Glomerulonephritis

Glomerulonephritis refers to a disease affecting the glomeruli, even though inflammation itself (-itis) is not necessarily present. Glomerulonephritis is rare, and it can cause severe symptoms and chronic kidney disease.

Glomerulonephritis causes acute glomerulonephritis syndrome, sometimes called just nephritic syndrome. According to the definition of glomerulonephritis syndrome, the following clinical features are present:

• Glomerular haematuria
• Proteinuria (usually mild)
• Decreased kidney function (GFR)
• Increased blood pressure
• Periorbital oedema
• Bilateral kidney enlargement

Not all features must necessarily be present.

Etiology

• Secondary to infectious diseases
  • Acute poststreptococcal glomerulonephritis
  • Endocarditis
  • GN associated with other infections (staph, pneumococcus, viruses, etc.)
• Secondary to systemic autoimmune diseases
  • ANCA-associated vasculitis
  • SLE
  • Cryoglobulinaemia
• Primary glomerulonephritis (rare)
  • IgA nephropathy
  • Membranoproliferative glomerulonephritis

Acute poststreptococcal GN (PSGN) is less and less common as we treat all streptococcal diseases with antibiotics nowadays before PSGN develops. On the other hand, GN associated with other infections are becoming more common.

PSGN usually occurs 1 – 4 weeks after streptococcal infection like streptococcal pharyngitis.

IgA nephropathy is the most common cause of chronic GN, but rarely it can cause acute GN as well. Membranoproliferative glomerulonephritis also most commonly cause chronic GN.

Pathomechanism

Glomerulonephritis is associated with destruction of the glomerular basement membrane (GBM). In most cases, the destruction is due to deposition of immune complexes in the GBM, which causes local inflammation and destruction.

For poststreptococcal GN, immune complexes containing streptococcal antigens deposit in the GBM, because of molecular mimicry between the streptococcal antigens and antigens in the GBM.

Clinical features

The clinical features of acute glomerulonephritis are those of nephritic syndrome, which was described earlier.

In cases of secondary GN, the patient will have experience symptoms and signs of the underlying condition.

Diagnosis and evaluation

Glomerular haematuria refers to the presence of so-called glomerular RBCs in the urine. These are dysmorphic RBCs with an abnormal morphology, where “blebs” form on the surface of the RBCs, giving them a “Mickey Mouse”-outline. RBC casts are sometimes present. In contrast, non-glomerular haematuria consists of RBCs with normal morphology and no RBC casts.

It’s important to determine the cause of acute GN. In most cases however, kidney biopsy is not required for the diagnosis. With a typical clinical picture and the lab tests described below the diagnosis can usually be made clinically.

Certain lab tests are performed in most cases of GN where the underlying cause is not immediately obvious. These screening tests can help determine the 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

Antistreptococcal antibodies (ASO titre) can be used for diagnosis of PSGN.

Kidney biopsy is indicated in cases where glomerulonephritis is suspected but the underlying cause cannot be determined with other examinations. Primary GN required kidney biopsy for diagnosis.

Treatment

All cases of glomerulonephritis must be treated to prevent complications, but the treatment involves treating the underlying cause. PSGN spontaneously resolves with treatment of the underlying bacterial infection.

Non-specific renal protective treatment may be necessary in case of proteinuria or hypertension. RAAS blockers are often used because they reduce both proteinuria and hypertension. Diuretics can also be used in case of oedema or hypertension.

Complications

• Rapidly progressive glomerulonephritis
• Acute kidney injury
• Chronic kidney disease

Acute GN can present with acute kidney injury or rapidly progressive glomerulonephritis.

Prognosis

The prognosis of glomerulonephritis is better in children than in adults. Most (> 90%) of children recover completely, while approx. 50% of adults suffer from permanently reduced kidney function.