The role of platelets in progressive glomerulosclerosis: mechanisms for intraglomerular platelet activation and pathogenetic consequences.

Purkerson et al. have hypothesized that platelet aggregation and release reactions contribute to the progressive sclerosis of remnant nephrons. The suggested mechanism for platelet activation is disruption of endothelium by the high hydraulic pressures characteristic of remnant nephrons, with platelet exposure to basement membrane collagen. We herein postulate additional mechanisms whereby platelets might be activated in the microcirculation of remnant nephrons: (i) kinetic activation due to high plasma flow rates; (ii) close cell contact due to concentration of blood cells and platelets in the glomerulus; (iii) concentration of protein macromolecules that act as agonists for platelet release; (iv) glomerular release of saturated and monenoic fatty acids that stimulate platelet synthesis of thromboxane A2; (v) glomerular release of membrane-bound pro-coagulant factor, triggering a chain reaction that activates both platelets and the intraglomerular coagulation cascade. Platelet activation could play a pathogenetic role in many of the known derangements of structure and function in remnant nephrons. This paradigm may also be partially applicable to the glomerulosclerosis of diabetes mellitus.