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Vitamins for Prevention of Contrast-induced Acute Kidney Injury: A Systematic Review and Trial Sequential Analysis

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Abstract

Background

To date, universally accepted preventive measures for contrast-induced acute kidney injury (CI-AKI) do not exist, and they warrant further research.

Objective

The purpose of this study was to evaluate the efficacy of vitamins, including vitamin C and E, for prevention of CI-AKI.

Methods

We electronically searched the MEDLINE, EMBASE, and Cochrane databases. The outcome of interest was the incidence of CI-AKI.

Results

A total of 19 studies were included in this meta-analysis. Pooled analysis showed that vitamin C plus saline [relative risk (RR) = 0.63, 95% confidence interval (CI) 0.49–0.82, p = 0.0005] and vitamin E plus saline (RR = 0.39, 95% CI 0.24–0.62, p < 0.0001) significantly reduced the incidence of CI-AKI compared to saline alone. The effect of vitamin C plus saline was further confirmed by trial sequential analysis (TSA). However, TSA indicated that more trials are required to confirm the efficacy of vitamin E plus saline. There was no significant difference in preventing CI-AKI between vitamin C and N-acetylcysteine (NAC) (RR = 0.90, 95% CI 0.47–1.71, p = 0.75), between vitamin C plus NAC and saline (RR = 0.62, 95% CI 0.30–1.30, p =  0.20), as well as between vitamin C plus NAC and NAC (RR = 0.97, 95% CI 0.49–1.92, p = 0.93).

Conclusions

Vitamin C plus saline administration is effective at reducing the risk of CI-AKI. Evidence for the use of vitamin E plus saline in this context is encouraging, but more trials are required. Furthermore, this meta-analysis and TSA indicated insufficient power to draw a definitive conclusion on the effect of vitamin C plus NAC, versus saline or NAC alone, which needs to be explored further.

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References

  1. Bilasy ME, Oraby MA, Ismail HM, Maklady FA. Effectiveness of theophylline in preventing contrast-induced nephropathy after coronary angiographic procedures. J Interv Cardiol. 2012;25(4):404–10.

    Article  PubMed  Google Scholar 

  2. McCullough PA. Contrast-induced acute kidney injury. J Am Coll Cardiol. 2008;51(15):1419–28.

    Article  PubMed  Google Scholar 

  3. Azzalini L, Spagnoli V, Ly HQ. Contrast-induced nephropathy: from pathophysiology to preventive strategies. Can J Cardiol. 2016;32(2):247–55.

    Article  PubMed  Google Scholar 

  4. Seeliger E, Sendeski M, Rihal CS, Persson PB. Contrast-induced kidney injury: mechanisms, risk factors, and prevention. Eur Heart J. 2012;33(16):2007–15.

    Article  PubMed  Google Scholar 

  5. Jeong BY, Lee HY, Park CG, Kang J, Yu SL, Choi DR, et al. Oxidative stress caused by activation of NADPH oxidase 4 promotes contrast-induced acute kidney injury. PLoS One. 2018;13(1):e0191034.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Tasanarong A, Vohakiat A, Hutayanon P, Piyayotai D. New strategy of alpha- and gamma-tocopherol to prevent contrast-induced acute kidney injury in chronic kidney disease patients undergoing elective coronary procedures. Nephrol Dial Transplant. 2013;28(2):337–44.

    Article  PubMed  CAS  Google Scholar 

  7. Khaledifar A, Momeni A, Ebrahimi A, Kheiri S, Mokhtari A. Comparison of N-acetylcysteine, ascorbic acid, and normal saline effect in prevention of contrast-induced nephropathy. ARYA Atheroscler. 2015;11(4):228–32.

    PubMed  PubMed Central  Google Scholar 

  8. Albabtain MA, Almasood A, Alshurafah H, Alamri H, Tamim H. Efficacy of ascorbic acid, N-acetylcysteine, or combination of both on top of saline hydration versus saline hydration alone on prevention of contrast-Induced nephropathy: a prospective randomized study. J Interv Cardiol. 2013;26(1):90–6.

    Article  PubMed  Google Scholar 

  9. Navarese EP, Gurbel PA, Andreotti F, Kolodziejczak MM, Palmer SC, Dias S, et al. Prevention of contrast-induced acute kidney injury in patients undergoing cardiovascular procedures—a systematic review and network meta-analysis. PLoS ONE. 2017;12(2):e0168726.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Ali-Hasan-Al-Saegh S, Mirhosseini SJ, Ghodratipour Z, Sarrafan-Chaharsoughi Z, Rahimizadeh E, Karimi-Bondarabadi AA, et al. Strategies preventing contrast-induced nephropathy after coronary angiography: a comprehensive meta-analysis and systematic review of 125 randomized controlled trials. Angiology. 2017;68(5):389–413.

    Article  PubMed  CAS  Google Scholar 

  11. Giacoppo D, Gargiulo G, Buccheri S, Aruta P, Byrne RA, Cassese S, et al. Preventive strategies for contrast-induced acute kidney injury in patients undergoing percutaneous coronary procedures: evidence from a hierarchical Bayesian network meta-analysis of 124 trials and 28 240 patients. Circ Cardiovasc Interv. 2017;10(5):e004383.

    Article  PubMed  Google Scholar 

  12. Subramaniam RM, Suarez-Cuervo C, Wilson RF, Turban S, Zhang A, Sherrod C, et al. Effectiveness of prevention strategies for contrast-induced nephropathy: a systematic review and meta-analysis. Ann Intern Med. 2016;164(6):406–16.

    Article  PubMed  Google Scholar 

  13. Brueck M, Cengiz H, Hoeltgen R, Wieczorek M, Boedeker RH, Scheibelhut C, et al. Usefulness of N-acetylcysteine or ascorbic acid versus placebo to prevent contrast-induced acute kidney injury in patients undergoing elective cardiac catheterization: a single-center, prospective, randomized, double-blind, placebo-controlled trial. J Invasive Cardiol. 2013;25(6):276–83.

    PubMed  Google Scholar 

  14. Spargias K, Alexopoulos E, Kyrzopoulos S, Iokovis P, Greenwood DC, Manginas A, et al. Ascorbic acid prevents contrast-mediated nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention. Circulation. 2004;110(18):2837–42.

    Article  PubMed  CAS  Google Scholar 

  15. Sadat U, Usman A, Gillard JH, Boyle JR. Does ascorbic acid protect against contrast-induced acute kidney injury in patients undergoing coronary angiography: a systematic review with meta-analysis of randomized, controlled trials. J Am Coll Cardiol. 2013;62(23):2167–75.

    Article  PubMed  CAS  Google Scholar 

  16. Ali-Hasan-Al-Saegh S, Mirhosseini SJ, Ghodratipour Z, Sarafan-Chaharsoughi Z, Dehghan AM, Rahimizadeh E, et al. Protective effects of anti-oxidant supplementations on contrast-induced nephropathy after coronary angiography: an updated and comprehensive meta-analysis and systematic review. Kardiol Pol. 2016;74(7):610–26.

    Article  PubMed  Google Scholar 

  17. Su X, Xie X, Liu L, Lv J, Song F, Perkovic V, et al. Comparative effectiveness of 12 treatment strategies for preventing contrast-induced acute kidney injury: a systematic review and Bayesian network meta-analysis. Am J Kidney Dis. 2017;69(1):69–77.

    Article  PubMed  CAS  Google Scholar 

  18. Brok J, Thorlund K, Wetterslev J, Gluud C. Apparently conclusive meta-analyses may be inconclusive–trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta-analyses. Int J Epidemiol. 2009;38(1):287–98.

    Article  PubMed  Google Scholar 

  19. Wetterslev J, Jakobsen JC, Gluud C. Trial sequential analysis in systematic reviews with meta-analysis. BMC Med Res Methodol. 2017;17(1):39.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9 (W64).

    Article  PubMed  Google Scholar 

  21. Alonso A, Lau J, Jaber BL, Weintraub A, Sarnak MJ. Prevention of radiocontrast nephropathy with N-acetylcysteine in patients with chronic kidney disease: a meta-analysis of randomized, controlled trials. Am J Kidney Dis. 2004;43(1):1–9.

    Article  PubMed  CAS  Google Scholar 

  22. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;18(343):d5928.

    Article  Google Scholar 

  23. Friedrich JO, Adhikari NK, Beyene J. Inclusion of zero total event trials in meta-analyses maintains analytic consistency and incorporates all available data. BMC Med Res Methodol. 2007;7:5.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Dupuis C, Sonneville R, Adrie C, Gros A, Darmon M, Bouadma L, et al. Impact of transfusion on patients with sepsis admitted in intensive care unit: a systematic review and meta-analysis. Ann Intensive Care. 2017;7(1):5.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Thompson SG, Pocock SJ. Can meta-analyses be trusted? Lancet. 1991;338(8775):1127–30.

    Article  PubMed  CAS  Google Scholar 

  26. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. AlBalawi Z, McAlister FA, Thorlund K, Wong M, Wetterslev J. Random error in cardiovascular meta-analyses: how common are false positive and false negative results? Int J Cardiol. 2013;168(2):1102–7.

    Article  PubMed  Google Scholar 

  28. Roshanov PS, Dennis BB, Pasic N, Garg AX, Walsh M. When is a meta-analysis conclusive? A guide to trial sequential analysis with an example of remote ischemic preconditioning for renoprotection in patients undergoing cardiac surgery. Nephrol Dial Transplant. 2017;32(suppl 2):ii23–30.

    Article  PubMed  Google Scholar 

  29. Boscheri A, Weinbrenner C, Botzek B, Reynen K, Kuhlisch E, Strasser RH. Failure of ascorbic acid to prevent contrast-media induced nephropathy in patients with renal dysfunction. Clin Nephrol. 2007;68(5):279–86.

    Article  PubMed  CAS  Google Scholar 

  30. Dvorsak B, Kanic V, Ekart R, Bevc S, Hojs R. Ascorbic acid for the prevention of contrast-induced nephropathy after coronary angiography in patients with chronic renal impairment: a randomized controlled trial. Ther Apher Dial. 2013;17(4):384–90.

    Article  PubMed  CAS  Google Scholar 

  31. El-Fishawy HSN, Soliman A. Ascorbic acid and acetylcysteine for prevention of acute deterioration of renal function following elective aorto-iliac and coronary angioplasty. NDT Plus. 2010;3:300.

    Google Scholar 

  32. Grygier MJM, Araszkiewicz A, Kowal J, Mularek-Kubzdela T, Olasinska-Wisniewska A, Seniuk W, Popiel M, Lesiak M, Grajek S. Combined treatment with ascorbic acid and N-acetylcysteine prevents contrast-induced nephropathy in high-risk patients with acute myocardial infarction undergoing percutaneous coronary intervention. Eur Heart J. 2011;32:954–5.

    Google Scholar 

  33. Habib M, Hillis A, Hammad A. N-acetylcysteine and/or ascorbic acid versus placebo to prevent contrast-induced nephropathy in patients undergoing elective cardiac catheterization: the NAPCIN trial; A single-center, prospective, randomized trial. Saudi J Kidney Dis Transpl. 2016;27(1):55–61.

    Article  PubMed  Google Scholar 

  34. Hamdi SSW, Hraiech A, Jomaa W, Hamda KB, Maatouk F. Prevention of contrast induced nephropathy in patients undergoing coronarography with ascorbic acid. JACC. 2013;1:S22.

    Google Scholar 

  35. Jo SH, Koo BK, Park JS, Kang HJ, Kim YJ, Kim HL, et al. N-acetylcysteine versus AScorbic acid for preventing contrast-Induced nephropathy in patients with renal insufficiency undergoing coronary angiography NASPI study—a prospective randomized controlled trial. Am Heart J. 2009;157(3):576–83.

    Article  PubMed  CAS  Google Scholar 

  36. Komiyama KTT, Tanabe Y, Harumizu S. Impact of bolus administration of ascorbic acid to prevent contrast induced nephropathy undergoing emergent cardiovascular procedure. Am J Cardiol. 2011;1:29A.

    Article  Google Scholar 

  37. Nough H, Daryachahei R, Hadiani L, Najarzadegan MR, Mirzaee M, Hemayati R, et al. Ascorbic acid effect on CIN incidence in diabetic patient after coronary angiography. Adv Biomed Res. 2016;5:69.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Rezaei Y, Khademvatani K, Rahimi B, Khoshfetrat M, Arjmand N, Seyyed-Mohammadzad MH. Short-term high-dose vitamin E to prevent contrast medium-induced acute kidney injury in patients with chronic kidney disease undergoing elective coronary angiography: a randomized placebo-controlled trial. J Am Heart Assoc. 2016;5(3):e002919.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Tasanarong A, Piyayotai D, Thitiarchakul S. Protection of radiocontrast induced nephropathy by vitamin E (alpha tocopherol): a randomized controlled pilot study. J Med Assoc Thai. 2009;92(10):1273–81.

    PubMed  Google Scholar 

  40. Wenhua LDL, Yanbin Z, Tongda X, Hong Z, Fei H. Prevention of contrast-induced acute kidney injury with the sodium bicarbonate in ACS patients undergoing PCI. Heart. 2011;97:A110.

    Article  Google Scholar 

  41. Zhou L, Chen H. Prevention of contrast-induced nephropathy with ascorbic acid. Intern Med. 2012;51(6):531–5.

    Article  PubMed  CAS  Google Scholar 

  42. Briguori C, Airoldi F, D’Andrea D, Bonizzoni E, Morici N, Focaccio A, et al. Renal insufficiency following contrast media administration trial (REMEDIAL): a randomized comparison of 3 preventive strategies. Circulation. 2007;115(10):1211–7.

    Article  PubMed  CAS  Google Scholar 

  43. Kitzler TM, Jaberi A, Sendlhofer G, Rehak P, Binder C, Petnehazy E, et al. Efficacy of vitamin E and N-acetylcysteine in the prevention of contrast induced kidney injury in patients with chronic kidney disease: a double blind, randomized controlled trial. Wien Klin Wochenschr. 2012;124(9–10):312–9.

    Article  PubMed  CAS  Google Scholar 

  44. Addad F, Triki M, Ibn El Hadj Z, Laaroussi L, Marrakchi S, Ben Amara W, et al. Does oral ascorbic acid plus sodium bicarbonate protect against contrast-induced nephropathy in diabetic and/or renal insufficiency patients undergoing coronary angiography? A multicentre randomised controlled trial. EuroIntervention, EuroPCR Abstracts and Posters 2014.

  45. Shakeryan F, Sanati H, Fathi H, Firouzi A, Zahedmehr A, Valizadeh G, et al. Evaluation of combination therapy with vitamin C and pentoxifylline on preventing kidney failure secondary to intravenous contrast material in coronary angioplasty. Iran Heart J. 2013;14(3):17–21.

    Google Scholar 

  46. Smith OM, Wald R, Adhikari NK, Pope K, Weir MA, Bagshaw SM, et al. Standard versus accelerated initiation of renal replacement therapy in acute kidney injury (STARRT-AKI): study protocol for a randomized controlled trial. Trials. 2013;05(14):320.

    Article  Google Scholar 

  47. Feng Y, Huang X, Li L, Chen Z. N-acetylcysteine versus ascorbic acid or N-acetylcysteine plus ascorbic acid in preventing contrast-induced nephropathy: a meta-analysis. Nephrology (Carlton). 2017. https://doi.org/10.1111/nep.13068.

    Article  Google Scholar 

  48. Brok J, Thorlund K, Gluud C, Wetterslev J. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses. J Clin Epidemiol. 2008;61(8):763–9.

    Article  PubMed  Google Scholar 

  49. Thorlund K, Devereaux PJ, Wetterslev J, Guyatt G, Ioannidis JP, Thabane L, et al. Can trial sequential monitoring boundaries reduce spurious inferences from meta-analyses? Int J Epidemiol. 2009;38(1):276–86.

    Article  PubMed  Google Scholar 

  50. Fukumura H, Sato M, Kezuka K, Sato I, Feng X, Okumura S, et al. Effect of ascorbic acid on reactive oxygen species production in chemotherapy and hyperthermia in prostate cancer cells. J Physiol Sci. 2012;62(3):251–7.

    Article  PubMed  CAS  Google Scholar 

  51. Wang X, Quinn PJ. Vitamin E and its function in membranes. Prog Lipid Res. 1999;38(4):309–36.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The English in this document has been checked by at least two professional editors, both native speakers of English, from Textcheck Scientific and Technical Editing Service.

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Authors and Affiliations

Authors

Contributions

Research idea and study design: YX, JG, XZ; data acquisition: ZG, JG; data analysis/interpretation: ZG, JG, YX; statistical analysis: YX; the writing of the paper: ZG, XZ, BL; supervision or mentorship: JG, YX.

Corresponding authors

Correspondence to Jianjun Gao or Zhaoyan Gu.

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Funding

This study was supported in part by Hainan Natural Science Foundation of China to Z.Y.G (No.20168350) and Sanya Medical and Health Science and Technology Innovation Project of China to Z.Y.G (No. 2015YW24).

Conflict of Interest

Yongxing Xu, Xinming Zheng, Boran Liang, Jianjun Gao and Zhaoyan Gu declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

Ethical Standards

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. This article does not contain any studies with animals performed by any of the authors. Informed consent was not involved.

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Xu, Y., Zheng, X., Liang, B. et al. Vitamins for Prevention of Contrast-induced Acute Kidney Injury: A Systematic Review and Trial Sequential Analysis. Am J Cardiovasc Drugs 18, 373–386 (2018). https://doi.org/10.1007/s40256-018-0274-3

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