Acute nephritic syndrome (acute glomerulonephritis, acute nephritis syndrome)

• Disease Site
• Incidence
• Predisposing Factors
• Macroscopic Features
• Microscopic Features
• Clinical History
• Clinical Examination
• Specific Investigations
• Prognosis
• Treatment Overview
• References
• Drugs/Products Associated with Acute Nephritic Syndrome

Disease Site

Acute nephritic syndrome is a group of disorders that cause inflammation of the internal kidney structures (specifically, the glomeruli).

Incidence

Acute nephritic syndrome (ANS) is uncommon in developed countries due to improved hygiene and decreased post-streptococcal and other post-infection glomerulonephritis. However, it is still a common presentation in developing countries.

Children between 2 and 12 are most commonly affected, but it may occur at any age. Males are more commonly affected, especially with the more severe cases.

Predisposing Factors

Infections with Group A Streptococcal bacteria (APSGN)

In warm climates, the disease most commonly follows infected skin lesions and occurs more often in the summer. In cold climates, the disease occurs more frequently as a result of streptococcal throat infection during the winter months. The risk of developing acute nephritic syndrome depends on the type of streptococcal bacteria.

Other causes

There are a variety of other causes of ANS, including:

• Primary renal diseases:
  • Immunoglobulin A nephropathy;
  • Membranoproliferative glomerulonephritis;
  • Idiopathic rapidly progressive glomerulonephritis (crescentic glomerulonephritis).
• Secondary renal diseases:
  • Subacute bacterial endocarditis;
  • Infected ventriculoperitoneal shunt;
  • GN with visceral abscess;
  • GN with bacterial, viral or parasitic infections.
• Multi-system disease:
  • Systemic lupus erythematosus (SLE);
  • Granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis);
  • Goodpasture’s syndrome;
  • Microscopic polyarteritis;
  • Mixed cryoglobulinaemia;
  • Henoch-Schonlein purpura;
  • Haemolytic uraemic syndrome.
• Allergy:
  • Acute allergic tubulointerstitial nephritis.

Macroscopic Features

There are no evident macroscopic changes of the kidneys in ANS.

Microscopic Features

Deposition of immune complexes in the glomerulus leads to an inflammatory response which triggers secondary mechanisms of glomerular injury. This includes complement activation, fibrin deposition, platelet aggregation and activation of kinin systems. The histological response is quite variable.

Post-streptococcal GN

Diffuse glomerulonephritis resulting from proliferation of endothelial, mesangial and epithelial cells and from exudation of neutrophils and monocytes.

Anti-basement membrane disease

Crescents result from parietal epithelial cell proliferation and monocyte infiltration in Bowman’s space. Fibrin is universally present.

Clinical History

• ANS presents with haematuria and evidence of acute renal dysfunction (oedema, oliguria, hypertension, reduced renal function).
• A detailed medication, occupational, environmental and family history is necessary.
• Symptoms suggestive of recent streptococcal pharyngitis or impetigo should be sought.
• The latent periods after pharyngitis and skin infections are 1-2 weeks and 3-6 weeks respectively.
• Vasculitis findings: Skin rashes, arthralgia or arthritis, pulmonary lesions and peripheral nerve deficits.
• Illicit drug use/hydrocarbon exposure (rare associations.)
• Acute tubulointerstitial nephritis secondary to a drug reaction may present with ANS.
• In hereditary complement deficiency states, there is increased familial incidence of acute GN.

Clinical Examination

It is important to identify complications. Most patients have hypertension. Pulmonary and peripheral oedema are frequent complications, both associated with a relatively high morbidity and mortality rate

Findings of vasculitis: rashes, petechiae, joint swelling, joint pain and peripheral nerve dysfunction.

Specific Investigations

• Urine chemistry – low fractional sodium excretion.
• Renal imaging – normal to large kidneys (excludes chronic renal disease).
• Coagulation profile – transient low C3 in many of the causes.
• Anti-streptolysin O titre (ASOT) – serology for evidence of recent streptococcal infection.
• Throat culture – for streptococcus.

Screening for other systemic diseases

• Antinuclear and anti-DNA antibodies for SLE and anti-glomerular basement membrane antibodies in renal limited disease and Goodpasture’s syndrome.
• Anti-neutrophil cytoplasmic antibodies in other vasculitic syndromes.

Renal biopsy

• When in doubt about the diagnosis or if there is suspicion of rapidly progressive glomerulonephritis, a renal biopsy is the gold standard for diagnosis.

Prognosis

The prognosis of post-streptococcal glomerulonephritis is good. The Outcome in ANS associated with SLE, systemic vasculitis and Goodpasture’s syndrome is less favourable. The risk of progression to end stage renal failure with post-streptococcal glomerulonephritis is very small for children but becomes worse with increasing age. In adults, 5% have persistent proteinuria, hypertension and reduced renal function. Some of these may progress to end-stage renal failure.

Treatment Overview

The principles of managing this condition include:

• Control and prevention of elevated blood pressure: The presence of hypertension can increase the rate of deterioration of renal function in this condition. Treatment may involve the use of anti-hypertension medications, and restriction of fluid and salt from the diet.
• Anti-inflammatory and immunosuppressant therapy: To control the inflammatory process of some causes of nephritic syndrome, including vasculitis.
• Supportive therapy for renal failure: Blood tests will be required regularly to ensure that renal failure is diagnosed and controlled early. Dialysis may be required if the renal failure cannot be controlled by conservative means.
• Antibiotic therapy: For those with proven post-streptococcal nephritic syndrome.

Treatments used in this disease:

• Kidney Transplant

References

1. Braunwald E, Fauci AS, Kasper DL, et al. Harrison’s Principles of Internal Medicine (15th edition). New York: McGraw-Hill Publishing; 2001. [Book]
2. Cotran RS, Kumar V, Collins T, Robbins SL. Robbins Pathologic Basis of Disease (6th edition). Philadelphia: WB Saunders Company; 1999. [Book]
3. Hurst JW (ed). Medicine for the Practicing Physician (4th edition). Norwalk, CT: Appleton and Lange; 1996. [Book]
4. Kumar P, Clark M (eds). Clinical Medicine (5th edition). Edinburgh: WB Saunders Company; 2002. [Book]
5. Longmore M, Wilkinson I, Rajagopalan S. Oxford Handbook of Clinical Medicine (5th edition). Oxford: Oxford University Press; 2001. [Book]

Drugs/Products Used in the Treatment of This Disease

• BenPen (Benzylpenicillin sodium)
• Captopril (Captopril)
• Lasix (Frusemide)