DO GLOMERULAR ATHEROSCLEROSIS AND LIPID-MEDIATED TUBULOINTERSTITIAL DISEASE CAUSE PROGRESSIVE RENAL-FAILURE IN MAN

The nephrotic syndrome presents the kidney with a new environment in w hich blood vessels, glomerular structures and tubules are exposed over substantial periods of time to lipoproteins. LDL has charge affinity with glomerular basement membrane glycosaminoglycans, so potentially i ncreases or maintains albumin loss. This in turn stimulates LDL synthe sis. HDL is small enough to be passed by the glomerular filter in subs tantial amounts and has been found to stimulate endothelin-1 productio n by human proximal tubular cells in culture. LDL also inhibits nitric oxide vasodilatory responses, an action which when added to that of e ndothelin-1 may result in decreased renal tissue oxygenation. Taken to gether, these aspects of the nephrotic syndrome broaden conventional d efinitions of atherosclerosis and offer a number of targets for therap y in progressive renal disease.