Skip to main content
SpringerLink
Log in

Compensatory elevated serum intermedin levels are associated with increased vascular calcification in hemodialysis patients

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

Abstract

Introduction

Vascular calcification (VC), which is a pathological process of abnormal calcium and phosphorus deposition in blood vessels, valves, heart and other tissues, is highly prevalent and predicts mortality in dialysis patients. Its mechanisms are complex and unclear. We presume that intermedin (IMD), a kind of small molecule active peptide, may play roles in VC in hemodialysis (HD) patients. This study aims to evaluate serum IMD levels and establish their relation to VC and other parameters in HD patients.

Methods

A total of 116 patients on maintenance HD treatment and 52 age- and sex-matched healthy controls were enrolled in this study. Serum IMD levels were measured by radioimmunoassay (RIA). VC was evaluated by abdominal aortic calcification scores.

Results

Serum IMD levels were significantly lower in HD patients than in controls [24.89 (13.55, 50.24) pg/ml vs. 137.79 (93.21, 201.64) pg/ml, P < 0.0001]. In addition, IMD was negatively correlated with the serum phosphate level (P = 0.036) in HD patients. However, compared with the group whose IMD levels were above the median, patients with IMD levels less than the median had a lower incidence of VC (P = 0.031). Multivariate logistic regression analyses revealed that serum IMD levels more than 24.89 pg/ml (P = 0.014, OR = 0.285), higher serum iPTH levels (P < 0.0001, OR = 1.093) and older age (P = 0.009, OR = 1.003) were significant independent determinant factors for VC in HD patients.

Conclusion

The serum IMD levels were significantly lower in HD patients than that in healthy group. In addition to higher PTH levels and older age, compensatory elevated IMD levels may be an independently determinant factor for VC in HD patients. This was the first study about IMD and VC in dialysis patients.

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

Similar content being viewed by others

Availability of data and materials

The data and materials in the study were available.

Code availability

The code in the study were available.

References

  1. Gungor O, Kocyigit I, Yilmaz MI, Sezer S (2018) Role of vascular calcification inhibitors in preventing vascular dysfunction and mortality in hemodialysis patients. Semin Dial 31(1):72–81. https://doi.org/10.1111/sdi.12616

    Article  PubMed  Google Scholar 

  2. He L, He WY, La-Ta A, Yang WL, Zhang AH (2018) Lower serum irisin levels are associated with increased vascular calcification in hemodialysis patients. Kidney Blood Press Res 43(1):287–295. https://doi.org/10.1159/000487689

    Article  CAS  PubMed  Google Scholar 

  3. Roh J, Chang CL, Bhalla A, Klein C, Hsu SY (2004) Intermedin is a calcitonin/calcitonin gene-related peptide family peptide acting through the calcitonin receptor-like receptor/receptor activity-modifying protein receptor complexes. J Biol Chem 279(8):7264–7274. https://doi.org/10.1074/jbc.M305332200

    Article  CAS  PubMed  Google Scholar 

  4. Ni X, Zhang J, Tang C, Qi Y (2014) Intermedin/adrenomedullin2: an autocrine/paracrine factor in vascular homeostasis and disease. Sci Chin Life Sci 57(8):781–789. https://doi.org/10.1007/s11427-014-4701-7

    Article  CAS  Google Scholar 

  5. Chang JR, Duan XH, Zhang BH, Teng X, Zhou YB, Liu Y, Yu YR, Zhu Y, Tang CS, Qi YF (2013) Intermedin1-53 attenuates vascular smooth muscle cell calcification by inhibiting endoplasmic reticulum stress via cyclic adenosine monophosphate/protein kinase A pathway. Exp Biol Med (Maywood) 238(10):1136–1146. https://doi.org/10.1177/1535370213502619

    Article  CAS  Google Scholar 

  6. Cai Y, Xu MJ, Teng X, Zhou YB, Chen L, Zhu Y, Wang X, Tang CS, Qi YF (2010) Intermedin inhibits vascular calcification by increasing the level of matrix gamma-carboxyglutamic acid protein. Cardiovasc Res 85(4):864–873. https://doi.org/10.1093/cvr/cvp366

    Article  CAS  PubMed  Google Scholar 

  7. Chen Y, Zhang LS, Ren JL, Zhang YR, Wu N, Jia MZ, Yu YR, Ning ZP, Tang CS, Qi YF (2020) Intermedin1-53 attenuates aging-associated vascular calcification in rats by upregulating sirtuin 1. Aging (Albany NY) 12(7):5651–5674. https://doi.org/10.18632/aging.102934

    Article  CAS  Google Scholar 

  8. Kauppila LI, Polak JF, Cupples LA, Hannan MT, Kiel DP, Wilson PW (1997) New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study. Atherosclerosis 132(2):245–250. https://doi.org/10.1016/S0021-9150(97)00106-8

    Article  CAS  PubMed  Google Scholar 

  9. Lee SJ, Lee IK, Jeon JH (2020) Vascular calcification-new insights into its mechanism. Int J Mol Sci 21(8):2685. https://doi.org/10.3390/ijms21082685

    Article  CAS  PubMed Central  Google Scholar 

  10. Wang Y, Mi Y, Tian J, Qiao X, Su X, Kang J, Wu ZJ, Wang GQ, Zhou XS, Zhou Y, Li RS (2020) Intermedin alleviates renal ischemia-reperfusion injury and enhances neovascularization in wistar rats. Drug Des Dev Ther 14:4825–4834. https://doi.org/10.2147/DDDT.S253019

    Article  CAS  Google Scholar 

  11. Morimoto R, Satoh F, Murakami O, Totsune K, Suzuki T, Sasano H, Ito S, Takahashi K (2007) Expression of adrenomedullin2/intermedin in human brain, heart, and kidney. Peptides 28(5):1095–1103. https://doi.org/10.1016/j.peptides.2007.01.018

    Article  CAS  PubMed  Google Scholar 

  12. Dong H, Zhou Y, Wang Y, Zhou Q, Zhang Y, Gan X, Luo YK, Li RS (2019) The protective role of intermedin in promoting angiogenesis during renal fibrosis. Gene 688:34–43. https://doi.org/10.1016/j.gene.2018.11.057

    Article  CAS  PubMed  Google Scholar 

  13. Qiao X, Wang L, Wang Y, Su X, Qi Y, Fan Y, Peng ZQ (2017) Intermedin inhibits unilateral ureteral obstruction-induced oxidative stress via NADPH oxidase Nox4 and cAMP-dependent mechanisms. Ren Fail 39(1):652–659. https://doi.org/10.1080/0886022X.2017.1361839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lei JF, Zhou Y, Dong HL, Zhao XY, Luo YK, Li RS (2017) Study on glomerular microvascular injury and repair in patients with IgA nephropathy and its relationship with intermedin. Chin J Nephrol 33(6):416–421

    Google Scholar 

  15. Chen P, Zhou Y, Zhou C, Wang QH, Li RS, Wen T, Mao M (2013) Study of changes of plasma intermedin level in patients with chronic kidney disease and its relationship with the levels of homocysteine and cystatin-C. Chin J Clin 7(21):9448–9452

    Google Scholar 

  16. Carrillo-López N, Panizo S, Alonso-Montes C, Martínez-Arias L, Avello N, Sosa P, Dusso AS, Cannata-Andía JB, Naves-Díaz M (2019) High-serum phosphate and parathyroid hormone distinctly regulate bone loss and vascular calcification in experimental chronic kidney disease. Nephrol Dial Transplant 34(6):934–941. https://doi.org/10.1093/ndt/gfy287

    Article  CAS  PubMed  Google Scholar 

  17. Chang JR, Guo J, Wang Y, Hou YL, Lu WW, Zhang JS, Yu YR, Xu MJ, Liu XY, Wang XJ, Guan YF, Zhu Y, Du J, Tang CS, Qi YF (2016) Intermedin1–53 attenuates vascular calcification in rats with chronic kidney disease by upregulation of α-Klotho. Kidney Int 89(3):586–600. https://doi.org/10.1016/j.kint.2015.12.029

    Article  CAS  PubMed  Google Scholar 

  18. Disthabanchong S (2012) Vascular calcification in chronic kidney disease: pathogenesis and clinical implication. World J Nephrol 1(2):43–53. https://doi.org/10.5527/wjn.v1.i2.43

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We are grateful to all staff of the Hemodialysis Dialysis Center at Peking University Third Hospital and patients who participated in this project.

Funding

This article was supported by the National Natural Science Foundation of China under Grant No. 81873619 and No. 81570663 to Aihua Zhang; The Key Clinical Program of Peking University Third Hospital under Grant BYSY2018024 to Lian He.

Author information

Authors and Affiliations

  1. Department of Nephrology, Peking University Third Hospital, 49 North Garden Rd, Haidian District, Beijing, 100191, China

    Wenhan Bao & Lian He

  2. Department of Nephrology, Xuanwu Hospital Capital Medical University, 45 Changchun Rd, Xicheng District, Beijing, 100053, China

    Aihua Zhang

Authors
  1. Wenhan Bao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lian He
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aihua Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by WB. The first draft of the manuscript was written by WB and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Lian He or Aihua Zhang.

Ethics declarations

Conflict of interest

The authors have no competing interests to declare that are relevant to the content of this article.

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. The study was approved by the Ethics Committee of Peking University Third Hospital (ethical approval number: M2018043). And, all patients signed the written informed consent.

Informed consent

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

Consent to participate

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

Consent for publication

The participant has consented to the submission of the article to the journal.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (XLS 62 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bao, W., He, L. & Zhang, A. Compensatory elevated serum intermedin levels are associated with increased vascular calcification in hemodialysis patients. Int Urol Nephrol 54, 3001–3007 (2022). https://doi.org/10.1007/s11255-022-03240-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-022-03240-2

Keywords

Search

Navigation