The mesangium as a target for glomerulopathic light and heavy chains: pathogenic considerations in light and heavy chain-mediated glomerular damage.

Certain structurally abnormal light and heavy chains are known to be nephrotoxic and alter mesangial homeostasis producing pathological alterations. Many of the mechanisms involved in light chain-mesangial interactions have been deciphered using an in vitro model, providing a framework for understanding the sequence of events that leads to irreversible glomerular changes and eventually renal failure. The molecular events involved in the pathogenesis of these disorders are now for the most part well-established. These studies have delineated the sequence of steps involved and crucial events have been determined. An animal model is being developed which will undoubtedly contribute significantly to validate the information that has been obtained from the in vitro models. The present chapter will address the pathogenesis of these disorders with an emphasis on highlighting crucial steps possibly amenable to therapeutic intervention to stop or ameliorate adverse consequences leading to irreversible changes.