IgA nephropathy treatment 25 years on: can we halt progression? The evidence base.

Berger’s disease, considered benign in the classic descriptions and for a decade, is perhaps the most challenging primary glomerulonephritis in which to evaluate pathogenesis, its impact on renal services and to discover effective treatments for progressive forms, yet these remain inchoate 25 years after the first trial constructs [1]. A wide variety of treatments has been attempted [2] and most facets of immune perturbations, blood rheology, glomerular inflammation and haemodynamics addressed. Three reasons suggest why we remain perplexed: (i) the timescale of progression of commoner forms (a decade or more) means studies have addressed parameters, notably proteinuria, rather than loss of glomerular filtration rate (GFR) using ‘soft’ end-points (those subject to haemodynamic variables modifying residual function); (ii) studies in a disease as heterogeneous merit careful design, incorporating probability modelling to address pivotal questions, most importantly, retarding progression ‘primum non nocere’ [3] ; and (iii) broad concepts of pathogenesis encompass a failure in immune system competence, to, in contrast, one analogous to systemic lupus erythematosus – these disparate views or perceptions that disease immune mechanisms resist abrogation, have broadened the approach to treatments.