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. 1970 Feb 28;131(3):443–460. doi: 10.1084/jem.131.3.443

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

Sheldon R Braun 1, Frederick R Weiss 1, Allen I Keller 1, J Richard Ciccone 1, Harry G Preuss 1
PMCID: PMC2138821  PMID: 5413325

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bunn H. F., Jandl J. H. Exchange of heme among hemoglobin molecules. Proc Natl Acad Sci U S A. 1966 Sep;56(3):974–978. doi: 10.1073/pnas.56.3.974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bywaters E. G., Beall D. Crush Injuries with Impairment of Renal Function. Br Med J. 1941 Mar 22;1(4185):427–432. doi: 10.1136/bmj.1.4185.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. CARROLL R., KOVACS K., TAPP E. THE PATHOGENESIS OF GLYCEROL-INDUCED RENAL TUBULAR NECROSIS. J Pathol Bacteriol. 1965 Apr;89:573–580. doi: 10.1002/path.1700890216. [DOI] [PubMed] [Google Scholar]
  4. CROSS R. J., TAGGART J. V. Renal tubular transport: accumulation of p-aminohippurate by rabbit kidney slices. Am J Physiol. 1950 Apr 1;161(1):181–190. doi: 10.1152/ajplegacy.1950.161.1.181. [DOI] [PubMed] [Google Scholar]
  5. FINCKH E. S. The indirect action of subcutaneous injections of glycerol on the renal tubules in the rat. J Pathol Bacteriol. 1959 Jul;78:197–202. [PubMed] [Google Scholar]
  6. GOLDBERG M. Studies of the acute renal effects of hemolyzed red blood cells in dogs including estimations of renal blood flow with krypton. J Clin Invest. 1962 Dec;41:2112–2122. doi: 10.1172/JCI104669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jaenike J. R. The renal lesion associated with hemoglobinemia: a study of the pathogenesis of the excretory defect in the rat. J Clin Invest. 1967 Mar;46(3):378–387. doi: 10.1172/JCI105539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. KOISHI T. Studies on renal tubular transport. I. Accumulation of p-aminohippurate by kidney slices. Jpn J Pharmacol. 1959 Mar;8:101–123. doi: 10.1254/jjp.8.101. [DOI] [PubMed] [Google Scholar]
  9. KREBS H. A., BENNETT D. A., DE GASQUET P., GASQUET P., GASCOYNE T., YOSHIDA T. Renal gluconeogenesis. The effect of diet on the gluconeogenic capacity of rat-kidney-cortex slices. Biochem J. 1963 Jan;86:22–27. doi: 10.1042/bj0860022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. LALICH J. J. The influence of in vitro hemoglobin modification on hemoglobinuric nephrosis in rabbits. J Lab Clin Med. 1952 Jul;40(1):102–110. [PubMed] [Google Scholar]
  11. LALICH J. J. The role of brown pigment in experimental hemoglobinuric nephrosis. AMA Arch Pathol. 1955 Oct;60(4):387–392. [PubMed] [Google Scholar]
  12. LALICH J. J. The rôle of oxyhemoglobin and its derivatives in the pathogenesis of experimental hemoglobinuric nephrosis. Am J Pathol. 1955 Jan-Feb;31(1):153–165. [PMC free article] [PubMed] [Google Scholar]
  13. Preuss H. G., Bise B. B., Schreiner G. E. The determination of glutamine in plasma and urine. Clin Chem. 1966 Jun;12(6):329–337. [PubMed] [Google Scholar]
  14. Preuss H. G., Murdaugh H. V. The toxic effect of ammonia on renal cortical tubule function in vitro. J Lab Clin Med. 1968 Apr;71(4):561–572. [PubMed] [Google Scholar]
  15. ROSOFF C. B., WALTER C. W. The controlled laboratory production of hemoglobinuric nephrosis. Ann Surg. 1952 Mar;135(3):324–331. doi: 10.1097/00000658-195203000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Thiel G., Wilson D. R., Arce M. L., Oken D. E. Glycerol induced hemoglobinuric acute renal failure in the rat. II. The experimental model, predisposing factors, and pathophysiologic features. Nephron. 1967;4(5):276–297. doi: 10.1159/000179588. [DOI] [PubMed] [Google Scholar]

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