Abstract
IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world among patients undergoing renal biopsy. Approximately 30% of patients with IgAN develop end-stage kidney disease 20 years after renal biopsy. It is a glomerulopathy with a very broad clinical presentation, making it difficult to stratify and treat. IgAN is characterized by dysregulation of the immune system, which causes an abnormal synthesis of IgA1 that is deglycosylated causing its mesangial deposition. IgAN pathogenesis is incompletely understood; the current multi-hit hypothesis of IgAN pathogenesis does not explain the range of glomerular inflammation and renal injury associated with mesangial IgA deposition. Although associations between IgAN and glomerular and circulating markers of complement activation are established, the mechanism of complement activation and contribution to glomerular inflammation and injury are not defined. On the other hand, the renal-gut connection can also play an important role in the pathogenesis of IgAN with possible therapeutic implications. In order to standardize the histological findings, the Oxford Classification has allowed clarifying renal lesions that confer potential risk of progression. Currently, except for the blockade of the renin-angiotensin-aldosterone system, no other therapies are available in clinical setting for the treatment of IgAN, although the range of new drugs under investigation is extensive. The incorporation in the next trials of clinical parameters such as the amount of hematuria and histological lesions may allow more personalized therapeutic approaches. To summarize, in recent years, several important efforts have taken place in the understanding of IgAN, but still, further studies are warranted to elucidate the best therapeutic strategies according to the risk to improve the prognosis of this entity.
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