PATHOGENESIS OF ACUTE-RENAL-FAILURE - NEW ASPECTS

Based on 2 case presentations - acute renal failure (ARF) due to myelo ma kidney and due to angiotensin-converting enzyme inhibitor administr ation in the presence of transplant artery stenosis - new aspects in t he pathogenesis of ARF are presented and discussed, The multifactorial pathogenesis of ARF includes (a) a disturbance of glomerular microcir culation (afferent and perhaps mesangial constriction, inadequate effe rent dilatation): (b) a disturbance of medullary microcirculation (med ullary capillary congestion) attributed to a combination of endothelia l damage and tubular dilatation; (c) tubular cell damage which, though rarely in humans justifying the term 'acute tubular necrosis', promot es both backleak of glomerular filtrate and shedding of brush border v esicles; (d) the latter promotes tubular obstruction by casts which co nsist of Tamm-Horsfall protein and brush border components, Once ARF i s established, repair processes set in which appear to depend on growt h factors such as epidermal growth factor and insulin-like growth fact or 1, of which there is a relative shortage in established ARF. Experi mental therapeutic approaches focus on the restitution of microcircula tion (endothelin receptor antagonists, atriopeptins), interference wit h cast formation (integrin receptor blockers), and the promotion of re covery by growth factors.