Skip to main content

Advertisement

SpringerLink
Log in

Plasmatic osteopontin and vascular access dysfunction in hemodialysis patients: a cross-sectional, case–control study (The OSMOSIS Study)

  • Original Article
  • Published:
Journal of Nephrology Aims and scope Submit manuscript

Abstract

Background and aims

Despite close follow-up of patients with native arteriovenous fistulas (AVFs), up to 10% experience thrombosis each year. The OSMOSIS Study (Osteopontin as a Marker of Stenosis) tested the hypothesis that the systemic osteopontin level, a pro-inflammatory mediator related to vascular remodelling and intimal hyperplasia, increases in AVF stenosis, and may be used in clinical surveillance.

Methods

Our cross-sectional study compared the level of plasmatic osteopontin (pOPN) between patients with a well-functioning AVF (control group) and patients who required revision of their AVF due to stenosis (stenosis group). Blood samples were collected before dialysis (control group) or before intervention (stenosis group) from the AVF arm, and from the opposite arm as a within-subject control. pOPN level was measured by enzyme-linked immunosorbent assay.

Results

A total of 76 patients were included in the study. Baseline characteristics were similar between the groups (mean age, 70 years; men, 63%; AVF duration, 39 months), apart from prevalence of type 2 diabetes (T2D) (control group, 33%; stenosis group, 57%; p = 0.04). pOPN levels were similar between the AVF arm and the contralateral arm (551 ± 42 ng/mL vs. 521 ± 41 ng/mL, respectively, p = 0.11, paired t-test). Patients in the stenosis group displayed a higher pOPN level than patients in the control group (650.2 ± 59.8 ng/mL vs. 460.5 ± 61.2, respectively, p = 0.03; two-way ANOVA). T2D was not identified as an associated factor in a multivariate analysis (p = 0.50).

Conclusions

The level of pOPN in hemodialysis patients was associated with the presence of AVF stenosis requiring intervention. Thus, its potential as a diagnostic biomarker should be assessed in a vascular access surveillance program.

Graphic abstract

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

References

  1. Bylsma LC, Gage SM, Reichert H, Dahl SLM, Lawson JH (2017) Arteriovenous fistulae for haemodialysis: a systematic review and meta-analysis of efficacy and safety outcomes. Eur J Vasc Endovasc Surg 54:513–522

    Article  CAS  PubMed  Google Scholar 

  2. Lambie SH, Taal MW, Fluck RJ, McIntyre CW (2004) Analysis of factors associated with variability in haemodialysis adequacy. Nephrol Dial Transplant 19:406–412

    Article  PubMed  Google Scholar 

  3. Vascular Access Work Group (2006) Clinical practice guidelines for vascular access. Am J Kidney Dis 48(Suppl 1):S176-247

    Google Scholar 

  4. Tonelli M, Jindal K, Hirsch D, Taylor S, Kane C, Henbrey S (2001) Screening for subclinical stenosis in native vessel arteriovenous fistulae. J Am Soc Nephrol 12:1729–1733

    Article  PubMed  Google Scholar 

  5. Tessitore N, Bedogna V, Verlato G, Poli A (2014) Clinical access assessment. J Vasc Access 15:S20–S27

    Article  PubMed  Google Scholar 

  6. Rehman SU, Pupim LB, Shyr Y, Hakim R, Ikizler TA (1999) Intradialytic serial vascular access flow measurements. Am J Kidney Dis 34:471–477

    Article  CAS  PubMed  Google Scholar 

  7. Mudoni A, Caccetta F, Caroppo M, Musio F, Accogli A, Zacheo MD et al (2016) Echo color Doppler ultrasound: a valuable diagnostic tool in the assessment of arteriovenous fistula in hemodialysis patients. J Vasc Access 17:446–452

    Article  PubMed  Google Scholar 

  8. Han A, Min SK, Kim MS, Joo KW, Kim J, Ha J et al (2016) A Prospective, randomized trial of routine duplex ultrasound surveillance on arteriovenous fistula maturation. Clin J Am Soc Nephrol 11:1817–1824

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kumbar L, Karim J, Besarab A (2007) Surveillance and monitoring of dialysis access. Int J Nephrol 2012:649735

    Google Scholar 

  10. Scatena M, Liaw L, Giachelli CM (2007) Osteopontin: a multifunctional molecule regulating chronic inflammation and vascular disease. Arterioscler Thromb Vasc Biol 27:2302–2309

    Article  CAS  PubMed  Google Scholar 

  11. Liaw L, Almeida M, Hart CE, Schwartz SM, Giachelli CM (1994) Osteopontin promotes vascular cell adhesion and spreading and is chemotactic for smooth muscle cells in vitro. Circ Res 74:214–224

    Article  CAS  PubMed  Google Scholar 

  12. Golledge J, McCann M, Mangan S, Lam A, Karan M (2004) Osteoprotegerin and osteopontin are expressed at high concentrations within symptomatic carotid atherosclerosis. Stroke 35:1636–1641

    Article  CAS  PubMed  Google Scholar 

  13. He C, Choi HC, Xie Z (2010) Enhanced tyrosine nitration of prostacyclin synthase is associated with increased inflammation in atherosclerotic carotid arteries from type 2 diabetic patients. Am J Pathol 176:2542–2549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ishiyama M, Suzuki E, Katsuda J, Murase H, Tajima Y, Horikawa Y et al (2009) Associations of coronary artery calcification and carotid intima-media thickness with plasma concentrations of vascular calcification inhibitors in type 2 diabetic patients. Diabetes Res Clin Pract 85:189–196

    Article  CAS  PubMed  Google Scholar 

  15. Yilmaz KC, Bal UA, Karacaglar E, Okyay K, Aydinalp A, Yildirir A et al (2018) Plasma osteopontin concentration is elevated in patients with coronary bare metal stent restenosis. Acta Cardiol 73:69–74

    Article  PubMed  Google Scholar 

  16. Mohamadpour AH, Abdolrahmani L, Mirzaei H, Sahebkar A, Moohebati M, Ghorbani M et al (2015) Serum osteopontin concentrations in relation to coronary artery disease. Arch Med Res 46:112–117

    Article  CAS  PubMed  Google Scholar 

  17. Abdel-Azeez HA, Al-Zaky M (2010) Plasma osteopontin as a predictor of coronary artery disease: association with echocardiographic characteristics of atherosclerosis. J Clin Lab Anal 24:201–206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ohmori R, Momiyama Y, Taniguchi H, Takahashi R, Kusuhara M, Nakamura H et al (2003) Plasma osteopontin levels are associated with the presence and extent of coronary artery disease. Atherosclerosis 170:333–337

    Article  CAS  PubMed  Google Scholar 

  19. Kadoglou NP, Gerasimidis T, Golemati S, Kapelouzou A, Karayannacos PE, Liapis CD (2008) The relationship between serum levels of vascular calcification inhibitors and carotid plaque vulnerability. J Vasc Surg 47:55–62

    Article  PubMed  Google Scholar 

  20. Yan X, Sano M, Lu L, Wang W, Zhang Q, Zhang R et al (2010) Plasma concentrations of osteopontin, but not thrombin-cleaved osteopontin, are associated with the presence and severity of nephropathy and coronary artery disease in patients with type 2 diabetes mellitus. Cardiovasc Diabetol 9:70

    Article  PubMed  PubMed Central  Google Scholar 

  21. Pleskovic A, Santl Letonja M, Cokan Vujkovac A, Makuc J, Nikolajevic Starcevic J, Petrovic D (2018) Phosphoprotein 1 (osteopontin) gene (rs4754) affects markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus. Int Angiol 37:64–70

    Article  PubMed  Google Scholar 

  22. Kato R, Momiyama Y, Ohmori R, Tanaka N, Taniguchi H, Arakawa K et al (2006) High plasma levels of osteopontin in patients with restenosis after percutaneous coronary intervention. Arterioscler Thromb Vasc Biol 26:e1-2

    Article  CAS  PubMed  Google Scholar 

  23. Srivatsa SS, Fitzpatrick LA, Tsao PW, Reilly TM, Holmes DR Jr, Schwartz RS et al (1997) Selective alpha v beta 3 integrin blockade potently limits neointimal hyperplasia and lumen stenosis following deep coronary arterial stent injury: evidence for the functional importance of integrin alpha v beta 3 and osteopontin expression during neointima formation. Cardiovasc Res 36:408–428

    Article  CAS  PubMed  Google Scholar 

  24. Kang N, Ng CSH, Hu J, Qiu Z-B, Underwood MJ, Jeremy JY et al (2012) Role of osteopontin in the development of neointimal hyperplasia in vein grafts. Eur J Cardiothorac Surg 41:1384–1389

    Article  PubMed  Google Scholar 

  25. Hall MR, Yamamoto K, Protack CD, Tsuneki M, Kuwahara G, Assi R et al (2015) Temporal regulation of venous extracellular matrix components during arteriovenous fistula maturation. J Vasc Access 16:93–106

    Article  PubMed  Google Scholar 

  26. Abeles D, Kwei S, Stavrakis G, Zhang Y, Wang ET, Garcia-Cardena G (2006) Gene expression changes evoked in a venous segment exposed to arterial flow. J Vasc Surg 44:863–870

    Article  PubMed  Google Scholar 

  27. Woodside KJ, Bell S, Mukhopadhyay P, Repeck KJ, Robinson IT, Eckard AR et al (2018) Arteriovenous fistula maturation in prevalent hemodialysis patients in the United States: a national study. Am J Kidney Dis 71:793–801

    Article  PubMed  PubMed Central  Google Scholar 

  28. Zarkowsky DS, Arhuidese IJ, Hicks CW, Canner JK, Qazi U, Obeid T et al (2015) Racial/ethnic disparities associated with initial hemodialysis access. JAMA Surg 150:529–536

    Article  PubMed  Google Scholar 

  29. Allon M, Robbin ML, Umphrey HR, Young CJ, Deierhoi MH, Goodman J et al (2015) Preoperative arterial microcalcification and clinical outcomes of arteriovenous fistulas for hemodialysis. Am J Kidney Dis 66:84–90

    Article  PubMed  PubMed Central  Google Scholar 

  30. Smith GE, Gohil R, Chetter IC (2012) Factors affecting the patency of arteriovenous fistulas for dialysis access. J Vasc Surg 55:849–855

    Article  PubMed  Google Scholar 

  31. Nitta K, Ishizuka T, Horita S, Hayashi T, Ajiro A, Uchida K et al (2001) Soluble osteopontin and vascular calcification in hemodialysis patients. Nephron 89:455–458

    Article  CAS  PubMed  Google Scholar 

  32. Scialla JJ, Kao WH, Crainiceanu C, Sozio SM, Oberai PC, Shafi T et al (2014) Biomarkers of vascular calcification and mortality in patients with ESRD. Clin J Am Soc Nephrol 9:745–755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Al-Rubeaan K, Siddiqui K, Al-Ghonaim MA, Youssef AM, Al-Sharqawi AH, AlNaqeb D (2017) Assessment of the diagnostic value of different biomarkers in relation to various stages of diabetic nephropathy in type 2 diabetic patients. Sci Rep 7:2684

    Article  PubMed  PubMed Central  Google Scholar 

  34. Gordin D, Forsblom C, Panduru NM, Thomas MC, Bjerre M, Soro-Paavonen A et al (2014) Osteopontin is a strong predictor of incipient diabetic nephropathy, cardiovascular disease, and all-cause mortality in patients with type 1 diabetes. Diabetes Care 37:2593–2600

    Article  CAS  PubMed  Google Scholar 

  35. Zhang X, Chee WK, Liu S, Tavintharan S, Sum CF, Lim SC et al (2018) Association of plasma osteopontin with diabetic retinopathy in Asians with type 2 diabetes. Mol Vis 24:165–173

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Zwakenberg SR, van der Schouw YT, Schalkwijk CG, Spijkerman AMW, Beulens JWJ (2018) Bone markers and cardiovascular risk in type 2 diabetes patients. Cardiovasc Diabetol 17:45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lyu B, Banerjee T, Scialla JJ, Shafi T, Yevzlin AS, Powe NR et al (2018) Vascular calcification markers and hemodialysis vascular access complications. Am J Nephrol 48:330–338

    Article  CAS  PubMed  Google Scholar 

  38. Ulutas O, Taskapan MC, Dogan A, Baysal T, Taskapan H (2018) Vascular calcification is not related to serum fetuin-A and osteopontin levels in hemodialysis patients. Int Urol Nephrol 50:137–142

    Article  CAS  PubMed  Google Scholar 

  39. Olsson LF, Odselius R, Ribbe E, Hegbrant J (2001) Evidence of calcium phosphate depositions in stenotic arteriovenous fistulas. Am J Kidney Dis 38(2):377–383

    Article  CAS  PubMed  Google Scholar 

  40. Chou CY, Kuo HL, Yung YF, Liu YL, Huang CC (2006) C-reactive protein predicts vascular access thrombosis in hemodialysis patients. Blodd Purif 24(4):342–346

    Article  CAS  Google Scholar 

  41. Bertola A, Deveaux V, Bonnafous S, Rousseau D, Anty R, Wakkach A et al (2009) Elevated expression of osteopontin may be related to adipose tissue macrophage accumulation and liver steatosis in morbid obesity. Diabetes 58:125–133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kahles F, Findeisen HM, Bruemmer D (2014) Osteopontin: a novel regulator at the cross roads of inflammation, obesity and diabetes. Mol Metab 3:384–393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lund SA, Giachelli CM, Scatena M (2009) The role of osteopontin in inflammatory processes. J Cell Commun Signal 3:311–322

    Article  PubMed  PubMed Central  Google Scholar 

  44. Batko K, Krzanowski M, Gajda M, Dumnicka P, Fedak D, Woziwodzka K et al (2019) Endothelial injury is closely related to osteopontin and TNF receptor-mediated inflammation in end-stage renal disease. Cytokine 121:154729

    Article  CAS  PubMed  Google Scholar 

  45. Wu-Wong JR, Nakane M, Ma J, Ruan X, Kroeger PE (2007) Elevated phosphorus modulates vitamin D receptor-mediated gene expression in human vascular smooth muscle cells. Am J Physiol Renal Physiol 293:F1592–F1604

    Article  CAS  PubMed  Google Scholar 

  46. Son BK, Akishita M, Iijima K, Ogawa S, Arai T, Ishii H et al (2013) Thrombomodulin, a novel molecule regulating inorganic phosphate-induced vascular smooth muscle cell calcification. J Mol Cell Cardiol 56:72–80

    Article  CAS  PubMed  Google Scholar 

  47. Pedersen TX, Madsen M, Junker N, Christoffersen C, Vikesa J, Bro S et al (2013) Osteopontin deficiency dampens the pro-atherogenic effect of uraemia. Cardiovasc Res 98:352–359

    Article  CAS  PubMed  Google Scholar 

  48. Shimodaira T, Matsuda K, Uchibori T, Sugano M, Uehara T, Honda T (2018) Upregulation of osteopontin expression via the interaction of macrophages and fibroblasts under IL-1b stimulation. Cytokine 110:63–69

    Article  CAS  PubMed  Google Scholar 

  49. United States Renal Data System. 2018 USRDS annual data report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2018

  50. Daniele G, Winnier D, Mari A, Bruder J, Fourcaudot M, Pengou Z et al (2018) The potential role of the osteopontin-osteocalcin-osteoprotegerin triad in the pathogenesis of prediabetes in humans. Acta Diabetol 55:139–148

    Article  CAS  PubMed  Google Scholar 

  51. Kiefer FW, Zeyda M, Todoric J, Huber J, Geyeregger R, Weichhart T et al (2008) Osteopontin expression in human and murine obesity: extensive local up-regulation in adipose tissue but minimal systemic alterations. Endocrinology 149:1350–1357

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Dr Patricia Ferrari and Dr Eric Fontas for their advice regarding the design of the study, and Ms Abby Cuttriss for language editing of the manuscript.

Funding

This study was funded by the Centre Hospitalier Universitaire de Nice.

Author information

Authors and Affiliations

  1. Department of Emergency Medicine, Centre Hospitalier Universitaire de Nice, Nice, France

    Julie Contenti

  2. Centre Méditerranéen de Médecine Moléculaire, INSERM U1065, Université Côte d’Azur, Nice, France

    Julie Contenti, Réda Hassen-Khodja, Philippe Gual, Nathalie M. Mazure & Nirvana Sadaghianloo

  3. Department of Urology and Andrology and Renal Transplantation, Centre Hospitalier Universiatire de Nice, Nice, France

    Matthieu Durand

  4. Institute of Research on Cancer and Aging of Nice, INSERM U1081-CNRS, UMR 7284, Université Côte d’Azur, Nice, France

    Matthieu Durand

  5. Department of Nephrology and Hemodialysis, Centre Hospitalier Universitaire de Nice, Nice, France

    Sandor Vido

  6. Department of Vascular Surgery, Centre Hospitalier Universitaire de Nice, Hôpital Pasteur 1, 30 Ave de la voie Romaine, 06000, Nice, France

    Serge Declemy, Joseph Carboni, Sophie Bonnet, Réda Hassen-Khodja & Nirvana Sadaghianloo

  7. Clinical Chemistry Laboratory (J.R), Centre Hospitalier Universitaire de Nice, Nice, France

    Juliette Raffort

  8. Department of Clinical Research and Innovation, Centre Hospitalier Universitaire de Nice, Nice, France

    Sophie Bonnet

  9. Department of Anesthesiology, Centre Hospitalier Universitaire de Nice, Nice, France

    Christophe Koelsch

Authors
  1. Julie Contenti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthieu Durand
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sandor Vido
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Serge Declemy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Juliette Raffort
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joseph Carboni
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sophie Bonnet
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Christophe Koelsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Réda Hassen-Khodja
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Philippe Gual
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Nathalie M. Mazure
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Nirvana Sadaghianloo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JCo, RHK and NS designed the study; JCo, SV, SD, JR, SB and NS carried out experiments; MD, JCa, SB, CK, PG, NMM and NS analysed the data; JCo, NMM and NS made the figures and drafted the paper; MD, SV, SD, JCo, SB, CK, RHK and PG revised the paper; all authors approved the final version of the manuscript.

Corresponding author

Correspondence to Nirvana Sadaghianloo.

Ethics declarations

Conflict of interest

We declare no conflict of interest regarding this study.

Ethical approval

The study was approved by the national council on research (ANSM) and the institutional ethics committee (CPP Sud Méditerranée 1).

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 (DOCX 13 KB)

Supplementary file2 (PDF 55 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Contenti, J., Durand, M., Vido, S. et al. Plasmatic osteopontin and vascular access dysfunction in hemodialysis patients: a cross-sectional, case–control study (The OSMOSIS Study). J Nephrol 35, 527–534 (2022). https://doi.org/10.1007/s40620-021-01129-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40620-021-01129-4

Keywords

Search

Navigation