title: Regional alterations in renal haemodynamics and oxygenation: a role in contrast medium-induced nephropathy.
abstract: Although the nature of renal dysfunction following the use of iodinated radiological contrast agents has long been a matter of dispute, tubular hypoxic injury does play a central role as indicated by both clinical observations and experimental animal models. Indeed, radiocontrast agents induce renal parenchymal hypoxic stress resulting from a critically low ambient pO2 that develops particularly in the renal medulla. This medullary oxygen insufficiency is a reflection of both increased oxygen consumption for solute reabsorption and a reduction of regional inner medullary blood flow. Cellular adaptation to hypoxia is mediated by hypoxia-induced transcription factors (HIFs), which are regulated by oxygen-dependent proteolysis. HIF action confers cell protection through a wide array of target genes, thus restricting tubular epithelial damage. Most clinical risk factors for contrast nephropathy are characterized by predisposition to medullary oxygen insufficiency (such as altered nitric oxide or prostaglandin synthesis, both vital in maintaining medullary oxygenation), by co-existing vasoconstrictive stimuli, by enhanced transport workload or by structurally altered microcirculation. Under such predisposing conditions, regional hypoxic stress may intensify and surpass the capacity for the generation of adaptive responses, evolving into apoptotic or necrotic tubular cell death, associated with renal dysfunction. Amelioration of medullary hypoxic stress should be taken into account when designing strategies to prevent or attenuate contrast media-induced nephropathy.
authors.affiliation: Department of Medicine, Hadassah University Hospital, Mount Scopus, PO Box 24035, Jerusalem 91240, Israel. heyman@cc.huji.ac.il
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Heyman
authors.forename: Christian
authors.initials: C
authors.lastname: Rosenberger
authors.forename: Seymour
authors.initials: S
authors.lastname: Rosen
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000009:adverse effects*; D006439:Hemodynamics; D006801:Humans; D000860:Hypoxia / Q000150:complications; D007674:Kidney Diseases / Q000139:chemically induced* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D007679:Kidney Medulla / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D012079:Renal Circulation
chemical_list: D003287:Contrast Media; D010100:Oxygen