PROGRESSION OF GLOMERULAR-DISEASES - IS THE PODOCYTE THE CULPRIT

The stereotyped development of the glomerular lesions in many animal m odels and human forms of progressive renal disease suggests that there are common mechanisms of disease progression. We propose the outline of such a mechanism based on following aspects: (1) The glomerulus is a complex structure, the stability of which depends on the cooperative function of the basement membrane, mesangial cells and podocytes, cou nteracting the distending forces originating from the high glomerular hydrostatic pressures. Failure of this system leads to quite uniform a rchitectural lesions. (2) There is strong evidence that the podocyte i s incapable of regenerative replication post-natally; when podocytes a re lost for any reason they cannot be replaced by new cells. Loss of p odocytes may therefore lead to areas of ''bare'' GEM, which represent potential starting points for irreversible glomerular injury. (3) Atta chment of parietal epithelial cells to bare GEM invariably occurs when bare GEM coexists with architechtural lesions, leading to the formati on of a tuft adhesion to Bowman's capsule, the first ''committed'' les ion progressing to segmental sclerosis. (4) Within an adhesion the tuf t merges with the interstitium, allowing filtration from perfused capi llaries inside the adhesion towards the interstitium. The relevance of such filtration is as yet unclear but may play a considerable role in progression to global sclerosis and interstitial fibrosis.