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| IgA nephropathy |
Pathogenesis
A cause of IgA nephropathy is the mesangial deposition of underglycosylated polymeric IgA type 1 in IgA-containing immune complexes. Polymeric IgA1 is produced by cells of mucosal origin that are produced to antigens presented at different mucosal surfaces. Infections in the respiratory or gastrointestinal (GI) tract with a triggered mucosal immune reaction are commonly associated with IgA nephropathy, implicating these mucosal systems in the pathogenesis of the disease. Underglycosylated polymeric IgA1 is normally secreted by plasma cells, derived from antigen primed mucosal B cells, into the lumen of the gastrointestinal or respiratory systems as part of the immune defence of these tissues. However, there is evidence to suggest that in the case of IgA nephropathy patients, B cells primed at mucosal sites mis-home to the bone-marrow, and as plasma cell secrete underglycosylated polymeric IgA1 into the bloodstream. In the bloodstream, it is proposed that the polymeric IgA1 form complexes that are susceptible to autoimmune attack, which is turn results in very large complexes that deposit in the kidney mesangium triggering kidney inflammation. Prolonged kidney inflammation causes a cascade of events leading to scarring and fibrosis and subsequent loss of renal function. The intestinal mucosa is the greatest source of underglycosylated polymeric IgA1.
Risk of Progression
Patients with IgA nephropathy can be divided into two categories, those not at risk and those at risk of progressing to ESRD.
Patients not at risk of progressing to renal failure
- Sporadic episodes of macroscopic haematuria (blood in urine giving tea-coloured appearance) and possibly proteinuria (protein in urine) that may coincide with infections of the upper respiratory tract, or less often gastroenteritis.
- No treatment is required, although clinicians are recommended to observe the patient on a regular basis.
Patients at risk of progressing to renal failure
- Patients presenting with persistent proteinuria, which may be accompanied by hypertension and loss of renal function. These three factors are strongly associated with increased risk of progression to renal failure.
- Treatment is necessary.
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