IgAN–Definition and Clinical Observations The original description of IgAN was made by patholo-gists [1]. The definition remains unchanged and is based on renal pathology: mesangial IgA in the presence of clinical disease typified by haematuria, overt or covert, in the absence of systemic illness, particularly lupus and liver disease. Episodic macroscopic haematuria is the archetypal clinical presentation typically coinciding with mucosal infection. The late stages of the disease with proteinuria, hypertension and histological evidence of glomerular and interstitial scarring have little to distinguish them from any progressive chronic glomerular disease. It is the early rather than the late stage of the disease which is unique to IgAN, and which needs study to understand the fundamental mechanisms behind glomerular IgA deposition. plgA and a Hypothesis for the Initiating Events in IgAN There is considerable evidence that polymeric forms of IgA may play a key role in IgAN. Not only is plgA deposited in the mesangium, plgA may be increased in the circulation and plgA production may be enhanced in in vitro lymphocyte culture systems. plgA is mostly syn-thesised in the mucosa, and mucosal infection is the typical precipitant of acute haematuria episodes in IgAN. These observations have together supported the following hypothesis for the immunopathogenesis of IgAN: