Five hundred years of the nephrotic syndrome: 1484-1984

The nephrotic syndrome has emerged over several centuries as the consequence of continued profuse proteinuria, arising in turn from a variety of lesions affecting the glomerulus which impair glomerular ability to retain plasma proteins, in particular, albumin. As a syndrome, it has its own complications and requires its own management irrespective of the underlying lesions. Dissection of these by renal biopsy and by clinical investigation reveals a variety of systemic diseases which affect the kidney, but a majority of primary immune-based diseases appear unique to the glomerulus. Whether the lesion called by Müller and Munk ‘nephrosis’, and now called minimal change disease and focal segmental glomerulosclerosis is one disease or many, is the subject of intense debate at the moment, as is the relationship between two types of lesion. Only a better understanding of their pathogenesis, and of how the glomerulus normally retains plasma protein, will solve this knotty problem.