Glomerulonephritis

 

• Background

  Definition and classification

  • Inflammation of the glomeruli.
  • This page discusses primary glomerulonephritides, but glomerular disease can also be secondary to diabetes and multi-system autoimmune or infiltrative diseases.
  • Can be classified by whether they typically present with nephrotic syndrome – minimal change disease, membranous GN, membranoproliferative GN, FSGS – or haematuria/nephritic syndrome – IgA nephropathy, post-streptococcal GN, rapidly progressive GN. However, presentation is often non-specific and asymptomatic.

  Presentation

  • Can be an incidental finding in an asymptomatic individual e.g. with hypertension, proteinuria or haematuria on dipstick, abnormal renal function test, anaemia.
  • Symptomatic presentations include oedema (nephrotic syndrome), frank haematuria, or generally unwell (uraemia, anaemia).

  Management

  • See chronic kidney disease (CKD) and/or acute kidney injury (AKI) for general management of renal impairment. BP control (SBP <130) and ACEi/ARB therapy (esp. if proteinuric) is particularly important.
  • The sections below outline which types of GN may benefit from immunosuppression.

• Minimal change disease

  Pathophysiology and epidemiology

  • Pathology: podocyte effacement seen on electron microscopy.
  • Commonest cause (90%) of nephrotic syndrome in children.
  • Causes: idiopathic, Hodgkin's lymphoma, NSAIDs, lithium.

  Management and prognosis

  • Usually responds to corticosteroids, especially in kids (90%). 2nd line cyclophosphamide or calcineurin inhibitors (tacrolimus, ciclosporin).
  • Although relapses are common, long-term prognosis is good.

• Membranous glomerulonephritis

  Pathophysiology and epidemiology

  Diffuse thickening of glomerular basement membrane, due to:

  • Autoimmune reaction to phospholipase A2 receptor (PLA2R) or other podocyte autoantigens.
  • Cancer: lung, prostate, Hodgkin's.
  • Infection: HBV, HCV, TB, malaria.
  • Drugs: NSAIDs, anti-malarials, gold, penicillamine.
  • SLE

  Commoner in adults.

  Management and prognosis

  • Untreated, 50% self-resolve and 50% progress to end-stage kidney disease.
  • Given potential for resolution, only treat in severe nephrotic syndrome, with corticosteroids plus cyclophosphamide.

• Membranoproliferative glomerulonephritis

  Aka mesangiocapillary glomerulonephritis.

  Pathophysiology and epidemiology

  • Mesangial proliferation (capillary smooth muscle cell proliferation) and thickened glomerular basement membrane.
  • Causes: idiopathic, SLE, HBV/HCV, monoclonal gammopathy, lymphoma.
  • Relatively uncommon. Usually occurs in children or young adults.

  Presentation and prognosis

  • Presents with nephrotic (50%) or nephritic (30%) syndrome, or sometimes just isolated protein- and haematuria.
  • 50% develop end-stage kidney disease in 10 years.

• Focal and segmental glomerulosclerosis (FSGS)

  Pathophysiology

  • Accumulation of type 4 collagen (sclerosis) in parts (segmental) of some (focal) glomeruli.
  • Typically leads to nephrotic syndrome.
  • Causes: idiopathic, cancer, HIV, obesity.

  Management and prognosis

  • 50% respond to corticosteroids.
  • Further immunosuppression (ciclosporin, cyclophosphamide, MMF, or rituximab) may be beneficial in steroid-resistant FSGS, but many progress to end-stage kidney disease.

• IgA nephropathy

  Aka Berger's disease.

  Pathophysiology and epidemiology

  • A type of mesangial proliferative nephritis, involving glomerular IgA deposition.
  • Commonest type of glomerulonephritis worldwide.
  • Henoch-Schonlein purpura is sometimes considered a systemic form, as it causes renal IgA deposition.

  Presentation

  • Around 50% present with visible haematuria in the days following an URTI, which is thought to trigger the disease. Flank pain may be present.
  • Remainder mostly present with incidental microscopic haematuria ± proteinuria.
  • Rarely, presents with nephrotic syndrome or rapidly progressive glomerulonephritis (RPGN).

  Management

  Corticosteroids for those with rapidly progressive disease, otherwise benefit is unclear.

• Post-streptococcal glomerulonephritis

  • Typically 1-2 weeks after pharyngitis or (less commonly) impetigo.
  • Usually presents with haematuria or nephritic syndrome, but can also lead to rapidly progressive glomerulonephritis.