EVALUATION OF THE RENAL TOXICITY OF HEME PROTEINS AND THEIR DERIVATIVES: A ROLE IN THE GENESIS OF ACUTE TUBULE NECROSIS

doi:10.1084/jem.131.3.443

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ARTICLE

EVALUATION OF THE RENAL TOXICITY OF HEME PROTEINS AND THEIR DERIVATIVES: A ROLE IN THE GENESIS OF ACUTE TUBULE NECROSIS

Sheldon R. Braun M.D.¹, Frederick R. Weiss M.D.¹, Allen I. Keller ¹, J. Richard Ciccone M.D.¹, and Harry G. Preuss M.D.¹

¹ From the Renal Metabolism Laboratory, Renal and Electrolyte Division, Department of Medicine of the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213

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

Submitted on August 25, 1969

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