Distribution of endothelin immunoreactivity in human kidney correlates with antemortem acute renal failure: A possible postmortem immunohistochemical test

The role of endothelin in the normal kidney function, as well as in disease states, has been studied in animal models. In addition, it was shown previously that endothelial, mesangial, and epithelial components of the nephron produce endothelins, in particular ET-1. We performed immunohistochemistry for ET-1 reactivity on 31 autopsy and four surgically removed kidneys. Eighteen cases had clinical diagnoses of acute renal failure (ARF). In the remaining 17 cases with normal or unchanged renal function before death or surgery, ET-1 immunoreactivity was present in tubular epithelium, with the most intense staining in the medullary collecting tubules. In 13 of 18 cases of ARF, tubular staining was either replaced or accompanied by interstitial reactivity in the inner and outer medulla, corresponding to the location of the vasa recta and interlobular arteries identified by factor VIII immunostaining. Controlled autolysis performed on normal kidney over 72 hours postmortem produced tubular epithelial degradation with reduced epithelial cell endothelin reactivity, but not an interstitial pattern. In situ hybridization for ETmRNA localized expression to tubular and collecting duct epithelium in both normal and acute renal failure cases. The change in the localization of ET-1 immunoreactivity from tubular epithelium to the interstitium in these ARF cases does not appear to be the result of increased vascular endothelial production of endothelin. This altered immunoreactivity pattern for ET-1 may be a marker of antemortem tubular damage and can be used as an adjunct in the autopsy diagnosis of ARF.