title: BOLD-MRI for the assessment of renal oxygenation in humans: acute effect of nephrotoxic xenobiotics.
abstract: Hypoxia of renal medulla is a key factor implicated in the development of drug-induced renal failure. Drugs are known to influence renal hemodynamics and, subsequently, affect renal tissue oxygenation. Changes in renal oxygenation can be assessed non-invasively in humans using blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI). This study was designed to test the acute effects of administration of specific drugs in healthy human kidney oxygenation using BOLD-MRI. Acute changes in renal tissue oxygenation induced by the non-steroidal anti-inflammatory drug indomethacin, the iodinated radio-contrast media (RCM) iopromidum, and the calcineurin inhibitors cyclosporine micro-emulsion (CsA-ME) and tracrolimus were studied in 30 healthy volunteers. A modified Multi Echo Data Image Combination sequence was used to acquire 12 T(2)(*)-weighted images. Four coronal slices were selected to cover both kidneys. The mean R(2)(*) (1/T(2)(*)) values determined in medulla and cortex showed no significant changes induced by indomethacin and tacrolimus administration. CsA-ME decreased medullary (P=0.008) and cortical (P=0.004) R(2)(*) values 2 h after ingestion. Iopromidum caused a significant increase in medullary R(2)(*) within the first 20 min after injection (P<0.001), whereas no relevant changes were observed in renal cortex. None of the measurements showed left-right kidney differences. Significant differences in renal medullary oxygenation were evidenced between female and male subjects (P=0.013). BOLD-MRI was efficient to show effects of specific drugs in healthy renal tissue. Cyclosporine increased renal medullary oxygenation 2 h after ingestion of a single dose, whereas indomethacin and tacrolimus showed no effect on renal oxygenation. Injection of iodinated RCM decreased renal medullary oxygenation.
authors.affiliation: Departement of Nephrology/Hypertension, University and Inselspital, Berne, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Hofmann
authors.forename: S
authors.initials: S
authors.lastname: Simon-Zoula
authors.forename: A
authors.initials: A
authors.lastname: Nowak
authors.forename: A
authors.initials: A
authors.lastname: Giger
authors.forename: P
authors.initials: P
authors.lastname: Vock
authors.forename: C
authors.initials: C
authors.lastname: Boesch
authors.forename: F J
authors.initials: FJ
authors.lastname: Frey
authors.forename: B
authors.initials: B
authors.lastname: Vogt
mesh_terms: D000293:Adolescent; D000328:Adult; D019069:Cell Respiration / Q000187:drug effects; D005260:Female; D006801:Humans; D007679:Kidney Medulla / Q000098:blood supply* / Q000187:drug effects*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption / Q000187:drug effects; D015262:Xenobiotics / Q000008:administration & dosage* / Q000633:toxicity
chemical_list: D015262:Xenobiotics; D010100:Oxygen