Pathophysiology of Renal Failure in Renovascular Disease

Recent attention has focused on renovascular compromise as a cause of chronic renal failure. The sequence by which kidneys functioning near the limits of “critical perfusion pressures” develop parenchymal injury is not well understood. We studied poststenotic renal pressures, glomerular volume, and renal function in conscious rats using an aortic coarct model during antihypertensive therapy with sodium restriction and angiotensin-converting enzyme inhibition over 4 weeks. These were compared with acute reduction of renal pressures using aortic ligation. Both models reduced poststenotic pressures to 50 to 60 mm Hg. Total aortic ligation produced tubular necrosis and glomerular collapse with 40-fold elevated urinary N-acetyl-glucosaminidase excretion. In contrast, angiotensin-converting enzyme inhibition reduced renal blood flow by 30% without evident disruption in tubular function, reflected by low fractional excretion of sodium levels and normal excretion of N-acetyl-glucosaminidase. The glomerular filtration rate and filtration fraction were reduced. These results indicate that gradual reduction of renal perfusion pressure produces functional and morphologic consequences different from those observed with acute ischemic injury. Mechanisms by which chronic renal perfusion deficits produce tissue injury are reviewed and may include disruption of vascular regulation, energy storage molecules, cellular ion gradients, free radical generation, and disruption of cytoskeletal configuration and repair mechanisms. Further study of the pathways of chronic renal parenchymal injury beyond arterial stenosis is essential to achieve rational intervention and revascularization in humans.