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Serum levels of cystatin C in patients with malignancy

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Abstract

Background

Serum levels of cystatin C have been proposed to be an ideal marker of the glomerular filtration rate (GFR). However, some reports have shown that serum levels of cystatin C increase independently of GFR. In this study, we evaluated the clinical utility of cystatin C in monitoring GFR, especially in patients with a malignancy.

Method

Study subjects consisted of 82 patients with a malignancy, 39 patients with a non-malignancy, 31 healthy volunteers, and 206 patients with various degrees of renal function. We measured serum cystatin C, β2-microglobulin (β2mG), and creatinine (CRE) levels in all patients. Serum CRP levels were measured in 21 patients with a malignancy and 28 patients with a non-malignancy whose creatinine clearance (Ccr) was ≥70 ml/min. Cystatin C, β2mG, and CRP were measured by immune nephelometry and CRE was measured by an enzyme assay.

Results

In patients with a malignancy, regression analysis yielded the equation: 1/cystatin C = 0.06 × Ccr + 0.710, correlation coefficient, r, of 0.33. The r was significantly lower than in patients with various degrees of renal function. There were no significant differences when the r performed on β2mG and CRE was compared between the same groups of patients. In 74 patients with a malignancy, in whom serum CRE levels were ≤1.1 mg/dl, increased levels of cystatin C were observed in 25 patients and increased levels of β2mG were observed in 39 patients. In comparing patients with a malignancy and a non-malignancy, the number of patients with an increased level of cystatin C, despite a Ccr ≥ 70 ml/min (8/33) or a CRE ≤ 1.1 mg/dl (13/41), was larger in the former group than the latter group, although the result was not statistically significant. Similarly, the number of patients with an increased level of β2mG, despite a Ccr ≥ 70 ml/min or a CRE ≤ 1.1 mg/dl was significantly larger in the former group compared to the latter group. Regression analysis between the serum levels of cystatin C and CRP in patients with a malignancy whose Ccr were ≥70 ml/min had a weak correlation (r = 0.31).

Conclusion

The results of our study suggest that the serum levels of cystatin C are not always a reliable marker of the GFR in patients with a malignancy, probably in relation to its nature as a cysteine protease inhibitor.

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References

  1. Barrett AJ, Davis MF, Grubb A. The place of human γ-trace (cystatin C) amongst the cystein protease inhibitors. Biochem Biophys Res Commun. 1984;120:631–6.

    Article  CAS  PubMed  Google Scholar 

  2. Grubb A, Lofberg H. Human γ trace, a basic microprotein; amino acid sequence and presence in the adenohypophysis. Proc Natl Acad Sci USA. 1982;79:3024–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Barret AJ, Fritz H, Grubb A, Isemura S, Jarvinen M, Katunuma N, et al. Nomenclature and classification of the protein homologous with chicken cystatin. Biochem J. 1986;236:312.

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Grubb A, Simonsen O, Sturtfelt G, Truedson L, Thysell H. Serum concentration of cystatin C, factor D and β2-microglobulin as a measure of glomerular filtration rate. Acta Med Scand. 1985;218:499–503.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. Hayashi T, Nitta K, Uchida K, Honda K, Kobayashi H, Kawashima A, et al. Clinical measurement of serum cystatin C as a marker of glomerular filtration rate. Clin Exp Nephrol. 2000;4:133–6.

    Article  CAS  Google Scholar 

  8. Kos J, Štabuc B, Cimerman N, Brunner N. Serum cystatin C, a new marker of glomerular filtration rate, is increased during malignant progression. Clin Chem. 1998;44:2556–7.

    CAS  PubMed  Google Scholar 

  9. Kos J, Štabuc B, Schweigen A, Krašovec M, Cimerman N, Kopitar-Jarala N, et al. Cathepsins B, H, and L and their inhibitors stefin A and cystatin C in sera of melanoma patients. Clin Cancer Res. 1997;3:1815–22.

    CAS  PubMed  Google Scholar 

  10. Sokol JP, Schiemann WP. Cystatin C antagonizes transforming growth factor beta signaling in normal and cancer cells. Mol Cancer Res. 2004;2:183–95.

    CAS  PubMed  Google Scholar 

  11. Demirtas S, Akan O, Can M, Elmali E, Akan H. Cystatin C can be affected by nonrenal factors: a preliminary study on leukemia. Clin Biochem. 2006;39:115–8.

    Article  CAS  PubMed  Google Scholar 

  12. Knight EL, Verhave JC, Spiegelman D, Hillege HL, Zeew DD, 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 

  13. Erlandsen EJ, Rander E, Kristensen JH. Evaluation of the Dade Behring N Latex Cystatin C assay on the Dade Behring nephelometer II System. Scand J Clin Lab Invest. 1999;59:1–8.

    Article  CAS  PubMed  Google Scholar 

  14. Ohara T, Nakai K, Orisaka M, Ito C, Saito K, Ito Y. A trial for establishing reference intervals of serum cystatin C in normal individuals. Jpn J Med Pharm Sci. 2000;43:835–44.

    CAS  Google Scholar 

  15. Page MK, Bukki J, Luppa P, Neumeier D. Clinical value of cystatin C determination. Clin Chim Acta. 2000;297:67–72.

    Article  CAS  PubMed  Google Scholar 

  16. Nishikawa H, Ozaki Y, Nakanishi T, Blomgren K, Tada T, Arakawa A, et al. The role of cathepsin B and cystatin C in the mechanism of invasion by ovarian cancer. Gynecol Oncol. 2004;92:881–6.

    Article  CAS  PubMed  Google Scholar 

  17. Zore I, Krašovec M, Cimerman N, Kuhelj R, Werle B, Nielsen HJ, et al. Cathepsin B/cystatin C complex levels in sera from patients with lung and colorectal cancer. Biol Chem. 2001;382:805–10.

    Article  CAS  PubMed  Google Scholar 

  18. Colle A, Tavera C, Prevot D, Leung-Tack J, Thomas Y, Manuel Y, et al. Cystatin C levels in sera of patients with human immunodeficiency virus infection. J Immnoassay. 1992;13:47–60.

    Article  CAS  Google Scholar 

  19. Finney H, Williams AH, Price CP. Serum cystatin C in patients with myeloma. Clin Chem Acta. 2001;309:1–6.

    Article  CAS  Google Scholar 

  20. Werle B, Sauckel K, Nathanson CM, Bjarnadottir M, Spiess E, Ebert W, et al. Cystatin C, E/M, and F in human pleural fluids of patients with neoplastic and inflammatory lung disorders. Biol Chem. 2003;384:281–7.

    Article  CAS  PubMed  Google Scholar 

  21. Reed CH. Diagnostic applications of cystatin C. Br J Biomed Sci. 2000;57:323–9.

    CAS  PubMed  Google Scholar 

  22. Hansen T, Petrow PK, Gaumann A, Keyszer G, Brauer R, Kriegsmann J. Synovial giant cells in rheumatoid arthritis:expression of cystatin C, but not cathepsin B. Exp Toxicol Pathol. 2000;52:312–6.

    Article  CAS  PubMed  Google Scholar 

  23. Curhan G. Cystatin C:a marker of renal function or something more. Clin Chem. 2005;51:293–4.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Keiko Nakai.

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Nakai, K., Kikuchi, M., Fujimoto, K. et al. Serum levels of cystatin C in patients with malignancy. Clin Exp Nephrol 12, 132–139 (2008). https://doi.org/10.1007/s10157-008-0043-8

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  • DOI: https://doi.org/10.1007/s10157-008-0043-8

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