Acute diffuse proliferative glomerulonephritis - Glomerular disease

Acute diffuse proliferative glomerulonephritis

Definition

A diffuse global glomerular disease, which is immune complex mediated and usually precipitated by a preceding infection.

Incidence

The commonest glomerulonephritis worldwide, falling in the United Kingdom.

Age

Any age, peak in schoolchildren.

Sex

M > F

Aetiology

The most common infectious agent is β-haemolytic Streptococcus, Lancefield Group A although other bacteria, viruses and malaria may be causative. A similar picture is seen in systemic lupus erythematosus.

Pathophysiology

There are subendothelial immune deposits of immune complexes, which may be derived from the circulation or formed de novo in the kidney. These result in complement activation and an inflammatory response, causing endothelial cell proliferation. Subepithelial deposits can lead to a variable degree of proteinuria.

Clinical features

The disease presents as acute nephritic syndrome (haematuria, oliguria and variable renal failure), with malaise and nausea 1–2 weeks after a illness such as a sore throat. Mild facial oedema and hypertension are variably present.

Macroscopy/microscopy

All the glomeruli demonstrate endothelial, epithelial and mesangial cell proliferation, together with neutrophils. Crescents may be formed in severe cases.

Immunofluorescence reveals granular deposits of C3 and IgG.

Electron microscopy shows subepithelial deposits (called humps or lumpy deposits).

Complications

Severe acute renal failure, rapidly progressive glomeru-lonephritis, hypertensive encephalopathy and pulmonary oedema.

Investigations

Renal biopsy is required to make a definitive diagnosis but may not always be necessary.

·        Throat swabs, swabs of skin lesions, anti-streptolysin O titre, anti-DNAse B antibodies and other tests may identify recent infection.

·        Low plasma complement especially C3.

Management

Antibiotics are usually given, although there is no evidence that they have an effect on the glomerulonephritis. There is no role for steroids or other specific treatments.

General measures are as for acute renal failure and nephritic syndrome. Dialysis may be required.

Prognosis

Most patients, especially children, have complete clinical resolution over 3–6 weeks, even in those with crescents on biopsy.

·        Up to 30% develop progressive renal disease, sometimes becoming manifest many years later with hypertension, recurrent or persistent proteinuria and chronic renal impairment. Late biopsy may show glomerulosclerosis, which is thought to be due to the loss of some glomeruli, leading to hyperfiltration through the remaining glomeruli, causing gradual changes to the glomeruli and ultimately renal failure. In other cases of persistent disease, the original glomerular disease may have been membranoproliferative glomerulonephritis.

·        Adults are more likely to develop rapidly progressive glomerulonephritis (>80% glomeruli affected) and have incomplete resolution afterwards.