New Insight into Treatment of Diseases of Glomerular Endothelium

The capillary wall of the glomerulus, which is composed of glomerular endothelial cells (GECs), the glomerular basement membrane (GBM), and podocytes, is responsible for the ultrafi ltration of plasma in the kidney. The function of the fenestrated endothelium in fi ltration is poorly understood. On the other hand, the presence of a signifi cant glomerular endothelial glycocalyx implies that the glomerular endothelium signifi cantly contributes to the barrier to macromolecules. Vascular endothelial growth factor (VEGF) is the most important and tightly regulated angiogenic cytokine in the kidney. Studies of fenestration formation have relied on overexpression of VEGF in in vivo models or on in vitro systems where VEGF or pharmacological agents are added exogenously. A greater understanding of the glomerular endothelial cells relevance of in glomerular physiology and pathology naturally raises the question of whether it will be possible to manipulate them therapeutically. For example, promotion of fenestration formation would be desirable in severe preeclampsia to avoid renal failure and may increase GFR in a number of other conditions, including diabetic nephropathy. In the near future, the use of experimental methods will further expand understanding of the pathology of the glomerular fi ltration barrier, and perhaps reveal novel target molecules for the therapy of proteinuric kidney diseases.