This investigation studies the toxicity of
heme proteins and/or their break-down products on renal function.
Heme proteinemia precedes acute tubule
necrosis at a frequency great enough to suggest a causal relationship between the two events. Physiological and metabolic functions of kidney slices are investigated in several models of acute tubule
necrosis. Organic
acid and organic base transport is depressed earliest. These alterations in tubule function cannot be explained by
ischemia or obstruction alone.
Heme proteinemia in rats or incubation of renal slices in medium containing
heme proteins yields several interesting observations. Neither in vivo or in vitro do
hemoglobin and
methemoglobin alone produce a depressive effect on the transport systems studied. However, parallel to many clinical situations, when such secondary insults as
hypoxia and elevated
ammonia concentrations are included in the experimental design, transport functions are depressed. Ferrihemate, a molecule smaller than
hemoglobin or
methemoglobin, depresses transport function without secondary insults. From these studies it is concluded that
heme proteins play a role in tubule dysfunction seen in acute tubule
necrosis. A model is presented that collates these data with other factors known to play a part in the pathogenesis of this renal syndrome.