease, remember:

MINIMAL CHANGE → CHILD + FOOT-PROCESS EFFACEMENT.

MEMBRANOUS → ADULT + SUBEPITHELIAL DEPOSITS + THICK GBM.

FSGS → FOCAL SEGMENTAL SCARRING + NEPHROTIC PROTEINURIA.

For haematuric/nephritic disease, remember:

IgA NEPHROPATHY → HAEMATURIA DURING OR IMMEDIATELY AFTER PHARYNGITIS.

PSGN → HAEMATURIA AFTER A LATENT PERIOD + LOW C3.

For rapidly progressive disease, remember:

TYPE I RPGN → ANTI-GBM → LINEAR IgG.

TYPE II RPGN → IMMUNE COMPLEX → GRANULAR DEPOSITS.

TYPE III RPGN → ANCA → PAUCI-IMMUNE.

The overall clinical clue is:

HAEMATURIA + PROTEINURIA + RBC CASTS + REDUCED GFR → THINK GLOMERULAR DISEASE.