Mechanical challenges to the glomerulus and podocyte loss: evolution of a paradigm.

In this article, I shall outline some of the most important aspects of the evidentiary basis of the so-called Kriz model for the development of glomerular sclerosis, a model that we continue to modify to this day. In my mind, the most important findings include the fact that podocytes are generally post-mitotic cells, so that loss of a significant number for any cause leads to podocyte insufficiency. Another pivotal finding is that in many experimental models and in human disease, podocytes detach from the GBM as living cells. These facts, together with biomechanical deduction, have led to the ongoing evolution of the original Heidelberg model.