HEMODYNAMIC MODULATIONS IN IGA NEPHROPATHY

While a variety of immunologic factors are likely to be involved in th e initial acute phlogistic events in IgA nephropathy (IgAN), progressi on to renal failure occurs through a relatively silent course histolog ically related to prevalent sclerotic changes. In this phase of IgAN, haemodynamic mechanisms are likely to play the most important role. Am ong the others, angiotensin II and endothelin 1 are thought to be crit ical mediators. Angiotensin II promotes mesangial cell contraction, mo dulates membrane permselectivity and induces glomerular hypertension. Evidence for a local angiotensin II hyperactivity in IgAN (especially in patients at definite risk of progression) has been previously provi ded by our group. Endothelin 1 is mitogenetic for mesangial cells and increases matrix production. Moreover, it exerts local vasoconstrictor effects and induces mesangial cell contraction, both resulting in glo merular afterload. Again, plasma and urinary endothelin 1 are elevated in IgAN. Moreover, those patients with increased risk of progression show an increased ratio between urinary endothelin 1 and cyclic guanos ine 3',5' monophosphate (GMP), a local messanger with counterbalancing effects. Several data of clinical benefits of angiotensin-converting enzyme inhibitors in IgAN have been reported. Less is known about the intrinsic mechanism of the antiproteinuric action, either reduction of filtration fraction or changes in glomerular permselectivity. The cli nical usefulness of factors counterbalancing endothelin 1 effects, suc h as nitric oxide donors, remains to be established. A sample of eight IgAN patients with poor prognostic indicators was enrolled to examine the renal haemodynamic effects of angiotensin receptor antagonism, an giotensin-converting enzyme inhibition and administration of an exogen ous source of nitric oxide. Study periods (7 days each) were randomize d and spaced out by one week wash-out. Data showed that angiotensin re ceptor antagonism and angiotensin-converting enzyme inhibition were eq ually effective in modifying renal haemodynamics, but only the latter condition significantly reduced albuminuria, possibly indicating a pre valent action on membrane permselectivity in the short time period of the study. The antiproteinuric effects of nitric oxide donors were str ictly confined to patients with increased urinary endothelin 1/cyclic GMP ratio. Finally, each treatment condition was found to be associate d with an increased nitric oxide production, which appeared to be an a dditional factor in modulation of filtration fraction changes.