Towards a personalized treatment for IgA nephropathy considering pathology and pathogenesis

The search of personalized treatment for a subject with immunoglobulin A nephropathy (IgAN) is appealing since the individual long-term outcome is highly variable in spite of common mild clinical signs such as microscopic haematuria, moderate proteinuria and slightly reduced glomerular filtration rate (GFR). The only risk factor considered by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines to target corticosteroid/immunosuppressive treatment in IgAN is proteinuria persistently >1 g/day despite 3-6 months of optimized supportive care. However, proteinuria in IgAN may result not only from active lesions but also from sclerotic glomerular lesions with hyperfiltration and tubular damage. The Oxford classification study and subsequent investigations have indicated the value of pathology risk factors for progression independent of proteinuria, blood pressure and GFR at renal biopsy. Meanwhile new studies have provided an improved understanding of the pathogenetic mechanisms operating in IgAN leading to kidney tissue damage. These findings suggest the possibility for the individual patient with IgAN of using a pathology-based therapy, taking into consideration the pathogenetic mechanisms operating at the time of renal biopsy. This review is largely opinion based, since evidence-based reports are mostly incomplete: hypotheses are suggested based on interesting published investigations. The clinician faces a daily challenge: find the best management for his/her patient, modelling a rather general indication as obtained by the guidelines to the needs of the patient. This review offers some considerations that hopefully will be useful in this difficult choice.