ANGIOTENSIN-CONVERTING ENZYME-INHIBITION AND RENAL PROTECTION - AN ASSESSMENT OF IMPLICATIONS FOR THERAPY

The role of hypertension in the pathogenesis of renal damage is a subj ect of both historical interest and current investigation. Because of the difficulty associated with studying the pathophysiologic role of g lomerular injury in systemic hypertension, experimental models have pr ovided much of the data in this field. The mechanisms leading to glome rular injury are complex and not fully elucidated. Mesangial and endot helial cell injury are thought to be important pathophysiologic mechan isms in the renal injury associated with hypertension. One hypothesis suggests that glomerular hypertension (ie, a hemodynamic event) is the primary pathogenetic mechanism, but another supports the notion that glomerular hypertrophy (ie, abnormal growth-related events) contribute s to injury. The intrarenal renin-angiotensin system may play an impor tant pathogenetic role in end-stage renal disease. Angiotensin-convert ing enzyme (ACE) inhibition has been shown to arrest the progression o f renal injury in animal models. Although the clinical database is inc omplete, the findings of anecdotal reports and short-term studies sugg est that ACE inhibition may preserve renal function in patients with s cleroderma renal crisis, reduce proteinuria in patients with diabetic nephropathy, and normalize renal hemodynamics in patients with a varie ty of renal diseases. The beneficial effects of ACE inhibition may be due to both hemodynamic (eg, reduction in glomerular capillary and int raglomerular pressures) and nonhemodynamic (eg, potassium-sparing and reduction in mesangial proliferation) mechanisms. The precise role of ACE inhibitors in the prevention of renal damage awaits the results of ongoing long-term, double-blind clinical studies. Nevertheless, ACE i nhibition may be an appropriate therapeutic alternative in the hyperte nsive patient whose renal injury is progressing despite aggressive ant ihypertensive therapy.