Urinary endothelin in renal disease. A, Urinary endothelin levels in patients with cyclosporine-induced renal dysfunction and hypertension before and after liver transplantation. These patients had near-normal kidney function before liver transplantation, after which their glomeru-lar filtration rates decreased from 85 to 55 mL/min, on average. These data underscore the observation that the kidney itself is a rich source of vasoactive materials and that renal excretion of substances such as endothelin is independent of circulating blood levels . Endothelin has properties that both facilitate vasoconstriction and enhance mitogenic and fibrogenic responses, perhaps accelerating interstitial fibrosis in the kidney. Early withdrawal of cyclosporine leads to reversal of a diminished glomerular filtration rate. With time, however, these changes lose the feature of reversibility . B, Renal ablation. Urinary endothelin levels in rats exposed to reduced renal mass achieved by 5/6 nephrectomy. As in humans, plasma levels of endothelin were dissociated from urinary levels, and injected endothelin was not excreted. These results suggest that urinary levels were of renal origin. These studies further support the concept that the diminished nephron number elicits production of potent vasoactive and inflammatory materials that may accelerate irreversible parenchy-mal injury. (Panel A from Textor and coworkers ; with permission. Data in panel B from Benigni and coworkers .)
Renal parenchymal disease
Decreased afferent resistance Decreased efferent resistance
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