DOI QR코드

DOI QR Code

Evaluation of Renal Pathophysiological Processes Induced by an Iodinated Contrast Agent in a Diabetic Rabbit Model Using Intravoxel Incoherent Motion and Blood Oxygenation Level-Dependent Magnetic Resonance Imaging

  • Yongfang Wang (Department of Radiology, First Hospital of China Medical University) ;
  • Xin Zhang (Department of Radiology, First Hospital of China Medical University) ;
  • Bin Wang (Department of Radiology, First Hospital of Shanxi Medical University) ;
  • Yang Xie (Department of Radiology, First Hospital of China Medical University) ;
  • Yi Wang (Department of Radiology, The Qianfoshan Hospital of Shandong Province) ;
  • Xuan Jiang (Cardiac Surgery, First Hospital of China Medical University) ;
  • Rongjia Wang (Department of Radiology, First Hospital of China Medical University) ;
  • Ke Ren (Department of Radiology, First Hospital of China Medical University)
  • Received : 2018.10.29
  • Accepted : 2019.01.03
  • Published : 2019.05.01

Abstract

Objective: To examine the potential of intravoxel incoherent motion (IVIM) and blood oxygen level-dependent (BOLD) magnetic resonance imaging for detecting renal changes after iodinated contrast-induced acute kidney injury (CI-AKI) development in a diabetic rabbit model. Materials and Methods: Sixty-two rabbits were randomized into 2 groups: diabetic rabbits with the contrast agent (DCA) and healthy rabbits with the contrast agent (NCA). In each group, 6 rabbits underwent IVIM and BOLD imaging at 1 hour, 1 day, 2 days, 3 days, and 4 days after an iohexol injection while 5 rabbits were selected to undergo blood and histological examinations at these specific time points. Iohexol was administrated at a dose of 2.5 g I/kg of body weight. Further, the apparent transverse relaxation rate (R2*), average pure molecular diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) were calculated. Results: The D and f values of the renal cortex (CO) and outer medulla (OM) were significantly decreased compared to baseline values in the 2 groups 1 day after the iohexol injection (p < 0.05). A marked reduction in the D* values for both the CO and OM was also observed after 1 hour in each group (p < 0.05). In the OM, a persistent elevation of the R2* was detected for 4 days in the DCA group (p < 0.05). Histopathological changes were prominent, and the pathological features of CI-AKI aggravated in the DCA group until day 4. The D, f, and R2* values significantly correlated with the histological damage scores, hypoxia-inducible transcription factor-1α expression scores, and serum creatinine levels. Conclusion: A combination of IVIM and BOLD imaging may serve as a noninvasive method for detecting and monitoring CI-AKI in the early stages in the diabetic kidney.

Keywords

Acknowledgement

The authors thank GuiboYu for technical assistance (Key Laboratory of Imaging Diagnosis and Interventional Radiology of Liaoning Province, Shenyang, Liaoning, China).

References

  1. McCullough PA. Contrast-induced acute kidney injury. J Am Coll Cardiol 2008;51:1419-1428 
  2. Li LP, Lu J, Zhou Y, Papadopoulou MV, Franklin T, Bokhary U, et al. Evaluation of intrarenal oxygenation in iodinated contrast-induced acute kidney injury-susceptible rats by blood oxygen level-dependent magnetic resonance imaging. Invest Radiol 2014;49:403-410 
  3. Calvin AD, Misra S, Pflueger A. Contrast-induced acute kidney injury and diabetic nephropathy. Nat Rev Nephrol 2010;6:679-688 
  4. Stacul F, van der Molen AJ, Reimer P, Webb JA, Thomsen HS, Morcos SK, et al.; Contrast Media Safety Committee of European Society of Urogenital Radiology (ESUR). Contrast induced nephropathy: updated ESUR Contrast Media Safety Committee guidelines. Eur Radiol 2011;21:2527-2541 
  5. Chalikias G, Drosos I, Tziakas DN. Contrast-induced acute kidney injury: an update. Cardiovasc Drugs Ther 2016;30:215-228 
  6. Kurnik BR, Allgren RL, Genter FC, Solomon RJ, Bates ER, Weisberg LS. Prospective study of atrial natriuretic peptide for the prevention of radiocontrast-induced nephropathy. Am J Kidney Dis 1998;31:674-680 
  7. Su J, Zou W, Cai W, Chen X, Wang F, Li S, et al. Atorvastatin ameliorates contrast medium-induced renal tubular cell apoptosis in diabetic rats via suppression of rho-kinase pathway. Eur J Pharmacol 2014;723:15-22 
  8. Li LP, Lu J, Franklin T, Zhou Y, Solomon R, Prasad PV. Effect of iodinated contrast medium in diabetic rat kidneys as evaluated by blood-oxygenation-level-dependent magnetic resonance imaging and urinary neutrophil gelatinase-associated lipocalin. Invest Radiol 2015;50:392-396 
  9. Inoue T, Kozawa E, Okada H, Inukai K, Watanabe S, Kikuta T, et al. Noninvasive evaluation of kidney hypoxia and fibrosis using magnetic resonance imaging. J Am Soc Nephrol 2011;22:1429-1434 
  10. dos Santos EA, Li LP, Ji L, Prasad PV. Early changes with diabetes in renal medullary hemodynamics as evaluated by fiberoptic probes and BOLD magnetic resonance imaging. Invest Radiol 2007;42:157-162 
  11. Hueper K, Hartung D, Gutberlet M, Gueler F, Sann H, Husen B, et al. Assessment of impaired vascular reactivity in a rat model of diabetic nephropathy: effect of nitric oxide synthesis inhibition on intrarenal diffusion and oxygenation measured by magnetic resonance imaging. Am J Physiol Renal Physiol 2013;305:F1428-F1435 
  12. Liang L, Chen WB, Chan KW, Li YG, Zhang B, Liang CH, et al. Using intravoxel incoherent motion MR imaging to study the renal pathophysiological process of contrast-induced acute kidney injury in rats: comparison with conventional DWI and arterial spin labelling. Eur Radiol 2016;26:1597-1605 
  13. Cai XR, Yu J, Zhou QC, Du B, Feng YZ, Liu XL. Use of intravoxel incoherent motion MRI to assess renal fibrosis in a rat model of unilateral ureteral obstruction. J Magn Reson Imaging 2016;44:698-706 
  14. Ichikawa S, Motosugi U, Ichikawa T, Sano K, Morisaka H, Araki T. Intravoxel incoherent motion imaging of the kidney: alterations in diffusion and perfusion in patients with renal dysfunction. Magn Reson Imaging 2013;31:414-417 
  15. Ding Y, Zeng M, Rao S, Chen C, Fu C, Zhou J. Comparison of biexponential and monoexponential model of diffusion-weighted imaging for distinguishing between common renal cell carcinoma and fat poor angiomyolipoma. Korean J Radiol 2016;17:853-863 
  16. Wang Y, Ren K, Liu Y, Sun WG, Wang JH, Zhang X, et al. Application of BOLD MRI and DTI for the evaluation of renal effect related to viscosity of iodinated contrast agent in a rat model. J Magn Reson Imaging 2017;46:1320-1331 
  17. Heyman SN, Rosen S, Rosenberger C. Renal parenchymal hypoxia, hypoxia adaptation, and the pathogenesis of radiocontrast nephropathy. Clin J Am Soc Nephrol 2008;3:288-296 
  18. Rosenberger C, Heyman SN, Rosen S, Shina A, Goldfarb M, Griethe W, et al. Up-regulation of HIF in experimental acute renal failure: evidence for a protective transcriptional response to hypoxia. Kidney Int 2005;67:531-542 
  19. Shukla R, Pandey N, Banerjee S, Tripathi YB. Effect of extract of Pueraria tuberosa on expression of hypoxia inducible factor-1α and vascular endothelial growth factor in kidney of diabetic rats. Biomed Pharmacother 2017;93:276-285 
  20. Manotham K, Tanaka T, Ohse T, Kojima I, Miyata T, Inagi R, et al. A biologic role of HIF-1 in the renal medulla. Kidney Int 2005;67:1428-1439 
  21. Rosenberger C, Griethe W, Gruber G, Wiesener M, Frei U, Bachmann S, et al. Cellular responses to hypoxia after renal segmental infarction. Kidney Int 2003;64:874-886 
  22. Zhao Q, Li J, Yan J, Liu S, Guo Y, Chen D, et al. Lycium barbarum polysaccharides ameliorates renal injury and inflammatory reaction in alloxan-induced diabetic nephropathy rabbits. Life Sci 2016;157:82-90 
  23. Papadimitriou A, Silva KC, Peixoto EB, Borges CM, Lopes de Faria JM, Lopes de Faria JB. Theobromine increases NAD+ /Sirt1 activity and protects the kidney under diabetic conditions. Am J Physiol Renal Physiol 2015;308:F209-F225 
  24. Pettersson G, Towart R, Grant D, Thyberg K, Golman K. The rabbit renal toxicity test: a sensitive in vivo test for the nephrotoxicity of contrast agents. Acad Radiol 2002;9 Suppl 1:S62-S64 
  25. Lauver DA, Carey EG, Bergin IL, Lucchesi BR, Gurm HS. Sildenafil citrate for prophylaxis of nephropathy in an animal model of contrast-induced acute kidney injury. PLoS One 2014;9:e113598 
  26. Wang JH, Ren K, Sun WG, Zhao L, Zhong HS, Xu K. Effects of iodinated contrast agents on renal oxygenation level determined by blood oxygenation level dependent magnetic resonance imaging in rabbit models of type 1 and type 2 diabetic nephropathy. BMC Nephrol 2014;15:140 
  27. Vivier PH, Storey P, Chandarana H, Yamamoto A, Tantillo K, Khan U, et al. Renal blood oxygenation level-dependent imaging contribution of R2 to R2* values. Invest Radiol 2013;48:501-508 
  28. Le Bihan D, Breton E, Lallemand D, Aubin ML, Vignaud J, Laval-Jeantet M. Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging. Radiology 1988;168:497-505 
  29. Tsamouri MM, Rapti M, Kouka P, Nepka C, Tsarouhas K, Soumelidis A, et al. Histopathological evaluation and redox assessment in blood and kidney tissues in a rabbit contrast-induced nephrotoxicity model. Food Chem Toxicol 2017;108(Pt A):186-193 
  30. Ari E, Kedrah AE, Alahdab Y, Bulut G, Eren Z, Baytekin O, et al. Antioxidant and renoprotective effects of paricalcitol on experimental contrast-induced nephropathy model. Br J Radiol 2012;85:1038-1043 
  31. Wang Y, Ren K, Xie L, Sun W, Liu Y, Li S. Effect of repeated injection of iodixanol on renal function in healthy Wistar rats using functional MRI. Biomed Res Int 2018;2018:7272485 
  32. Ries M, Basseau F, Tyndal B, Jones R, Deminiere C, Catargi B, et al. Renal diffusion and BOLD MRI in experimental diabetic nephropathy. Blood oxygen level-dependent. J Magn Reson Imaging 2003;17:104-113 
  33. Cheung JS, Fan SJ, Gao DS, Chow AM, Man K, Wu EX. Diffusion tensor imaging of liver fibrosis in an experimental model. J Magn Reson Imaging 2010;32:1141-1148 
  34. Wang J, Zhang Y, Yang X, Wang X, Zhang J, Fang J, et al. Time course study on the effects of iodinated contrast medium on intrarenal water transport function using diffusion-weighted MRI. J Magn Reson Imaging 2012;35:1139-1144 
  35. Yan YY, Hartono S, Hennedige T, Koh TS, Chan CM, Zhou L, et al. Intravoxel incoherent motion and diffusion tensor imaging of early renal fibrosis induced in a murine model of streptozotocin induced diabetes. Magn Reson Imaging 2017;38:71-76 
  36. Nakagawa T, Sato W, Kosugi T, Johnson RJ. Uncoupling of VEGF with endothelial NO as a potential mechanism for abnormal angiogenesis in the diabetic nephropathy. J Diabetes Res 2013;2013:184539 
  37. Rauch D, Drescher P, Pereira FJ, Knes JM, Will JA, Madsen PO. Comparison of iodinated contrast media-induced renal vasoconstriction in human, rabbit, dog, and pig arteries. Invest Radiol 1997;32:315-319 
  38. Heyman SN, Rosenberger C, Rosen S, Khamaisi M. Why is diabetes mellitus a risk factor for contrast-induced nephropathy? Biomed Res Int 2013;2013:123589 
  39. Melin J, Hellberg O, Akyurek LM, Kallskog O, Larsson E, Fellstrom BC. Ischemia causes rapidly progressive nephropathy in the diabetic rat. Kidney Int 1997;52:985-991 
  40. Goldfarb M, Rosenberger C, Abassi Z, Shina A, Zilbersat F, Eckardt KU, et al. Acute-on-chronic renal failure in the rat: functional compensation and hypoxia tolerance. Am J Nephrol 2006;26:22-33 
  41. Prasad P, Li LP, Halter S, Cabray J, Ye M, Batlle D. Evaluation of renal hypoxia in diabetic mice by BOLD MRI. Invest Radiol 2010;45:819-822 
  42. Basile DP, Donohoe DL, Roethe K, Mattson DL. Chronic renal hypoxia after acute ischemic injury: effects of L-arginine on hypoxia and secondary damage. Am J Physiol Renal Physiol 2003;284:F338-F348 
  43. Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int 2012;81:442-448 
  44. Fine LG, Orphanides C, Norman JT. Progressive renal disease: the chronic hypoxia hypothesis. Kidney Int Suppl 1998;65:S74-S78