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IgA Nephropathy

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Overview

Also known as Berger’s disease, IgA nephropathy describes the clinical manifestations of immunoglobulin A (IgA)-containing immune complex deposits in the mesangium of the glomerulus (type III hypersensitivity). It is closely related to IgA vasculitis (Henoch–Schönlein purpura), which can be thought of as the systemic form of IgA nephropathy. Its pathogenesis is not fully understood.

Most patients with IgA nephropathy present with recurrent haematuria following an upper respiratory tract infection (URTI) or gastroenteritis. Less than 10% of patients may present with rapidly progressive glomerulonephritis (RPG).

Epidemiology

  • IgA nephropathy is the most common glomerulonephritis globally
  • Most cases are diagnosed between the ages of 16-35 years
  • IgA nephropathy is more common in men

Risk Factors

  • Recent URTI or gastroenteritis
    • Thought to be due to mucosal immune system dysfunction, as IgA plays a key role in the immune function of mucous membranes
  • IgA vasculitis
    • May cause kidney disease
  • Chronic liver disease
    • Thought to be due to impaired hepatic IgA clearance

Presentation

Patients classically present with recurrent episodes of macroscopic (usually painless) haematuria following a URTI or gastroenteritis. Other features include:

Differential Diagnoses

Post-streptococcal glomerulonephritis (PSGN)

  • Proteinuria is more common in PSGN, but haematuria may still occur
  • Hypertension is more common in PSGN
  • IgA nephropathy tends to develop around 1-2 days following a URTI, PSGN tends to develop around 1-3 weeks following a URTI
  • Anti-streptolysin O may be elevated in PSGN
  • C3 may be low in PSGN

IgA vasculitis (Henoch-Schönlein purpura, HSP)

  • IgA vasculitis has characteristic symptoms of a purpuric rash, abdominal pain, and joint pain, whereas IgA nephropathy does not
  • Although both have similar histopathological findings, evidence of IgA-containing immune complex deposition outside of the kidneys suggests IgA vasculitis

Investigations

  • Urinalysis:
    • May show red blood cells
    • May show protein – important in predicting the outcome
  • Urine microscopy and culture:
  • Urea and electrolytes (U&Es) and estimated glomerular filtration rate (eGFR):
    • May be deranged depending on disease progression
  • C3 and C4 complement levels:
    • To rule out another immune complex glomerulonephritis such as PSGN
  • Renal ultrasound:
    • May be considered to rule out structural abnormalities
  • CT kidney, ureter, and bladder:
    • May be considered to rule out structural abnormalities
  • Flexible cystoscopy:
    • May be considered in older patients (>40 years) to rule out bladder cancer
  • Kidney biopsy – required to make a diagnosis of IgA nephropathy:
    • Shows mesangial IgA deposition
    • IgA nephropathy cannot be diagnosed without a biopsy

Management

No universal management steps are in place for IgA nephropathy. Management may include:

  • Renal function normal, <0.5 g/day proteinuria, normal eGFR and isolated haematuria:
    • Observe and monitor kidney function and blood pressure
  • Proteinuria >0.5 g/day:
    • Start angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs)
  • Nephrotic range proteinuria (>3.5 g/day):
  • Acute kidney injury (AKI):
    • Supportive management
  • AKI with crescenteric IgA nephropathy:
    • Treat as renal vasculitis with corticosteroids and cyclophosphamide

Complications

Chronic kidney disease (CKD)

IgA nephropathy can lead to CKD and may progress to end-stage renal disease (ESRD) in around 30% of patients 20 years after diagnosis

Acute kidney injury (AKI)

AKI is uncommon. It may occur if IgA nephropathy presents as an RPG

Prognosis

  • Around 30% of patients with IgA nephropathy progress to ESRD within 20 years
  • The prognosis is worse in those with increasing proteinuria
  • Interestingly, recurrence can happen after renal transplantation, suggesting the problem is with the immune system rather than the kidney itself

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