Angiotensin-converting Enzyme Inhibitors in Chronic Renal Failure

In contrast to some other antihypertensive drugs, angiotensin-converting enzyme (ACE) inhibitors lower glomerular capillary pressure, decrease proteinuria, and may halt progressive glomerular injury and loss of renal function in experimental chronic renal failure (CRF). Although these favourable effects of ACE inhibition may result from alterations in glomerular haemodynamics, there is some evidence to show that ACE inhibitors may reduce glomerular injury through other mechanisms. CRF in man may result from a variety of insults to the kidney. However, it is not known whether, or under which conditions, glomerular capillary pressure is elevated in this heterogeneous population. Limited data suggest that renal haemodynamics (and perhaps glomerular capillary pressure) may depend in part on the level of systemic blood pressure. In addition, several studies have demonstrated a positive correlation between systemic blood pressure and the rate of progression of CRF. ACE inhibitor therapy generally lowers systemic blood pressure, does not alter renal function and decreases proteinuria in patients with CRF. The reduction in proteinuria appears to be variable and may depend on pretreatment glomerular haemodynamics and/or the activity of the renin-angiotensin-aldosterone system. Preliminary evidence also suggests that ACE inhibitors may slow the progression of renal disease in humans with CRF. However, this effect, like the reduction in proteinuria, has not been observed consistently in all patients. In addition, it is not clear whether these effects on proteinuria and progression of disease are unique to ACE inhibitor therapy, since the lowering of systemic blood pressure with other drugs may have similar effects. The heterogeneity of the response to ACE inhibition suggests that there may be interpatient differences in glomerular haemodynamics in CRF, perhaps related to systemic blood pressure or the underlying disease process. Studies to date indicate that ACE inhibitors exert their beneficial effect by lowering glomerular capillary pressure and that not all patients will benefit from therapy with regard to proteinuria or amelioration of disease progression. However, further investigation of the haemodynamic and non-haemodynamic effects of ACE inhibitors, as well as the variability of response, may ultimately allow the selection of those patients who would benefit from such therapy.