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Glomerulonephritis

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What is glomerulonephritis?

Glomerulonephritis (GN) is a renal disease characterised by inflammation and damage to the glomeruli. This glomerular damage allows protein (+/- blood) to leak into the urine (proteinuria and haematuria respectively)

Glomerulonephritis can present with any of the following:

  • Isolated haematuria or proteinuria
  • Nephrotic syndrome (severe proteinuria, oedema, hypoalbuminaemia, hyperlipidemia and hypertension)
  • Nephritic syndrome (haematuria, hypertension, oliguria, red cell casts and mild to moderate proteinuria)
  • Acute renal failure
  • Chronic renal failure

Glomerulonephritis (GN) can be broadly categorised into proliferative and non-proliferative disease. This article provides a brief overview of the various subtypes of both proliferative and non-proliferative GN.


Non-proliferative glomerulonephritis

Non-proliferative glomerulonephritis is characterised by a lack of glomerular cell proliferation and typically presents with nephrotic syndrome.

Minimal change glomerulonephritis

  • Minimal change glomerulonephritis presents with nephrotic syndrome.
  • It accounts for 80% of all nephrotic syndrome in children and 20% of nephrotic syndrome in adults.
  • The underlying cause of minimal change glomerulonephritis is unknown.

Typical investigation findings

  • Urinalysis – proteinuria
  • Light microscopy – no visible abnormalities
  • Immunofluorescence – no immunoglobulins or complement deposits bound to the kidney tissue ¹
  • Electron microscopy – diffuse loss of visceral epithelial cells’ foot processes (i.e. podocyte effacement), vacuolation, and growth of microvilli on the visceral epithelial cells, allowing for excess protein loss in the urine ²

Management

  • Supportive care – nutritional support, salt and fluid restriction
  • Corticosteroids (first-line) – used in both adults and children (more data for efficacy in children) ¹
  • Other immunosuppressants (second-line – effectiveness unclear) – e.g. calcineurin inhibitor, mycophenolate mofetil, rituximab ¹

Focal segmental glomerulosclerosis (FSGS)

  • Typically presents with nephrotic syndrome(usually haematuria, hypertension and impaired renal function)
  • Aetiology:
    • Primary FSGS (i.e. genetic mutations)
    • Secondary FSGS (e.g. HIV, lupus, reflux nephropathy)

Typical investigation findings

  • Specific segments of certain glomeruli show segmental scarring in addition to foot process fusion

Management

  • Supportive care – salt restriction and fluid management
  • High-dose prednisolone (approximately 50% of patients respond – treatment can be up to 4 months in adults)
  • Additional cyclophosphamide or ciclosporin is used in some cases to reduce proteinuria.

Prognosis

  • Typically progresses to end-stage kidney disease over the course of several years in up to 50% of patients
  • Corticosteroids can halt progression in some cases

 

Membranous glomerulonephritis

  • Membranous glomerulonephritis typically presents with nephrotic syndrome
  • It is usually a slowly progressive disease primarily affecting individuals between the ages of 30-50
  • It is most commonly idiopathic but can be associated with hepatitis B, malaria and system lupus erythematosus (SLE)

Pathophysiology

  • Immune complex deposition, resulting in complement activation against glomerular basement membrane proteins

Typical investigation findings

  • Microscopic analysis shows thickened glomerular basement membrane
  • Immunofluorescence shows diffuse uptake of IgG 

Management

  • Corticosteroids are often used to treat progressive disease

Prognosis

  • 1/3 have chronic membranous glomerulonephritis
  • 1/3 go into remission
  • 1/3 progress to end-stage renal failure

Proliferative glomerulonephritis

  • Proliferative glomerulonephritis is characterised by increased numbers of cells in the glomerulus
  • It typically presents with nephritic syndrome

IgA nephropathy

  • IgA nephropathy is also known as Berger’s disease
  • It is the most common type of GN in adults worldwide
  • It typically presents as nephritic syndrome (macroscopic haematuria) 24-48 hours after an upper respiratory tract infection

Typical investigation findings

  • Microscopically the disease is characterised by:
    • increased numbers of mesangial cells
    • increased matrix (the cellular scaffolding that holds everything together)
  • Immunohistochemistry reveals IgA deposition in the matrix.

Management

  • Some studies suggest that a course of high-dose prednisolone can reduce proteinuria and delay renal impairment
  • In patients with deteriorating renal function, immunosuppressive drugs are also often used

Prognosis

  • Prognosis is variable, with 20-30% of patients progressing to end-stage renal failure

 

Post-infectious glomerulonephritis

  • Post-infectious glomerulonephritis (PIGN) is an immunologically mediated glomerular injury triggered by an infection
  • PIGN is most commonly associated with streptococcal infections (referred to as post-streptococcal glomerulonephritis)
  • The disease typically presents approximately 2 weeks after infection with nephritic syndrome (i.e. gross haematuria, oliguria, oedema)

Typical investigation findings

  • Diffuse proliferative and exudative glomerular histology
  • Dominant C3 staining and subepithelial humps

Diagnosis

Diagnosis is typically based on the presence of:

  • Symptoms and signs of GN
  • History of recent infection (e.g. streptococcal)
  • Raised streptococcal titres 

Management

  • Management is largely supportive, with careful monitoring of fluid balance

Prognosis

  • PIGN is usually a self-limited disease, especially in children, but long-term follow-up studies indicate persistent low-grade renal abnormalities in a significant proportion of patients. 3

Membranoproliferative glomerulonephritis

  • Membranoproliferative glomerulonephritis is a group of immune-mediated disorders characterised histologically by glomerular basement membrane (GBM) thickening and proliferative changes on light microscopy.
  • It should not be confused with membranous glomerulonephritis, a condition in which the basement membrane is thickened, but the mesangium is not.
  • The disease is associated with hepatitis C and several autoimmune conditions including systemic lupus erythematosus (SLE).

Typical investigation results

Microscopy:

  • Thickened basement membrane
  • Thickened mesangium
  • “Tram tracking” appearance

Immunofluorescence:

  • Subendothelial deposition of IgG

Management

  • Children (with nephrotic-range proteinuria) – corticosteroids
  • Adults (dipyridamole and aspirin)
  • Kidney transplantation for patients with end-stage renal disease

 

Rapidly progressive glomerulonephritis (crescentic glomerulonephritis)

  • Rapidly progressive glomerulonephritis (RPGN) is acute nephritic syndrome accompanied by microscopic glomerular crescent formation with progression to renal failure within weeks to months.
  • RPGN is relatively uncommon, affecting 10 to 15% of patients with glomerulonephritis
  • It primarily occurs in patients aged 20 to 50 years
Crescentic glomerulonephritis
Crescentic glomerulonephritis 4

 

Anti-glomerular basement membrane antibody disease (Anti-GBM)

  • Anti-GBM disease is an immune-mediated pathology involving antibodies directed against glomerular basement membrane antigens (anti-GBM antibodies).
  • These antigens are located in the glomeruli and in the alveoli of the lungs.
  • A cell-mediated inflammatory response occurs as a result of the anti-GBM antibodies which can affect both the kidneys (nephritic syndrome) as well as the lungs (alveolar haemorrhage presenting with haemoptysis).
  • If the lungs and kidneys are involved the condition is known as Goodpasture’s syndrome.
  • Anti-GBM disease accounts for approximately 10% of RPGN.
  • Progression to renal failure is often rapid without medical intervention.

Typical investigation results

  • Immunohistochemistry –IgG deposits along the basement membrane of the glomerulus
  • Antibodies – anti-GBM antibodies

Management

High dose immunosuppression is required:

  • IV prednisolone
  • Cyclophosphamide
  • Plasmapheresis

 

Vasculitic disorders

Granulomatosis with polyangiitis

  • Granulomatosis with polyangiitis (GPA), previously known as Wegener’s granulomatosis, is an extremely rare long-term systemic disorder that involves the formation of granulomas and inflammation of blood vessels (vasculitis)
  • It is a form of vasculitis that affects both small and medium-sized vessels in many organs (commonly the upper respiratory tract, lungs and kidneys) 5
  • Symptoms are highly variable, depending on which vessels are affected
  • GPA affecting the lungs, kidneys or heart can be life-threatening
  • The vasculitis is caused by anti-neutrophil cytoplasmic antibodies (c-ANCA)

Diagnosis

  • A history of unexplained symptoms
  • Positive c-ANCA test
  • Biopsy (e.g. of kidney or cutaneous tissue) – leukocytoclastic vasculitis with necrotic changes and granulomatous inflammation (clumps of typically arranged white blood cells) on microscopy

Management

  • Induction of remission – rituximab or cyclophosphamide in combination with high dose corticosteroids
  • Maintenance – methotrexate and corticosteroids

 

Microscopic polyangiitis

  • A systemic small-vessel vasculitis without clinical or pathological evidence of necrotising granulomatous inflammation
  • Clinical features can include weight loss, fevers, fatigue and renal failure
  • Ongoing inflammation is driven by anti-neutrophil cytoplasmic antibodies (p-ANCA)

Diagnosis

  • Raised ESR and CRP
  • Anaemia
  • p-ANCA is positive in almost all cases

Management

  • Long-term prednisolone and cyclophosphamide therapy (often cycled)
  • Plasmapheresis can be helpful acutely to remove p-ANCA antibodies

References

  1. Johnson, Richard J.; Feehally, John; Floege, Jürgen (2018-06-26). Comprehensive clinical nephrology (Sixth ed.). Edinburgh. ISBN 9780323547192. OCLC 1047958109.
  2. Fogo, Agnes B.; Lusco, Mark A.; Najafian, Behzad; Alpers, Charles E. (Aug 2015). “AJKD Atlas of Renal Pathology: Minimal Change Disease”. American Journal of Kidney Diseases. 66 (2): 376–377. doi:10.1053/j.ajkd.2015.04.006. ISSN 1523-6838. PMID 26210726.
  3. Kambham N. Postinfectious glomerulonephritis. Published September 2012. Available from: [LINK] https://www.ncbi.nlm.nih.gov/pubmed/22885383
  4. Nephron. Crescentic glomerulonephritis. Available from: [LINK]. Licence: CC BY-SA

 

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