Is a legacy effect possible in IgA nephropathy?

Abstract

The term 'legacy effect'--a memory of a treatment which produces benefits long after the cessation of the intervention--was adopted for the first time to describe the benefits of early and strict control of diabetes on cardiovascular complications. The search for a similar effect for early treatment of immune-mediated renal diseases, interrupting some self-amplification loops of the pathogenetical immunological mechanisms and leaving a permanent memory, is fascinating. Some recent reports suggest a long-term beneficial or legacy effect of early treatment of IgA nephropathy after a randomized controlled trial (RCT) using mycophenolate mofetil, methylprednisolone pulses or steroid/immunosuppressive multiple therapy, or prolonged steroid doses associated with tonsillectomy. Long-lasting effects of treatments are more likely to be achieved in early stages of IgA nephropathy, when mesangial proliferative or endocapillary hypercellular lesions are pre-eminent over sclerosis, and when proteinuria is not massive, above all in young patients. The long-term results considered are relevant, but have the counterpart of the risk of drug toxicity or side effects, which are particularly undesired in patients with a mild disease. Hence, there is interest for drugs targeting the intestinal mucosal immunity with a little systemic effect, aimed at interrupting the initial pathogenetical mechanism. The possibility of modulating anti-inflammatory regulatory T cells by modifying inducible enzymes is another fascinating field of future research.