What is rapidly progressive glomerulonephritis?

Rapidly progressive glomerulonephritis (RPGN) is one of the 7 types of chronic glomerulonephritis (GN). They are all ‘autoimmune diseases’ where the immune (defence) system attacks normal tissue in the kidney (including the glomeruli). Why and how they occur is unclear.

RPGN is not caused by a single disease. It has different causes (see below). Causes are classified by findings using kidney biopsy and the antibody blood tests below.

Patients with RPGN become unwell quite rapidly (as the name suggests); with Acute Kidney Injury (AKI) and rapid decline in kidney function (over days or weeks); haematuria and proteinuria (blood and protein in the urine; oliguria (reduced urine output, usually) and high blood pressure.

The pattern on kidney biopsy is usually a ‘crescentic glomerulonephritis’ (CGN), which means there are ‘crescents’ (crescent shaped scars) in > 50% of the glomeruli.

Who gets RPGN?

RPGN is relatively uncommon, affecting 10-15% of patients with glomerulonephritis. It is more common in White than Black or Asian people. The mean age of onset is around 30 years, but there is second peak in the late 60-70s.

Causes of RPGN

ANCA-associated vasculitis/RPGN

This is the commonest type which makes up 50% of all RPGN cases. Patients have antibodies called antineutrophil cytoplasmic antibodies (ANCAs), usually antiproteinase 3-ANCA or myeloperoxidase-ANCA.

Antiglomerular basement membrane antibody disease (Goodpasture syndrome)

Antiglomerular basement membrane (GBM) antibody disease accounts for up to 10% of RPGN cases.

The term Goodpasture syndrome refers to a combination of glomerulonephritis and lung haemorrhage (bleeding) associated with anti-GBM antibodies. The latter shows itself by coughing up blood. Goodpastures is an example of a ‘pulmonary-renal syndrome’ (see below).

Double-antibody disease

Patients with double-antibody disease have anti-GBM and ANCA antibodies. It is rare.

Pauci-immune RPGN

This is a term when a patient has RPGN but no antibodies, and they do not have this final category (below).

Immune-complex RPGN – caused by other diseases, and other types of chronic glomerulonephritis

RPGN can be a complication of numerous infections (e.g. infective endocarditis), cancers, drugs (e.g. hydralazine) and other systemic (whole body) autoimmune diseases, e.g. systemic lupus erythematosus (SLE) and forms of vasculitis such as Henoch-Schönlein purpura (HSP).

It can also be a presentation of other types of (primary) chronic glomerulonephritis (e.g. fibrillary glomerulonephritis, IgA nephropathy, membranous, mesangiocapillary and post-infectious glomerulonephritis). Like the underlying disease, why this happens, is unknown.

Further reading: Lionaki, 2020 (cancer-related RPGN)

Symptoms of RPGN

Initial symptoms are usually non-specific, with weakness, fatigue, fever, nausea, vomiting, anorexia (off food), arthralgia (joint pain), and abdominal pain. Some patients present similarly to those with postinfectious glomerulonephritis, with an abrupt-onset of haematuria (visible blood in the urine).

About 50% of patients have oedema (leg swelling) and a history of an upper respiratory infection (URTI) within 4 weeks of onset of the disease, usually followed by severe oliguria (lack of urine). 10-30% have severe proteinuria and therefore nephrotic syndrome is present. High blood pressure is uncommon and rarely severe.

Pulmonary-renal syndrome

Patients with RPGN (especially anti-GBM antibody disease) may present with upper or lower respiratory involvement. If the upper airways are involved, it may show itself as epistaxis (nose bleeding). If is lower airway, it causes pulmonary (lung) haemorrhage (bleeding). This can show itself as haemoptysis (coughing up blood), or be detectable only on a CXR, CT or MRI, or through a bronchoscopy (a tube put into the airways).

Diagnosis of RPGN

The diagnosis is made by a combination of medical assessment by a nephrologist (hospital-based kidney specialist) and blood, urine and other tests:

Kidney function tests – U+Es and glomerular filtration rate (GFR). These show rapidly (hence the name RPGN) progressive AKI/CKD (over days to weeks)
Antibodies (see below) – and complement (C3 and C4; complement is another part of the immune system) levels
Tests for infection – e.g. HIV, and Hepatitis B and C
Chest imaging – CXR, CT or MRI
Renal biopsy – this is essential.

Antibody testing should include:

Antineutrophil cytoplasmic antibodies (ANCA)
Anti-GBM antibodies (anti-GBM antibody disease)
ANA/dsDNA antibodies (for SLE)
Cryoglobulins (mixed essential cryoglobulinaemia)
Antistreptolysin O antibodies (post-infectious glomerulonephritis).

Early renal biopsy is essential. The feature common to all types of RPGN is increased number of cells (called ‘proliferation’) in the glomerulus. Characteristically, there are also crescent-shaped scars (‘crescents’) in > 50% of glomeruli.

Typical renal biopsy in RPGN, with a crescentic mass (crescent) of abnormal cells on the right on the upper biopsy and the base of the lower biopsy

Treatment of RPGN

Treatment options consist of a combination of some or all of these drugs or interventions:

Steroids (e.g. intravenous methylprednisolone)
Cyclophosphamide (a strong drug to suppress the immune system)
Rituximab (another strong immunosuppressant drug)
Plasma exchange.

Treatment varies by disease type, although no treatment regimes have been rigorously studied. Nonetheless immunosuppressive therapy with steroids and cyclophosphamide (or rituximab) is given to most patients with RPGN. Treatment should be started as soon as possible.

In addition, plasma exchange (also called plasmapheresis; daily 3- to 4-L exchanges for 14 days; a technique a bit like dialysis) is recommended for anti-GBM antibody disease. Plasma exchange may also be considered for some other causes of RPGN with pulmonary haemorrhage (or severe kidney dysfunction) on presentation – but its use remains controversial.

Dialysis and renal transplantation

Renal replacement therapy including dialysis may be required if AKI is severe. Some patients, if the disease responds to immunosuppression, can eventually come off dialysis.

Kidney transplantation is effective for all types, but disease may recur in the graft; risk diminishes with time. In anti-GBM antibody disease, the anti-GBM levels should be undetectable for at least 12 months before transplantation. For patients with other causes of RPGN, disease activity should be quiescent for at least 6 months before transplantation; ANCA levels do not need to be suppressed.

Greenhall, 2015
KDIGO, 2021

Prognosis (outlook) of RPGN

It is a serious disease and permanent dialysis (or a kidney transplant) is required in 20-40% of patients. Spontaneous remission (getting better with no treatment) is rare.

Anti-GBM disease is usually quickly fatal if untreated. Patient survival is greatly improved with treatment and is as high as 90%. Prognosis improves with early treatment – the earlier the better.

Mortality in untreated pauci-immune RPGN is 90% without therapy, although treatment is effective and has reduced mortality to 10-20%.

Wu, 2019 (prognosis)

Summary

We have described what is rapidly progressive glomerulonephritis. We hope it has been useful.

Other resources

What is chronic glomerulonephritis?
What is minimal change disease?
What is membranous nephropathy?
What is FSGS?
What is IgA nephropathy?
What is post-infectious glomerulonephritis?
What is mesangiocapillary glomerulonephritis?

These are review articles for health professionals:

Hruskova, 2018 (RPGN in elderly)
Murshed, 2021
Moorani, 2022 (RPGN in children)
Naik, 2023
O’Brien, 2023.

Last Reviewed on 24 May 2024