IgA nephropathy

Definition

IgA nephropathy (Berger disease) is a chronic glomerulonephritis with deposition of IgA-containing immune complexes in the glomerular mesangium. It presents with slowly progressive hematuria and proteinuria and may lead to chronic kidney disease.

Occurrence & epidemiology

IgA nephropathy is the most common form of glomerulonephritis worldwide. It is more common in Asia and some European countries than in Africa and South America. Onset peaks in the third and fourth decades of life (ages 20 to 39); men are generally affected more often than women.

Aetiopathogenesis

The cause is not fully understood. Proposed mechanisms include increased production of IgA1, defective IgA1 glycosylation with increased binding to mesangial cells, reduced clearance of IgA1, a disturbed mucosal immune system and cytokine-mediated proliferation of mesangial cells. Familial clustering suggests genetic factors. Renal IgA deposits are also found in many healthy people; not everyone with such deposits develops clinical disease.

Mesangial IgA deposits also occur secondarily, e.g. in IgA vasculitis, liver cirrhosis, inflammatory bowel disease, celiac disease, psoriasis and HIV infection. IgA vasculitis differs clinically by purpura, joint pain and abdominal pain.

Clinical features

• Episodic gross hematuria, typically 1–2 days after a febrile mucosal infection (respiratory tract, sinuses, gut): "synpharyngitic" hematuria, often with flank pain and low-grade fever. The latency is shorter than in postinfectious glomerulonephritis.
• Asymptomatic microscopic hematuria with mild proteinuria as an incidental finding
• Less common presentations: nephrotic syndrome (about 10%), rapidly progressive glomerulonephritis as initial presentation (about 5%), acute kidney injury, severe hypertension or chronic kidney disease

Histology

Immunofluorescence shows granular deposits of IgA and complement C3 in an expanded mesangium. Light microscopy shows mesangial expansion and focal segmental proliferative or necrotizing lesions.

Diagnosis

• Urine sediment: microscopic hematuria, usually with dysmorphic red cells, occasionally red blood cell casts
• Proteinuria: typically mild (< 1 g/day); it may also occur without hematuria.
• Blood: creatinine usually normal, complement normal; an elevated serum IgA is not diagnostically helpful.
• Kidney biopsy: confirms the diagnosis when manifestations are moderate or severe

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Further reading (open access)

1. MSD Manual Professional: Immunoglobulin A Nephropathy

Cross-references