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Assessing renal changes after remote ischemic preconditioning (RIPC) of the upper extremity using BOLD imaging at 3T

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Abstract

Objective

Acute kidney injury (AKI) is an important risk factor for a number of adverse outcomes including end-stage renal disease and cardiovascular morbidity and mortality. Whilst many clinical situations that can induce AKI are known—e.g. drug toxicity, contrast agent exposure or ischemia during surgery—targeted preventive or therapeutic measures are still lacking. As to renoprotective strategies, remote ischemic preconditioning (RIPC) is one of the most promising novel approaches and has been examined by a number of clinical trials. The aim of this study was to use blood oxygenation level-dependent (BOLD) MRI as a surrogate parameter to assess the effect of RIPC in healthy volunteers.

Materials and methods

In this IRB-approved, prospective study, 40 healthy volunteers were stratified with 20 undergoing an RIPC procedure (i.e. RIPC group) with a transient ischemia of the right arm, and 20 undergoing a sham procedure. Before and after the procedure, both kidneys of all participants were scanned using a 12-echo mGRE sequence for functional BOLD imaging at 3T. For each volunteer, 180 ROIs were placed in the cortex and the medulla of the kidneys. Ultimately, R2* values, which have an inverse correlation with the oxygenation level of tissue, were averaged for the RIPC and control groups.

Results

Following intervention, mean R2* values significantly decreased in the RIPC group in both the cortex (18.6 ± 2.3 vs. 17.5 ± 1.7 Hz; p = 0.0047) and medulla (34 ± 5.2 vs. 32.2 ± 4.2 Hz; p = 0.0001). However, no significant differences were observed in the control group.

Conclusion

RIPC can be non-invasively assessed in healthy volunteers using BOLD MRI at 3T, demonstrating a higher oxygen content in kidney tissue. This study presents a first-in-man trial establishing a quantifiable readout of RIPC and its effects on kidney physiology. BOLD measurements may advance clinical trials in further evaluating RIPC for future clinical care.

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References

  1. McCullough PA, Adam A, Becker CR, Davidson C, Lameire N, Stacul F, Tumlin J, CIN Consensus Working Panel (2006) Epidemiology and prognostic implications of contrast-induced nephropathy. Am J Cardiol 98:5K–13K

    Article  PubMed  CAS  Google Scholar 

  2. Persson PB, Tepel M (2006) Contrast medium-induced nephropathy: the pathophysiology. Kidney Int Suppl 100:S8–10

    Article  CAS  Google Scholar 

  3. Liss P, Nygren A, Olsson U, Ulfendahl HR, Erikson U (1996) Effects of contrast media and mannitol on renal medullary blood flow and red cell aggregation in the rat kidney. Kidney Int 49:1268–1275

    Article  PubMed  CAS  Google Scholar 

  4. Subramaniam RM, Suarez-Cuervo C, Wilson RF, Turban S, Zhang A, Sherrod C, Aboagye J, Eng J, Choi MJ, Hutfless S, Bass EB (2016) Effectiveness of prevention strategies for contrast-induced nephropathy: a systematic review and meta-analysis. Ann Intern Med 164:406–416

    Article  PubMed  Google Scholar 

  5. Davenport MS, Cohan RH, Ellis JH (2015) Contrast media controversies in 2015: imaging patients with renal impairment or risk of contrast reaction. Am J Roentgenol 204:1174–1181

    Article  Google Scholar 

  6. Mitchell JR, Verweij M, Brand K, van de Ven M, Goemaere N, van den Engel S, Chu T, Forrer F, Müller C, de Jong M, van IJcken W, IJzermans JN, Hoeijmakers JH, de Bruin RW (2010) Short-term dietary restriction and fasting precondition against ischemia reperfusion injury in mice. Aging Cell 9:40–53

    Article  PubMed  CAS  Google Scholar 

  7. Cochrane J, Williams BT, Banerjee A, Harken AH, Burke TJ, Cairns CB, Shapiro JI (1999) Ischemic preconditioning attenuates functional, metabolic, and morphologic injury from ischemic acute renal failure in the rat. Ren Fail 21:135–145

    Article  PubMed  CAS  Google Scholar 

  8. Zuk A, Bonventre JV (2015) Acute kidney injury: can remote ischaemic preconditioning prevent AKI? Nat Rev Nephrol 11:512–513

    Article  PubMed  PubMed Central  Google Scholar 

  9. Er F, Nia AM, Dopp H, Hellmich M, Dahlem KM, Caglayan E, Kubacki T, Benzing T, Erdmann E, Burst V, Gassanov N (2012) Ischemic preconditioning for prevention of contrast medium-induced nephropathy: randomized pilot RenPro trial (renal protection trial). Circulation 126:296–303

    Article  PubMed  CAS  Google Scholar 

  10. Meybohm P, Bein B, Brosteanu O, Cremer J, Gruenewald M, Stoppe C, Coburn M, Schaelte G, Böning A, Niemann B, Roesner J, Kletzin F, Strouhal U, Reyher C, Laufenberg-Feldmann R, Ferner M, Brandes IF, Bauer M, Stehr SN, Kortgen A, Wittmann M, Baumgarten G, Meyer-Treschan T, Kienbaum P, Heringlake M, Schön J, Sander M, Treskatsch S, Smul T, Wolwender E, Schilling T, Fuernau G, Hasenclever D, Zacharowski K, RIPHeart Study Collaborators (2015) A multicenter trial of remote ischemic preconditioning for heart surgery. N Engl J Med 373:1397–1407

    Article  PubMed  CAS  Google Scholar 

  11. Zarbock A, Kellum JA, Van Aken H, Schmidt C, Küllmar M, Rosenberger P, Martens S, Görlich D, Meersch M (2017) Long-term effects of remote ischemic preconditioning on kidney function in high-risk cardiac surgery patients: follow-up results from the renal RIP trial. Anesthesiology 126:787–798

    Article  PubMed  Google Scholar 

  12. Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas JM, Pepper J, Robertson S, Xenou M, Clayton T, Yellon DM (2016) Effect of remote ischemic preconditioning on clinical outcomes in patients undergoing coronary artery bypass graft surgery (ERICCA study): a multicentre double-blind randomised controlled clinical trial. NIHR J Libr, Southampton (UK)

    Google Scholar 

  13. Zhou C, Jeon Y, Meybohm P, Young PJ, Li L, Hausenloy DJ (2016) Renoprotection by remote ischemic conditioning during elective coronary revascularization: a systematic review and meta-analysis of randomized controlled trials. Int J Cardiol 222:295–302

    Article  PubMed  Google Scholar 

  14. Zhou C, Bulluck H, Fang N, Li L, Hausenloy DJ (2017) Age and surgical complexity impact on renoprotection by remote ischemic preconditioning during adult cardiac surgery: a meta analysis. Sci Rep 7:215

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Pierce B, Bole I, Patel V, Brown DL (2017) Clinical outcomes of remote ischemic preconditioning prior to cardiac surgery: a meta-analysis of randomized controlled trials. J Am Heart Assoc. doi:10.1161/JAHA.116.004666

    Article  PubMed  PubMed Central  Google Scholar 

  16. Menting TP, Wever KE, Ozdemir-van Brunschot DM, Van der Vliet DJ, Rovers MM, Warle MC (2017) Ischaemic preconditioning for the reduction of renal ischaemia reperfusion injury. Cochrane Database Syst Rev 3:CD010777

    PubMed  Google Scholar 

  17. Kork F, Eltzschig HK (2017) The devil is in the detail: remote ischemic preconditioning for perioperative kidney protection. Anestehsiology 126:763–765

    Article  Google Scholar 

  18. Sukkar L, Hong D, Wong MG, Badve SV, Rogers K, Perkovic V, Walsh M, Yu X, Hillis GS, Gallagher M, Jardine M (2016) Effects of ischaemic conditioning on major clinical outcomes in people undergoing invasive procedures: systematic review and meta-analysis. BMJ 355:i5599

    Article  PubMed  PubMed Central  Google Scholar 

  19. Zhang Y, Zhang X, Chi D, Wang S, Wei H, Yu H, Li Q, Liu B (2016) Remote ischemic preconditioning for prevention of acute kidney injury in patients undergoing on-pump cardiac surgery: a systematic review and meta-analysis. Medicine (Baltimore) 95:e3465

    Article  Google Scholar 

  20. Bei WJ, Duan CY, Chen JY, Wang K, Liu YH, Kiu Y, Tan N (2016) Remote ischemic conditioning for preventing contrast-induced acute kidney injury in patients undergoing percutaneous coronary interventions/coronary angiography: a meta-analysis of randomized controlled trials. J Cardiovasc Pharmacol Ther 21:53–63

    Article  PubMed  CAS  Google Scholar 

  21. Michaely HJ, Metzger L, Haneder S, Hansmann J, Schoenberg SO, Attenberger UI (2012) Renal BOLD-MRI does not reflect renal function in chronic kidney disease. Kidney Int 81:684–689

    Article  PubMed  CAS  Google Scholar 

  22. Prasad PV, Edelman RR, Epstein FH (1996) Noninvasive evaluation of intrarenal oxygenation with BOLD MRI. Circulation 94:3271–3275

    Article  PubMed  CAS  Google Scholar 

  23. Li LP, Thacker J, Lu J, Franklin T, Zhou Y, Papadopulou MV, Solomon R, Prasad PV (2014) Efficacy of preventive interventions for iodinated contrast-induced acute kidney injury evaluated by intrarenal oxygenation as an early marker. Invest Radiol 49:647–652

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Vinten-Johansen J, Yellon DM, Opie LH (2005) Postconditioning: a simple, clinically applicable procedure to improve revascularization in acute myocardial infarction. Circulation 112:2085–2088

    Article  PubMed  Google Scholar 

  25. Kin H, Zhao ZQ, Sun HY, Wang NP, Corvera JS, Halkos ME, Kerendi F, Guyton RA, Vinten-Johansen J (2004) Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion. Cardiovasc Res 62:74–85

    Article  PubMed  CAS  Google Scholar 

  26. Lang SC, Elsasser A, Scheler C, Vetter S, Tiefenbacher CP, Kubler W, Katus HA, Vogt AM (2006) Myocardial preconditioning and remote renal preconditioning: identifying a protective factor using proteomic methods? Basic Res Cardiol 101:149–158

    Article  PubMed  CAS  Google Scholar 

  27. Olenchock BA, Moslehi J, Baik AH, Davidson SM, Williams J, Gibson WJ, Chakraborty AA, Pierce KA, Miller CM, Hanse EA, Kelekar A, Sullivan LB, Wagers AJ, Clish CB, Vander Heiden MG, Kaelin WG Jr (2016) EGLN1 inhibition and rerouting of α-ketoglutarate suffice for remote ischemic protection. Cell 164:884–895

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Brezis M, Rosen S (1995) Hypoxia of the renal medulla—it’s implications for disease. N Engl J Med 332:647–655

    Article  PubMed  CAS  Google Scholar 

  29. Persson PB, Hansell P, Liss P (2005) Pathophysiology of contrast medium-induced nephropathy. Kidney Int 68:14–22

    Article  PubMed  CAS  Google Scholar 

  30. Geenen RW, Kingma HJ, van der Molen AJ (2013) Contrast-induced nephropathy: pharmacology, pathophysiology and prevention. Insights Imaging 4:811–820

    Article  PubMed  PubMed Central  Google Scholar 

  31. Wang JH, Ren K, Sun WG, Zhao L, Zhong HS, Xu K (2014) 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 15:140

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Zhang Y, Wang J, Yang X, Wang X, Zhang J, Fang J, Jiang X (2012) The serial effect of iodinated contrast media on renal hemodynamics and oxygenation as evaluated by ASL and BOLD MRI. Contrast Media Mol Imaging 7:418–425

    Article  PubMed  CAS  Google Scholar 

  33. Pedersen M, Dissing TH, Morkenborg J, Stodkilde-Jorgensen H, Hansen LH, Pedersen LB, Grenier N, Frokiaer J (2005) Validation of quantitative BOLD MRI measurements in kidney: application to unilateral ureteral obstruction. Kidney Int 67:2305–2312

    Article  PubMed  Google Scholar 

  34. Tumkur SM, Vu AT, Li LP, Pierchala L, Prasad PV (2006) Evaluation of intra-renal oxygenation during water diuresis: a time-resolved study using BOLD MRI. Kidney Int 70:139–143

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Li LP, Vu AT, Li BS, Dunkle E, Prasad PV (2004) Evaluation of intrarenal oxygenation by BOLD MRI at 3.0T. J Magn Reson Imaging 20:901–904

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Institute of Diagnostic and Interventional Radiology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany

    Florian Siedek, Thorsten Persigehl, David Maintz & Stefan Haneder

  2. Department II of Internal Medicine and Center for Molecular Medicine Cologne, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany

    Roman-Ulrich Mueller, Volker Burst & Thomas Benzing

Authors
  1. Florian Siedek
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  2. Thorsten Persigehl
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  3. Roman-Ulrich Mueller
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  4. Volker Burst
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  5. Thomas Benzing
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  6. David Maintz
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  7. Stefan Haneder
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Contributions

Siedek: protocol/project development, data collection and management, and data analysis. Persigehl: protocol/project development and data analysis. Mueller: protocol/project development and data analysis. Burst: protocol/project development. Benzing: protocol/project development. Maintz: protocol/project development. Haneder: protocol/project development, data collection and management, and data analysis.

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Correspondence to Florian Siedek.

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The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Siedek, F., Persigehl, T., Mueller, RU. et al. Assessing renal changes after remote ischemic preconditioning (RIPC) of the upper extremity using BOLD imaging at 3T. Magn Reson Mater Phy 31, 367–374 (2018). https://doi.org/10.1007/s10334-017-0658-4

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  • DOI: https://doi.org/10.1007/s10334-017-0658-4

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