Skip to main content
SpringerLink
Log in

High mobility group box 1 and homocysteine as preprocedural predictors for contrast-induced acute kidney injury after percutaneous coronary artery intervention

  • Nephrology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Purpose

High mobility group box 1 (HMGB1) and homocysteine (Hcy) play important roles in contrast-induced acute kidney injury (CI-AKI). We compared HMGB1 to Hcy as preprocedural predictors for CI-AKI in coronary artery disease (CAD) patients after percutaneous coronary artery intervention (PCI).

Methods

We included 257 eligible patients who were categorized into CI-AKI ( +) and CI-AKI ( −) group. The differences in clinical characteristics and biochemical indexes between two groups were analyzed.

Results

We observed that thirty-eight (14.8%) of 257 eligible CAD patients developed CI-AKI. HMGB1 (14.65 [11.13–24.89] vs 10.88 [7.94–13.23], p < 0.001) and Hcy (14.07 [12.07–17.31] vs 12.09 [10.71–13.47], p < 0.001) increased significantly in CI-AKI ( +) group. Both age (r = 0.210, p = 0.001), serum creatinine (r = 0.509, p < 0.001), eGFR (r =  − 0.459, p < 0.001) and Hcy (r = 0.531, p < 0.001) were significantly correlated with HMGB1. Among all patients, HMGB1 (OR 1.181, 95% CI 1.081–1.290, p < 0.001) and Hcy (OR 1.260, 95% CI 1.066–1.489, p = 0.007) were independent predictors for the development of CI-AKI. We built the propensity score matching (PSM) using 38 pairs of patients. After adjustment, HMGB1 (OR 1.169, 95% CI 1.035–1.322, p = 0.012) and Hcy (OR 1.457, 95% CI 1.064–1.997, p = 0.019) were also independent predictors for the development of CI-AKI. Both HMGB1 (AUC: 0.704, 95% CI: 0.588–0.819, p = 0.002) and Hcy (AUC: 0.708, 95% CI: 0.593–0.823, p = 0.002) had predictive values for CI-AKI.

Conclusion

There is a significant positive association between HMGB1 and Hcy in CAD patients. Both HMGB1 and Hcy are potential preprocedural predictors of CI-AKI after PCI.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Availability of data and material

Not applicable.

References

  1. James MT, Ghali WA, Tonelli M, Faris P, Knudtson ML, Pannu N et al (2010) Acute kidney injury following coronary angiography is associated with a long-term decline in kidney function. Kidney Int 78(8):803–809. https://doi.org/10.1038/ki.2010.258

    Article  PubMed  Google Scholar 

  2. Amin AP, Bach RG, Caruso ML, Kennedy KF, Spertus JA (2017) Association of variation in contrast volume with acute kidney injury in patients undergoing percutaneous coronary intervention. JAMA Cardiol 2(9):1007–1012. https://doi.org/10.1001/jamacardio.2017.2156

    Article  PubMed  PubMed Central  Google Scholar 

  3. Tsai TT, Patel UD, Chang TI, Kennedy KF, Masoudi FA, Matheny ME et al (2014) Contemporary incidence, predictors, and outcomes of acute kidney injury in patients undergoing percutaneous coronary interventions: insights from the NCDR Cath-PCI registry. JACC Cardiovasc Interv 7(1):1–9. https://doi.org/10.1016/j.jcin.2013.06.016

    Article  PubMed  PubMed Central  Google Scholar 

  4. Weisbord SD, Palevsky PM, Kaufman JS, Wu H, Androsenko M, Ferguson RE et al (2020) Contrast-associated acute kidney injury and serious adverse outcomes following angiography. J Am Coll Cardiol 75(11):1311–1320. https://doi.org/10.1016/j.jacc.2020.01.023

    Article  PubMed  Google Scholar 

  5. Zdziechowska M, Gluba-Brzózka A, Franczyk B, Rysz J (2021) Biochemical markers in the prediction of contrast-induced acute kidney injury. Curr Med Chem 28(6):1234–1250. https://doi.org/10.2174/0929867327666200502015749

    Article  CAS  PubMed  Google Scholar 

  6. Stros M, Launholt D, Grasser KD (2007) The HMG-box: a versatile protein domain occurring in a wide variety of DNA-binding proteins. Cell Mol Life Sci 64(19–20):2590–2606. https://doi.org/10.1007/s00018-007-7162-3

    Article  CAS  PubMed  Google Scholar 

  7. Andersson U, Antoine DJ, Tracey KJ (2014) The functions of HMGB1 depend on molecular localization and post-translational modifications. J Intern Med 276(5):420–424. https://doi.org/10.1111/joim.12309

    Article  CAS  PubMed  Google Scholar 

  8. Singh GB, Zhang Y, Boini KM, Koka S (2019) High mobility group box 1 mediates TMAO-induced endothelial dysfunction. Int J Mol Sci 20(14):3570. https://doi.org/10.3390/ijms20143570

    Article  CAS  PubMed Central  Google Scholar 

  9. Cai J, Wen J, Bauer E, Zhong H, Yuan H, Chen AF (2015) The role HMGB1 in cardiovascular biology: danger signals. Antioxid Redox Signal 23(17):1351–1369. https://doi.org/10.1089/ars.2015.6408

    Article  CAS  PubMed  Google Scholar 

  10. Zhao Z, Hu Z, Zeng R, Yan Y (2020) HMGB1 in kidney diseases. Life Sci 259:188–203. https://doi.org/10.1016/j.lfs.2020.118203

    Article  CAS  Google Scholar 

  11. Chen Q, Guan X, Zuo X, Wang J, Yin W (2016) The role of high mobility group box 1 (HMGB1) in the pathogenesis of kidney diseases. Acta Pharm Sin B 6(3):183–188. https://doi.org/10.1016/j.apsb.2016.02.004

    Article  PubMed  PubMed Central  Google Scholar 

  12. Li S, Tang X, Peng L, Luo Y, Zhao Y, Chen L et al (2015) A head-to-head comparison of homocysteine and cystatin C as pre-procedurepredictors for contrast-induced nephropathy in patients undergoing coronary computed tomography angiography. Clin Chim Acta 444:86–91. https://doi.org/10.1016/j.cca.2015.02.019

    Article  CAS  PubMed  Google Scholar 

  13. Barbieri L, Verdoia M, Schaffer A, Niccoli G, Perrone-Filardi P, Bellomo G et al (2014) Elevated homocysteine and the risk of contrast-induced nephropathy: a cohort study. Angiology 66(4):333–338. https://doi.org/10.1177/0003319714533401

    Article  CAS  PubMed  Google Scholar 

  14. Kim SJ, Choi D, Ko YG, Kim JS, Han SH, Kim BK et al (2011) Relation of homocysteinemia to contrast-induced nephropathy in patients undergoing percutaneous coronary intervention. Am J Cardiol 108(8):1086–1091. https://doi.org/10.1016/j.amjcard.2011.06.010

    Article  CAS  PubMed  Google Scholar 

  15. Ma Y, Zhang Z, Chen R, Shi R, Zeng P, Chen R et al (2019) NRP1 regulates HMGB1 in vascular endothelial cells under high homocysteine condition. Am J Physiol Heart Circ Physiol 316(5):H1039-1046. https://doi.org/10.1152/ajpheart.00746.2018

    Article  CAS  PubMed  Google Scholar 

  16. Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T et al (2012) Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 367(1):20–29. https://doi.org/10.1056/NEJMoa1114248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fliser D, Laville M, Covic A, Fouque D, Vanholder R, Juillard L et al (2012) A European Renal Best Practice (ERBP) position statement on the Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines on acute kidney injury: part 1: definitions, conservative management and contrast-induced nephropathy. Nephrol Dial Transplant 27(12):4263–4272. https://doi.org/10.1093/ndt/gfs375

    Article  PubMed  PubMed Central  Google Scholar 

  18. Seeliger E, Sendeski M, Rihal CS, Persson PB (2012) Contrast-induced kidney injury: mechanisms, risk factors, and prevention. Eur Heart J 33(16):2007–2015. https://doi.org/10.1093/eurheartj/ehr494

    Article  PubMed  Google Scholar 

  19. Sendeski MM (2011) Pathophysiology of renal tissue damage by iodinated contrast media. Clin Exp Pharmacol Physiol 38(5):292–299. https://doi.org/10.1111/j.1440-1681.2011.05503.x

    Article  CAS  PubMed  Google Scholar 

  20. Hizoh I, Haller C (2002) Radiocontrast-induced renal tubular cell apoptosis: hypertonic versus oxidative stress. Invest Radiol 37(8):428–434. https://doi.org/10.1097/00004424-200208000-00003

    Article  PubMed  Google Scholar 

  21. Heyman SN, Rosen S, Rosenberger C (2008) Renal parenchymal hypoxia, hypoxia adaptation, and the pathogenesis of radiocontrast nephropathy. Clin J Am Soc Nephrol 3(1):288–296. https://doi.org/10.2215/CJN.02600607

    Article  PubMed  Google Scholar 

  22. Bruchfeld A, Qureshi AR, Lindholm B, Barany P, Yang L, Stenvinkel P, Tracey KJ (2008) High mobility group box protein-1 correlates with renal function in chronic kidney disease (CKD). Mol Med 14(3–4):109–115. https://doi.org/10.2119/2007-00107.Bruchfeld

    Article  CAS  PubMed  Google Scholar 

  23. Pellegrini L, Foglio E, Pontemezzo E, Germani A, Russo MA, Limana F (2019) HMGB1 and repair: focus on the heart. Pharmacol Ther 196:160–182. https://doi.org/10.1016/j.pharmthera.2018.12.005

    Article  CAS  PubMed  Google Scholar 

  24. Wu H, Ma J, Wang P, Corpuz TM, Panchapakesan U, Wyburn KR, Chadban SJ (2010) HMGB1 contributes to kidney ischemia reperfusion injury. J Am Soc Nephrol 21(11):1878–1890. https://doi.org/10.1681/ASN.2009101048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhang C, Dong H, Chen F, Wang Y, Ma J, Wang G (2019) The HMGB1-RAGE/TLR-TNF-α signaling pathway may contribute to kidney injury induced by hypoxia. Exp Ther Med 17(1):17–26. https://doi.org/10.3892/etm.2018.6932

    Article  CAS  PubMed  Google Scholar 

  26. Chen CB, Liu LS, Zhou J, Wang XP, Han M, Jiao XY, He XS, Yuan XP (2017) Up-regulation of HMGB1 exacerbates renal ischemia-reperfusion injury by stimulating inflammatory and immune responses through the TLR4 signaling pathway in mice. Cell Physiol Biochem 41(6):2447–2460. https://doi.org/10.1159/000475914

    Article  CAS  PubMed  Google Scholar 

  27. Yao D, Wang S, Wang M, Lu W (2018) Renoprotection of dapagliflozin in human renal proximal tubular cells via the inhibition of the high mobility group box 1-receptor for advanced glycation end products-nuclear factor-κB signaling pathway. Mol Med Rep 18(4):3625–3630. https://doi.org/10.3892/mmr.2018.9393

    Article  CAS  PubMed  Google Scholar 

  28. Lau A, Wang S, Liu W, Haig A, Zhang ZX, Jevnikar AM (2014) Glycyrrhizic acid ameliorates HMGB1-mediated cell death and inflammation after renal ischemia reperfusion injury. Am J Nephrol 40(1):84–95. https://doi.org/10.1159/000364908

    Article  CAS  PubMed  Google Scholar 

  29. Miura K, Sahara H, Sekijima M, Kawai A, Waki S, Nishimura H et al (2014) Protective effect of neutralization of the extracellular high-mobility group box 1 on renal ischemia-reperfusion injury in miniature swine. Transplantation 98(9):937–943. https://doi.org/10.1097/TP.0000000000000358

    Article  CAS  PubMed  Google Scholar 

  30. Jin SA, Kim SK, Seo HJ, Jeong JY, Ahn KT, Kim JH et al (2016) Beneficial effects of necrosis modulator, indole derivative necroX-7, on renalischemia-reperfusion injury in rats. Transplant Proc 48(1):199–204. https://doi.org/10.1016/j.transproceed.2015.12.018

    Article  CAS  PubMed  Google Scholar 

  31. Guan XF, Chen QJ, Zuo XC, Guo R, Peng XD, Wang JL et al (2017) Contrast media-induced renal inflammation is mediated through HMGB1 and its receptors in human tubular cells. DNA Cell Biol 36(1):67–76. https://doi.org/10.1089/dna.2016.3463

    Article  CAS  PubMed  Google Scholar 

  32. Oh H, Choi A, Seo N, Lim JS, You JS, Chung YE (2021) Protective effect of glycyrrhizin, a direct HMGB1 inhibitor, on post-contrast acute kidney injury. Sci Rep 11(1):15625. https://doi.org/10.1038/s41598-021-94928-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Morcos R, Kucharik M, Bansal P, Al Taii H, Manam R, Casale J et al (2019) Contrast-induced acute kidney injury: review and practical update. Clin Med Insights Cardiol 13:1523458280. https://doi.org/10.1177/1179546819878680

    Article  Google Scholar 

  34. Romano G, Briguori C, Quintavalle C, Zanca C, Rivera NV, Colombo A, Condorelli G (2008) Contrast agents and renal cell apoptosis. Eur Heart J 29(20):2569–2576. https://doi.org/10.1093/eurheartj/ehn197

    Article  CAS  PubMed  Google Scholar 

  35. Gao W, Cui H, Li Q, Zhong H, Yu J, Li P, He X (2020) Upregulation of microRNA-218 reduces cardiac microvascular endothelial cells injury induced by coronary artery disease through the inhibition of HMGB1. J Cell Physiol 235(3):3079–3095. https://doi.org/10.1002/jcp.29214

    Article  CAS  PubMed  Google Scholar 

  36. Leng Y, Chen R, Chen R, He S, Shi X, Zhou X et al (2020) HMGB1 mediates homocysteine-induced endothelial cells pyroptosis via cathepsin V-dependent pathway. Biochem Biophys Res Commun 532(4):640–646. https://doi.org/10.1016/j.bbrc.2020.08.091

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledges use of the services and facilities of the Clinical Medical Experiment Center of Guangxi Medical University.

Funding

This study was supported by The National Natural Science Foundation of China (81460063) and Innovative Research Team Project of Guangxi Natural Science Foundation (Grant No. 2018GXNSFGA281006).

Author information

Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, No 6, Shuangyong Road, Nanning, 530021, China

    Changhua Mo, Xiao Ma, Wen Jian, Qili Huang, Wenbo Zheng, Zhijie Yang, Yutao Xu & Chun Gui

  2. Guangxi Key Laboratory Base of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention, No 6, Shuangyong Road, Nanning, 530021, China

    Changhua Mo, Xiao Ma, Wen Jian, Qili Huang, Wenbo Zheng, Zhijie Yang, Yutao Xu & Chun Gui

  3. Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, No 6, Shuangyong Road, Nanning, 530021, China

    Changhua Mo, Xiao Ma, Wen Jian, Qili Huang, Wenbo Zheng, Zhijie Yang, Yutao Xu & Chun Gui

Authors
  1. Changhua Mo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wen Jian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qili Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wenbo Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhijie Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yutao Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chun Gui
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CM and GC made significant contributions to the design of this article. CM analyzed and interpreted the data and drafted this paper. CM and XM revised the paper. XM, WJ, QH, WZ, ZY, YX collected the original data and samples.

Corresponding author

Correspondence to Chun Gui.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The research was in compliance with the Declaration of Helsinki and was approved by the ethical committees of the First Affiliated Hospital of Guangxi Medical University.

Consent to participate

All participants have given informed consent before inclusion in the present study.

Consent for publication

All the co-authors agreed to the publication of this paper.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mo, C., Ma, X., Jian, W. et al. High mobility group box 1 and homocysteine as preprocedural predictors for contrast-induced acute kidney injury after percutaneous coronary artery intervention. Int Urol Nephrol 54, 1663–1671 (2022). https://doi.org/10.1007/s11255-021-03050-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-021-03050-y

Keywords

Search

Navigation