Prospects and Perspectives on IgA Nephropathy from Animal Models

The focus of this chapter is a systematic and critical review of the insights that experimental models have contributed to our understanding of IgA nephropathy (IgAN). We consider the generation of IgA subject to glomerular deposition, the partitioning of IgA between the circulation and glomeruli, the clearance of IgA and complexes containing IgA from the circulation, the 'upstream' effectors of glomerular pathophysiology, the inflammatory mediators that connect intraglomerular stimuli to functional and morphologic effects, and the contribution of animal models to our current understanding of the role that glycosylation of IgA plays in the genesis of IgAN. In each of these subsections, the evidence in favor of each principle or hypothesis is weighed in consideration of other potentially contradictory evidence and relevant issues related to IgAN in patients. The key limitations of each model system are presented, and where possible, reconciliation of discrepant observations are proposed. Subsequently, a synopsis of spontaneous models that do not offer particular mechanistic insights, and a compilation of experimental therapeutic initiatives, are reviewed. In all respects, the discussion of observations in patients or cells in vitro is limited to points where these data impinge upon interpretation of the data derived from the animal models.