PAI-1 as a target in kidney disease.

Fibrotic renal diseases represent a major health care problem because of their prevalence and the fact that available therapies merely slow, but do not halt progression to renal failure. New therapies to further slow or stop the progression to end stage of renal disease (ESRD) are urgently needed. PAI-1 has emerged as a powerful fibrogenic molecule in kidney disease and its overexpression has effects beyond its role in regulating the fibrinolytic system. PAI-1's ability to inhibit plasmin-dependent extracellular matrix turnover, to stimulate infiltration of macrophages and myofibroblasts and to signal directly to regulate transforming growth factor-beta 1 expression, provide possible mechanistic pathways involved in progression of chronic kidney disease. Blockade of PAI-1 represents a new and promising therapeutic approach that may help combat the current epidemic in chronic kidney disease.