title: Atherosclerotic renal artery stenosis is associated with elevated cell cycle arrest markers related to reduced renal blood flow and postcontrast hypoxia.
abstract: Atherosclerotic renal artery stenosis (ARAS) reduces renal blood flow (RBF), ultimately leading to kidney hypoxia and inflammation. Insulin-like growth factor binding protein-7 (IGFBP-7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) are biomarkers of cell cycle arrest, often increased in ischemic conditions and predictive of acute kidney injury (AKI). This study sought to examine the relationships between renal vein levels of IGFBP-7, TIMP-2, reductions in RBF and postcontrast hypoxia as measured by blood oxygen level-dependent (BOLD) magnetic resonance imaging.
  
  
  
  Renal vein levels of IGFBP-7 and TIMP-2 were obtained in an ARAS cohort (n= 29) scheduled for renal artery stenting and essential hypertensive (EH) healthy controls (n = 32). Cortical and medullary RBFs were measured by multidetector computed tomography (CT) immediately before renal artery stenting and 3 months later. BOLD imaging was performed before and 3 months after stenting in all patients, and a subgroup (N = 12) underwent repeat BOLD imaging 24 h after CT/stenting to examine postcontrast/procedure levels of hypoxia.
  
  
  
  Preintervention IGFBP-7 and TIMP-2 levels were elevated in ARAS compared with EH (18.5 ± 2.0 versus 15.7 ± 1.5 and 97.4 ± 23.1 versus 62.7 ± 9.2 ng/mL, respectively; P< 0.0001); baseline IGFBP-7 correlated inversely with hypoxia developing 24 h after contrast injection (r = -0.73, P< 0.0001) and with prestent cortical blood flow (r = -0.59, P= 0.004).
  
  
  
  These data demonstrate elevated IGFBP-7 and TIMP-2 levels in ARAS as a function of the degree of reduced RBF. Elevated baseline IGFBP-7 levels were associated with protection against postimaging hypoxia, consistent with 'ischemic preconditioning'. Despite contrast injection and stenting, AKI in these high-risk ARAS subjects with elevated IGFBP-7/TIMP-2 was rare and did not affect long-term kidney function.
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Saad
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
authors.forename: Sandra M S
authors.initials: SM
authors.lastname: Herrmann
authors.affiliation: Department of Interventional Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Glockner
authors.affiliation: Department of Interventional Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Mckusick
authors.affiliation: Department of Interventional Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Misra
authors.affiliation: Department of Interventional Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Haraldur
authors.initials: H
authors.lastname: Bjarnason
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Textor
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood*; D059447:Cell Cycle Checkpoints; D003287:Contrast Media / Q000009:adverse effects*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000139:chemically induced*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007668:Kidney / Q000098:blood supply / Q000000981:diagnostic imaging*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D061330:Multidetector Computed Tomography / Q000379:methods; D012078:Renal Artery Obstruction / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D012079:Renal Circulation / Q000502:physiology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood
chemical_list: D015415:Biomarkers; D003287:Contrast Media; D018969:Insulin-Like Growth Factor Binding Proteins; C560823:TIMP2 protein, human; C102529:insulin-like growth factor binding protein-related protein 1; D019716:Tissue Inhibitor of Metalloproteinase-2
keywords: contrast; ischemia; renal artery stenosis; revascularization; stent