title: Stent revascularization restores cortical blood flow and reverses tissue hypoxia in atherosclerotic renal artery stenosis but fails to reverse inflammatory pathways or glomerular filtration rate.
abstract: BACKGROUND
  Atherosclerotic renal artery stenosis (ARAS) is known to reduce renal blood flow, glomerular filtration rate (GFR) and amplify kidney hypoxia, but the relationships between these factors and tubulointerstitial injury in the poststenotic kidney are poorly understood. The purpose of this study was to examine the effect of renal revascularization in ARAS on renal tissue hypoxia and renal injury.
  
  
  RESULTS
  Inpatient studies were performed in patients with ARAS (n=17; >60% occlusion) before and 3 months after stent revascularization, or in patients with essential hypertension (n=32), during fixed Na(+) intake and angiotensin converting enzyme/angiotensin receptors blockers Rx. Single kidney cortical, medullary perfusion, and renal blood flow were measured using multidetector computed tomography, and GFR by iothalamate clearance. Tissue deoxyhemoglobin levels (R(2)*) were measured by blood oxygen level-dependent MRI at 3T, as was fractional kidney hypoxia (percentage of axial area with R(2)*>30/s). In addition, we measured renal vein levels of neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and tumor necrosis factor-α. Pre-stent single kidney renal blood flow, perfusion, and GFR were reduced in the poststenotic kidney. Renal vein neutrophil gelatinase-associated lipocalin, tumor necrosis factor-α, monocyte chemoattractant protein-1, and fractional hypoxia were higher in untreated ARAS than in essential hypertension. After stent revascularization, fractional hypoxia fell (P<0.002) with increased cortical perfusion and blood flow, whereas GFR and neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and tumor necrosis factor-α remained unchanged.
  
  
  CONCLUSIONS
  These data demonstrate that despite reversal of renal hypoxia and partial restoration of renal blood flow after revascularization, inflammatory cytokines and injury biomarkers remained elevated and GFR failed to recover in ARAS. Restoration of vessel patency alone failed to reverse tubulointerstitial damage and partly explains the limited clinical benefit of renal stenting. These results identify potential therapeutic targets for recovery of kidney function in renovascular disease.
authors.affiliation: Division of Nephrology and Hypertension, and Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Saad
authors.forename: Sandra M S
authors.initials: SM
authors.lastname: Herrmann
authors.forename: John
authors.initials: J
authors.lastname: Crane
authors.forename: James F
authors.initials: JF
authors.lastname: Glockner
authors.forename: Michael A
authors.initials: MA
authors.lastname: McKusick
authors.forename: Sanjay
authors.initials: S
authors.lastname: Misra
authors.forename: Alfonso
authors.initials: A
authors.lastname: Eirin
authors.forename: Behzad
authors.initials: B
authors.lastname: Ebrahimi
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Textor
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology / Q000628:therapy*; D007672:Kidney Cortex / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism*; D012078:Renal Artery Obstruction / Q000503:physiopathology / Q000628:therapy*; D012079:Renal Circulation; D015607:Stents
chemical_list: D010100:Oxygen
keywords: anoxia; hypertension; renal artery obstruction; revascularization
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