IgA glomerulonephritis
IgA nephropathy (aka Berger disease) is the most frequent form of idiopathic glomerulonephritis worldwide.
IgA comes in two subclasses, IgA1 and IgA2. The hinge region of IgA, which gives the immunoglobulin flexibility, is comprised of a series of amino acids, in IgA nephropathy, we have abnormal glycosylation of the hinge region, causing them to be galactose deficient. These galactose deficient antibodies are no longer recognised as self, so IgGs bind to the IgA1 forming immunecomplexes. These immune complexes then deposit in the kidney (a type III hypersensitivity reaction).
The galactose deficient IgA1s form the ‘first hit’ of a ‘two hit’ process, the second hit being an infection of the mucosal lining (where most IgAs are found). These infections cause increase in IgA1 production, leading to immune complex deposits in the glomerular mesangium.
Specifically, these immune complexes deposit in the mesangium of the glomeruli, this activates the alternative complement system, causing proinflammatory cytokine release and macrophage recruitment all leading to glomerular injury causing RBC and protein in urine (nephritic). This glomerular injury occurs each time there is a mucosal infection, over time we begin to see glomerular scarring and over decades, renal failure.
Clinical presentation of IgA nephropathy is often asymptomatic microscopic hematuria with or without proteinuria after an upper respiratory tract infection or exercise. 20-50% of patients have hypertension as well. Diagnosis is by finding IgA deposits under immunofluorescence
microscopy. Light microscopy shows anything from mild mesangial proliferation to severe crescentic glomerulonephritis.
Treatment is based on the following principles:
- Control of BP
- Antihypertensive medication and diet control
- Prevent immune complex formation
- Prednisolone (0.8mg/kg/day for 2 months tapered to 0.2mg/kg/day)