78. Rapidly progressive glomerulonephritis

Definition

Rapidly progressive glomerulonephritis (RPGN) is a subtype of acute glomerulonephritis which is rapidly progressive. The kidney function is rapidly decreasing, that is, it would lead to end-stage renal disease in weeks if left untreated. The blood pressure is rapidly increasing as well. Histology is required for diagnosis. Early diagnosis and treatment are required to limit irreversible kidney injury.

RPGN is sometimes called crescentic glomerulonephritis because of the characteristic half-moon shapes which are present on histology.

Etiology

RPGN is classified into three types, based on the pathomechanism and immunohistological findings:

  • Type I – Anti-GBM-associated RPGN
    • Anti-GBM glomerulonephritis
    • Goodpasture syndrome
  • Type II – Immune complex-mediated RPGN
    • Infection
    • SLE
    • Henoch-Schönlein purpura (IgA vasculitis)
    • Cryoglobulinaemia
    • IgA nephropathy (rare)
  • Type III – Pauci-immune RPGN or ANCA vasculitis-associated RPGN
    • Microscopic polyangiitis (MPA)
    • Granulomatosis with polyangiitis (GPA)
    • Eosinophilic granulomatosis with polyangiitis (EGPA)

Of these, type III is the most common (60 – 70%), and of these, MPA is the most common.

Both anti-GBM glomerulonephritis and Goodpasture syndrome are characterised by RPGN and anti-GBM antibodies, but only Goodpasture has alveolar haemorrhage with resulting haemoptysis.

IgA nephropathy most commonly causes chronic GN, but in rare cases can cause RPGN.

Pathomechanism and histology

When examined histologically after a biopsy, crescents (half-moon shapes) are present in the glomeruli and are characteristic for RPGN. These crescents are formed from proliferating cells which displace the glomerulus.

In untreated cases, these cells continue to proliferate, causing the crescents to continuously grow. They eventually compress and reduce the circulation, causing irreversible necrosis. Eventually the whole glomerulus will be destroyed. Treatment must be initiated before the process becomes irreversible.

While normal histology is enough to diagnose RPGN, immunohistology (immune fluorescence) is required to separate the three types of RPGN:

Type I RPGN is associated with anti-glomerular basement membrane antibodies. On immunohistology there is linear deposition of IgG along the glomerular basement membrane.

Type II RPGN is associated with deposition of immune complexes in the glomeruli. On immunohistology there is granular deposition of IgG along the glomerular basement membrane.

Type III RPGN is associated with ANCA-associated vasculitis, but there is no deposition of antibodies in the glomerular basement membrane. As such, immunohistology is negative or almost negative. Pauci-immune means “few-immune”.

Clinical features

Patients usually initially experience non-specific symptoms like fatigue and myalgia. Later, patients experience more severe symptoms like oliguria and symptoms of nephritic syndrome like oedema and haematuria, which prompts the need for rapid evaluation.

If RPGN is caused by Goodpasture syndrome or ANCA-associated vasculitis, the patient may experience haemoptysis. This is called kidney-lung or pulmonary-renal syndrome.

Diagnosis and evaluation

Due to the rapidly decreasing kidney function, creatinine levels are elevated.

Like for acute glomerulonephritis, screening lab tests are used to screen for cause:

  • C3 and C4 – for PSGN
  • Antinuclear antibodies (ANA) – for SLE
  • Anti-dsDNA antibodies – for SLE
  • c-ANCA and p-ANCA – for ANCA-associated vasculitis
  • Cryoglobulins – for cryoglobulinaemia
  • Anti-GBM – for anti-GBM disease
  • Serology for HIV, HBV, HCV
  • Serum free light chains – for amyloidosis

Rapidly progressive glomerulonephritis is one of the indications for kidney biopsy, and so kidney biopsy is performed in all cases. Histology allows us to diagnose RPGN and immunohistology allows us to determine which type of RPGN is present.

Kidney biopsy cannot show the specific cause, and so clinical features and other examinations like lab tests and other biopsies are required for this, but that is not usually urgent as the priority is to treat the RPGN.

c-ANCA is more associated with GPA, while p-ANCA is more associated with MPA and EGPA.

Chest CT or MR should be used in case of kidney-lung syndrome.

Treatment

The treatment for RPGN depends on the type, and so determining the type as soon as possible is important.

Generally, methylprednisolone + cyclophosphamide is used to achieve remission. If there are lung manifestations (haemoptysis), plasma exchange therapy is added. If RPGN due to infection, methylprednisolone + antibiotic is used.

To maintain remission, azathioprine and a low dose steroid is often used.

Prognosis

Postinfectious RPGN may be cured, but in most cases of RPGN lifelong immunosuppressive therapy is necessary to prevent further kidney function loss. In most cases, the patient’s renal function stabilizes at a moderately impaired level for years.


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77. Acute glomerulonephritis

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79. Nephropathies associated to systemic illnesses (SLE nephropathy, vasculitis, atherosclerosis, hemolytic uremic syndrome)

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