BOLD-MRI assessment of intrarenal oxygenation and oxidative stress in patients with chronic kidney allograft dysfunction.
Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) uses deoxyhemoglobin as an endogenous contrast agent for the noninvasive assessment of tissue oxygen bioavailability. We hypothesized that intrarenal oxygenation was impaired in patients with chronic allograft nephropathy (CAN). Ten kidney-transplant recipients with CAN and nine healthy volunteers underwent BOLD-MRI. Medullary R2* (MR2*) and cortical R2* (CR2*) levels (measures directly proportional to tissue deoxyhemoglobin levels) were determined alongside urine and serum markers of oxidative stress (OS): hydrogen peroxide (H(2)O(2)), F(2)-isoprostanes, total nitric oxide (NO), heat shock protein 27 (HSP27), and total antioxidant property (TAOP). Mean MR2* and CR2* levels were significantly decreased in CAN (increased local oxyhemoglobin concentration) compared with healthy volunteers (20.7 +/- 1.6 vs. 23.1 +/- 1.8/s, P = 0.03 and 15.9 +/- 1.9 vs. 13.6 +/- 2.3/s, P = 0.05, respectively). There was a significant increase in serum and urine levels of H(2)O(2) and serum HSP27 levels in patients with CAN. Conversely, urine NO levels and TAOP were significantly increased in healthy volunteers. Multiple linear regression analyses showed a significant association between MR2* and CR2* levels and serum/urine biomarkers of OS. BOLD-MRI demonstrated significant changes in medullary and cortical oxygen bioavailability in allografts with CAN. These correlated with serum/urine biomarkers of OS, suggesting an association between intrarenal oxygenation and OS.
Djamali
Arjang
A
Department of Medicine, University of Wisconsin-Madison, Madison, WI 53713, USA. axd@medicine.wisc.edu
Sadowski
Elizabeth A
EA
Muehrer
Rebecca J
RJ
Reese
Shannon
S
Smavatkul
Chanigan
C
Vidyasagar
Aparna
A
Fain
Sean B
SB
Lipscomb
Ryan C
RC
Hullett
Debra H
DH
Samaniego-Picota
Millie
M
Grist
Thomas M
TM
Becker
Bryan N
BN
D000328:Adult; D015415:Biomarkers; D028441:F2-Isoprostanes / Q000652:urine; D005260:Female; D006084:Graft Rejection / Q000503:physiopathology*; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007668:Kidney / Q000503:physiopathology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D019808:Losartan / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000097:blood*; D012964:Sodium / Q000652:urine
D015415:Biomarkers; D028441:F2-Isoprostanes; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D006454:Hemoglobins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D009569:Nitric Oxide; C100003:deoxyhemoglobin; D012964:Sodium; D006861:Hydrogen Peroxide; D019808:Losartan; D010100:Oxygen