Preservation of glomerular filtration rate in human heart failure by activation of the renin-angiotensin system

When renal perfusion pressure is reduced in experimentally induced low-output states, glomerular filtration rate is preserved by angiotensin II-mediated efferent arteriolar vasoconstriction, but available evidence in man suggests that angiotensin II supports renal function only to the extent that it preserves systemic blood pressure. We performed simultaneous assessments of cardiac and renal function in 56 patients with severe chronic heart failure before and after 1 to 3 months of converting-enzyme inhibition. Among the 29 patients with a pretreatment renal perfusion pressure under 70 mm Hg, patients with preserved renal function (creatinine clearance > 50 ml/min/1.73 m²) had markedly elevated values for plasma renin activity (11.8 ± 3.8 ng/ml/hr) and showed a significant decline in creatinine clearance after converting-enzyme inhibition (61.1 ± 3.0 to 45.9 ± 5.3 ml/min/1.73 m²; p < .05). In contrast, although similar with respect to all pretreatment demographic, hemodynamic, and clinical variables, patients with a creatinine clearance under 50 ml/min/1.73 m² had low values for plasma renin activity (3.4 ± 0.8 ng/ml/hr) and, despite similar drug-induced decreases in systemic blood pressure, showed no change in creatinine clearance after therapy with captopril or enalapril (32.6 ± 2.5 to 41.4 ± 3.8 ml/min/1.73 m²). Changes in creatinine clearance varied linearly and inversely with pretreatment values for plasma renin activity (r = -.64, p < .001); converting-enzyme inhibition effectively abolished the pretreatment difference in renal function seen in the high- and low-renin subgroups. In the 27 patients with a renal perfusion pressure of 70 mm Hg or greater, creatinine clearance did not vary significantly with plasma renin activity and was not altered by therapy. These data indicate that the renin-angiotensin system plays an important role in preserving glomerular filtration rate in patients with congestive heart failure in whom renal perfusion pressure is severely compromised and that this effect is achieved independently of the ability of this hormonal system to support systemic blood pressure.