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Pathophysiology of renal failure in renovascular disease
1Department of Medicine, Mayo Clinic, Rochester, MN 55905.
Abstract:
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.
Insights
Gradual reduction in renal perfusion pressure causes different kidney injuries than acute ischemia. Understanding chronic renal perfusion deficits is key for treating renovascular disease.
Area of Science:
- Nephrology
- Cardiovascular Physiology
- Renal Pathophysiology
Background:
- Renovascular compromise is increasingly recognized as a cause of chronic renal failure.
- The mechanisms by which kidneys near critical perfusion pressures sustain parenchymal injury are not fully understood.
Purpose of the Study:
- To investigate the distinct functional and morphological consequences of gradual versus acute reductions in renal perfusion pressure.
- To compare the effects of chronic antihypertensive therapy versus acute aortic ligation on renal hemodynamics and function.
Main Methods:
- Conscious rats underwent an aortic coarct model with antihypertensive therapy (sodium restriction, ACE inhibition) for 4 weeks.
- A separate group experienced acute reduction of renal pressures via total aortic ligation.
- Poststenotic renal pressures, glomerular volume, renal function, and urinary N-acetyl-glucosaminidase were measured.
Main Results:
- Both models reduced poststenotic pressures to 50-60 mm Hg.
- Acute aortic ligation caused tubular necrosis and glomerular collapse with markedly elevated urinary N-acetyl-glucosaminidase.
- ACE inhibition led to reduced renal blood flow and glomerular filtration rate but preserved tubular function.
Conclusions:
- Gradual reduction in renal perfusion pressure results in different functional and morphological changes compared to acute ischemic injury.
- Potential mechanisms for chronic injury include disrupted vascular regulation, energy metabolism, and cellular integrity.
- Further research into chronic renal parenchymal injury pathways is essential for effective human interventions.