[Therapeutic perspectives in primary glomerulonephritis from recent physiopathological data]

In this review the authors describe the physiopathological mechanisms responsible for inflammatory lesions in primary glomerulonephritis. Primary glomerular nephropathies can be reproduced experimentally: models have been set up for non-proliferative kidney diseases such as minimal change disease or membranous glomerulopathies, and for proliferative kidney diseases such as Berger's disease. Studies performed with these models have resulted in the identification of inflammatory mechanisms creating glomerular lesions which may be acute (proteinuria) or progressive (glomerular sclerosis). These mechanisms include activation of resident cells, notably mesangial cells, and recruitment of circulating cells such as neutrophils, monocytes/macrophages and platelets. These cells participate in the local inflammatory reaction by releasing soluble mediators including biologically active lipids, such as eicosanoids, reactive oxygen and nitrogen derivatives, proteases, cytokines and vasoactive polypeptides. The importance of these mediators has been deduced from the fact that they are produced locally in excess, their introduction produces lesions and, above all, their suppression by inhibitory or antagonistic pharmacological agents reduces the severity of the lesions. Several observations have shown that the development of all the lesions can be prevented simply by blocking the activity of only one of these mediators. It is therefore possible to consider replacing the conventional glucocorticoid treatment, which has multiple pharmacological actions, by a more specific treatment directed against a single mediator.