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Particular physicochemical characteristics of these light chains are responsible for their ability to alter mesangial milieu leading to glomerular damage. An <jats:italic>in vitro<\/jats:italic> model has been used to dissect the processes involved. This model has been instrumental in providing a solid platform from which to observe in a dynamic fashion how mesangial cells handle pathogenic light chains and the sequential steps that are involved in the progressive glomerular damage. Key steps amenable to possible modulation have been defined and should provide a solid platform to design and test therapeutic interventions. In the past significant difficulties have been encountered in the development of animal models of light chain\u2010induced glomerular damage. However, in the last few years a new generation of animal models has emerged to address whether what has been documented <jats:italic>in vitro<\/jats:italic> retains significance <jats:italic>in vivo<\/jats:italic>. 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