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Association between cystatin C and inflammation in patients with essential hypertension

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Abstract

Background

Serum cystatin C is not only a marker of renal function but also acts as an independent risk factor for cardiovascular damage, heart failure, and death. It is known that the initiation and progression of these cardiovascular events contributes to renal dysfunction and chronic inflammation. In this study, we investigated the relationship between cystatin C and proinflammatory cytokines.

Methods

Eighty-eight patients with essential hypertension participated in the study, which involved measuring proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and C reactive protein (CRP).

Results

Positive correlations were detected between cystatin C and estimated glomerular filtration rate (eGFR) (r = −0.503, p < 0.001), systolic blood pressure (r = −0.246, p = 0.034), and pulse pressure (r = −0.295, p = 0.010). In contrast, serum creatinine correlated only with eGFR (r = −0.755, p < 0.001) and eGFR correlated only with age (r = −0.339, p = 0.001) and not with the other clinical parameters, whereas cystatin C also correlated with log natural (ln) IL-6 (r = −0.247, p = 0.033) and ln TNF-α (r = −0.405, p < 0.001) but not with CRP (r = −0.188, p = 0.108). In contrast, plasma creatinine and eGFR did not correlate with any of these proinflammatory cytokines. Stepwise regression analysis showed that ln TNF-α, eGFR and pulse pressure were independent determinants of serum cystatin C concentration.

Conclusion

This study showed that cystatin C is a marker of inflammation as well as renal function.

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References

  1. Newman DJ, Thakkar H, Edwards RG, Wilkie M, White T, Grubb AO, et al. Serum cystatin C measured by automated immunoassay: a more sensitive marker of changes in GFR than serum creatinine. Kidney Int. 1995;47:312–8.

    Article  CAS  PubMed  Google Scholar 

  2. Kyhse-Andersen J, Schmidt C, Nordin G, Andersson B, Nilsson-Ehle P, Lindström V, et al. Serum cystatin C, determined by a rapid, automated particle-enhanced turbidimetric method, is a better marker than serum creatinine for glomerular filtration rate. Clin Chem. 1994;40:1921–6.

    CAS  PubMed  Google Scholar 

  3. Abrahamson M, Olafsson I, Palsdottir A, Ulvsbäck M, Lundwall A, Jensson O, et al. Structure and expression of the human cystatin C gene. Biochem J. 1990;268:287–94.

    CAS  PubMed  Google Scholar 

  4. Simonsen O, Grubb A, Thysell H. The blood serum concentration of cystatin C (gamma-trace) as a measure of the glomerular filtration rate. Scand J Clin Lab Invest. 1985;45:97–101.

    Article  CAS  PubMed  Google Scholar 

  5. Tian S, Kusano E, Ohara T, Tabei K, Itoh Y, Kawai T, et al. Cystatin C measurement and its practical use in patients with various renal diseases. Clin Nephrol. 1997;48:104–8.

    CAS  PubMed  Google Scholar 

  6. Grubb A, Simonsen O, Sturfelt G, Truedsson L, Thysell H. Serum concentration of cystatin C, factor D and b2-microglobulin as a measure of glomerular filtration rate. Acta Med Scand. 1985;218:499–503.

    Article  CAS  PubMed  Google Scholar 

  7. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340:115–26.

    Article  CAS  PubMed  Google Scholar 

  8. Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868–74.

    Article  CAS  PubMed  Google Scholar 

  9. Lacy F, O’Connor DT, Schmid-Schönbein GW. Plasma hydrogen peroxide production in hypertensives and normotensive subjects at genetic risk of hypertension. J Hypertens. 1998;16:291–303.

    Article  CAS  PubMed  Google Scholar 

  10. Bautista LE, Vera LM, Arenas IA, Gamarra G. Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-alpha) and essential hypertension. J Hum Hypertens. 2005;19:149–54.

    Article  CAS  PubMed  Google Scholar 

  11. Chae CU, Lee RT, Rifai N, Ridker PM. Blood pressure and inflammation in apparently healthy men. Hypertension. 2001;38:399–403.

    CAS  PubMed  Google Scholar 

  12. Bautista LE, López-Jaramillo P, Vera LM, Casas JP, Otero AP, Guaracao AI. Is C-reactive protein an independent risk factor for essential hypertension? J Hypertens. 2001;19:857–61.

    Article  CAS  PubMed  Google Scholar 

  13. O’Hare AM, Newman AB, Katz R, Fried LF, Stehman-Breen CO, Seliger SL, et al. Cystatin C and incident peripheral arterial disease events in the elderly: results from the Cardiovascular Health Study. Arch Intern Med. 2005;165:2666–70.

    Article  PubMed  Google Scholar 

  14. Ix JH, Shlipak MG, Chertow GM, Whooley MA. Association of cystatin C with mortality, cardiovascular events, and incident heart failure among persons with coronary heart disease. data from the Heart and Soul Study. Circulation. 2007;115:173–9.

    Article  CAS  PubMed  Google Scholar 

  15. Saenak MJ, Katz R, Stehman-Breen CO, Fried LF, Jenny NS, Psaty BM, et al. Cystatin C concentration as a risk factor for heart failure in older adults. Ann Intern Med. 2005;142:497–505.

    Google Scholar 

  16. Shlipak MG, Sarnak MJ, Katz R, Fried LF, Seliger SL, Newman AB, et al. Cystatin C and the risk of death and cardiovascular events among elderly persons. N Engl J Med. 2005;352:2049–60.

    Article  CAS  PubMed  Google Scholar 

  17. Watanabe S, Okura T, Miyoshi K, Fukuoka T, Hiwada K, Higaki J. Serum cystatin C level is a marker of end-organ damage in patients with essential hypertension. Hypertens Res. 2003;26:895–9.

    Article  CAS  PubMed  Google Scholar 

  18. Keller CR, Odden MC, Fried LF, Newman AB, Angleman S, Green CA, et al. Kidney function and markers of inflammation in elderly persons without chronic kidney disease: the health, aging, and body composition study. Kidney Int. 2008;71:239–44.

    Article  Google Scholar 

  19. Watanabe S, Okura T, Kurata M, Irita J, Manabe S, Miyoshi K, et al. Valsartan reduces serum cystatin C and the renal vascular resistance in patients with essential hypertension. Clin Exp Hypertens. 2006;28:451–61.

    Article  CAS  PubMed  Google Scholar 

  20. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340:448–54.

    Article  CAS  PubMed  Google Scholar 

  21. Blake GJ, Ridker PM. Novel clinical markers of vascular wall inflammation. Circ Res. 2001;89:763–71.

    Article  CAS  PubMed  Google Scholar 

  22. Okura T, Watanabe S, Miyoshi K, Fukuoka T, Higaki J. Intrarenal and carotid hemodynamics in patients with essential hypertension. Am J Hypertens. 2004;17:240–4.

    Article  PubMed  Google Scholar 

  23. Kestenbaum B, Rudser KD, de Boer IH, Peralta CA, Fried LF, Shlipak MG, et al. Differences in kidney function and incident hypertension: the multi-ethnic study of atherosclerosis. Ann Intern Med. 2008;148:501–8.

    PubMed  Google Scholar 

  24. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–305.

    Article  CAS  PubMed  Google Scholar 

  25. Herbelin A, Ureña P, Nguyen AT, Zingraff J, Descamps-Latscha B. Elevated circulating levels of interleukin-6 in patients with chronic renal failure. Kidney Int. 1991;39:954–60.

    Article  CAS  PubMed  Google Scholar 

  26. Pereira BJ, Shapiro L, King AJ, Falagas ME, Strom JA, Dinarello CA. Plasma levels of IL-1 beta, TNF alpha and their specific inhibitors in undialyzed chronic renal failure, CAPD and hemodialysis. Kidney Int. 1994;45:890–6.

    Article  CAS  PubMed  Google Scholar 

  27. Owen WF, Lowrie EG. C-reactive protein as an outcome predictor for maintenance hemodialysis patients. Kidney Int. 1998;54:627–36.

    Article  CAS  PubMed  Google Scholar 

  28. Frendéus KH, Wallin H, Janciauskiene S, Abrahamson M. Macrophage responses to interferon-gamma are dependent on cystatin C levels. Int J Biochem Cell Biol. 2009;41:2262–9.

    Article  PubMed  Google Scholar 

  29. Knight EL, Verhave JC, Spiegelman D, Hillege HL, de Zeeuw D, Curhan GC, et al. Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement. Kidney Int. 2004;65:1416–21.

    Article  CAS  PubMed  Google Scholar 

  30. Singh D, Whooley MA, Ix JH, Ali S, Shlipak MG. Association of cystatin C and estimated GFR with inflammatory biomarkers: the Heart and Soul Study. Nephrol Dial Transplant. 2007;22:1087–92.

    Article  CAS  PubMed  Google Scholar 

  31. Stevens LA, Schmid CH, Greene T, Li L, Beck GJ, Joffe MM, et al. Factors other than glomerular filtration rate affect serum cystatin C levels. Kidney Int. 2009;75:652–60.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a Grant-in-Aid Scientific Research (C) awarded to TO by the Japan Society for the Promotion of Science (22590912).

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Authors and Affiliations

  1. Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine, Toon, Ehime, 791-0295, Japan

    Takafumi Okura, Masanori Jotoku, Jun Irita, Daijiro Enomoto, Tomoaki Nagao, Veena Rasika Desilva, Shiho Yamane, Zuowei Pei, Ken-ichi Miyoshi & Jitsuo Higaki

  2. Department of Research and Development, Ikagaku Co., Ltd., Hazukashi, Fushimi-ku, Kyoto, Kyoto, 612-8486, Japan

    Shiho Kojima, Yasuyuki Hamano & Shinichi Mashiba

  3. Department of Pathology, Division of Pathogenomics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan

    Mie Kurata

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  1. Takafumi Okura
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  2. Masanori Jotoku
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Correspondence to Takafumi Okura.

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Okura, T., Jotoku, M., Irita, J. et al. Association between cystatin C and inflammation in patients with essential hypertension. Clin Exp Nephrol 14, 584–588 (2010). https://doi.org/10.1007/s10157-010-0334-8

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  • DOI: https://doi.org/10.1007/s10157-010-0334-8

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