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Serum cystatin C as a predictor for cardiovascular events in end-stage renal disease patients at the initiation of dialysis

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Abstract

Background

There has been no study to investigate whether cystatin C could predict cardiovascular events in incident dialysis patients. We aimed to delineate the role of serum cystatin C and cystatin C-based estimated glomerular filtration rate (eGFRcysC) for prediction of cardiovascular events.

Methods

This study included 66 end-stage renal disease patients who survived for >3 months after the start of dialysis, and serum cystain C levels were measured at the point of dialysis initiation.

Results

Serum cystatin C was correlated with blood urea nitrogen (r = 0.537, p < 0.001), serum creatinine (r = 0.480, p < 0.001) and smoking (r = 0.284, p = 0.021). Cystatin C was inversely correlated with age (r = −0.316, p = 0.01) and eGFRCr by modification of diet in renal disease (r = −0.533, p < 0.001). Kaplan–Meier analysis for cardiovascular events revealed that patients in the group with lower cystatin C levels (<4.14 mg/L) had a better event-free survival rate than patients in the group with higher cystatin C levels (≥4.14 mg/L) (p = 0.039). In univariate analysis, cystatin C (hazard ratio (HR) 2.62, p = 0.011) and eGFRcysC (HR 0.64, p = 0.004) were significant factors for the prediction of cardiovascular events. After multivariate adjustment, serum cystatin C and eGFRcysC were independent determinants of cardiovascular events (HR 3.952, p = 0.001 and HR 0.640, p = 0.004, respectively).

Conclusion

Serum cystatin C might be an independent marker of cardiovascular events in incident dialysis patients. Furthermore, eGFRcysC based on measured serum cystatin C could have a new role in predicting cardiovascular events beyond the estimation of true GFR.

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References

  1. Levey AS. Controlling the epidemic of cardiovascular disease in chronic renal disease: where do we start? Am J Kidney Dis. 1998;32:S5–13.

    Article  PubMed  CAS  Google Scholar 

  2. Boutouyrie P, Tropeano AI, Asmar R, Gautier I, Benetos A, Lacolley P, et al. Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: a longitudinal study. Hypertension. 2002;39:10–5.

    Article  PubMed  CAS  Google Scholar 

  3. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001;37:1236–41.

    Article  PubMed  CAS  Google Scholar 

  4. Cruickshank K, Riste L, Anderson SG, Wright JS, Dunn G, Gosling RG. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function. Circulation. 2002;106:2085–90.

    Article  PubMed  Google Scholar 

  5. Konings CJ, Hermans M, Kooman JP, Meinders JM, Hoeks AP, van der Sande FM, et al. Arterial stiffness and renal replacement therapy. Perit Dial Int. 2004;24:318–22.

    PubMed  Google Scholar 

  6. Klassen PS, Lowrie EG, Reddan DN, DeLong ER, Coladonato JA, Szczech LA, et al. Association between pulse pressure and mortality in patients undergoing maintenance hemodialysis. JAMA. 2002;287:1548–55.

    Article  PubMed  Google Scholar 

  7. Blacher J, Safar ME, Guerin AP, Pannier B, Marchais SJ, London GM. Aortic pulse wave velocity index and mortality in end-stage renal disease. Kidney Int. 2003;63:1852–60.

    Article  PubMed  Google Scholar 

  8. Song SH, Kwak IS, Kim YJ, Lee HS, Rhee H, Lee DW, et al. Serum cystatin C is related to pulse wave velocity even in subjects with normal serum creatinine. Hypertens Res. 2008;31:1895–902.

    Article  PubMed  CAS  Google Scholar 

  9. Madero M, Wassel CL, Peralta CA, Najjar SS, Sutton-Tyrrell K, Fried L, et al. Cystatin C associates with arterial stiffness in older adults. J Am Soc Nephrol. 2009;20:1086–93.

    Article  PubMed  CAS  Google Scholar 

  10. Laterza OF, Price CP, Scott MG. Cystatin C: an improved estimator of glomerular filtration rate? Clin Chem. 2002;48:699–707.

    PubMed  CAS  Google Scholar 

  11. Seronie-Vivien S, Delanaye P, Pieroni L, Mariat C, Froissart M, SFBC “Biology of renal function and renal failure” working group. Cystatin C: current position and future prospects. Clin Chem Lab Med. 2008;46:1664–86.

    Article  PubMed  CAS  Google Scholar 

  12. 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  PubMed  CAS  Google Scholar 

  13. Shlipak MG, Katz R, Fried LF, Jenny NS, Stehman-Breen CO, Newman AB, et al. Cystatin-C and mortality in elderly persons with heart failure. J Am Coll Cardiol. 2005;45:268–71.

    Article  PubMed  CAS  Google Scholar 

  14. Astor BC, Levey AS, Stevens LA, Van Lente F, Selvin E, Coresh J. Method of glomerular filtration rate estimation affects prediction of mortality risk. J Am Soc Nephrol. 2009;20:2214–22.

    Article  PubMed  Google Scholar 

  15. Menon V, Shlipak MG, Wang X, Coresh J, Greene T, Stevens L, et al. Cystatin C as a risk factor for outcomes in chronic kidney disease. Ann Intern Med. 2007;147:19–27.

    PubMed  Google Scholar 

  16. Peralta CA, Katz R, Sarnak MJ, Ix J, Fried LF, De Boer I, et al. Cystatin C identifies chronic kidney disease patients at higher risk for complications. J Am Soc Nephrol. 2011;22:147–55.

    Article  PubMed  Google Scholar 

  17. Rule AD, Lieske JC. Cystatin C is more than GFR, and this may be a good thing. J Am Soc Nephrol. 2011;22:795–7.

    Article  PubMed  Google Scholar 

  18. Wiesli P, Schwegler B, Spinas GA, Schmid C. Serum cystatin C is sensitive to small changes in thyroid function. Clin Chim Acta. 2003;338:87–90.

    Article  PubMed  CAS  Google Scholar 

  19. Risch L, Herklotz R, Blumberg AR. Effects of glucocorticoid immunosuppression on serum cystatin C concentrations in renal transplant patients. Clin Chem. 2001;47:2055–9.

    PubMed  CAS  Google Scholar 

  20. Myers GL, Miller WG, Coresh J, Fleming J, Greenberg N, Greene T, et al. Recommendations for improving serum creatinine measurement: a report from the laboratory working group of the national kidney disease education program. Clin Chem. 2006;52:5–18.

    Article  PubMed  CAS  Google Scholar 

  21. Stevens LA, Coresh J, Schmid CH, Feldman HI, Froissart M, Kusek J, et al. Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis. 2008;51:395–406.

    Article  PubMed  CAS  Google Scholar 

  22. Shlipak MG, Katz R, Sarnak MJ, Fried LF, Newman AB, Stehman-Breen C, et al. Cystatin C and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease. Ann Intern Med. 2006;145:237–46.

    PubMed  CAS  Google Scholar 

  23. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification. Am J Kidney Dis. 2002;39:S1–266.

    Article  Google Scholar 

  24. Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis. 2002;40:221–6.

    Article  PubMed  CAS  Google Scholar 

  25. 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  PubMed  CAS  Google Scholar 

  26. Kottgen A, Selvin E, Stevens LA, Levey AS, Van Lente F, Coresh J. Serum cystatin C in the United States: the Third National Health and Nutrition Examination Survey (NHANES III). Am J Kidney Dis. 2008;51:385–94.

    Article  PubMed  CAS  Google Scholar 

  27. Odden MC, Tager IB, Gansevoort RT, Bakker SJ, Katz R, Fried LF, et al. Age and cystatin C in healthy adults: a collaborative study. Nephrol Dial Transplant. 2010;25:463–9.

    Article  PubMed  CAS  Google Scholar 

  28. 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  PubMed  CAS  Google Scholar 

  29. Okura T, Jotoku M, Irita J, Enomoto D, Nagao T, Desilva VR, et al. Association between cystatin C and inflammation in patients with essential hypertension. Clin Exp Nephrol. 2010;14:584–8.

    Article  PubMed  CAS  Google Scholar 

  30. 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  PubMed  CAS  Google Scholar 

  31. Yashiro M, Kamata T, Segawa H, Kadoya Y, Murakami T, Muso E. Comparisons of cystatin C with creatinine for evaluation of renal function in chronic kidney disease. Clin Exp Nephrol. 2009;13:598–604.

    Article  PubMed  CAS  Google Scholar 

  32. Muntner P, Winston J, Uribarri J, Mann D, Fox CS. Overweight, obesity, and elevated serum cystatin C levels in adults in the United States. Am J Med. 2008;121:341–8.

    Article  PubMed  CAS  Google Scholar 

  33. Macdonald J, Marcora S, Jibani M, Roberts G, Kumwenda M, Glover R, et al. GFR estimation using cystatin C is not independent of body composition. Am J Kidney Dis. 2006;48:712–9.

    Article  PubMed  CAS  Google Scholar 

  34. Ma YC, Zuo L, Chen JH, Luo Q, Yu XQ, Li Y, Chinese eGFR Investigation Collaboration, et al. Improved GFR estimation by combined creatinine and cystatin C measurements. Kidney Int. 2007;72:1535–42.

    Article  PubMed  CAS  Google Scholar 

  35. Peralta CA, Katz R, Sarnak MJ, Ix J, Fried LF, De Boer I, et al. Cystatin C identifies chronic kidney disease patients at higher risk for complications. J Am Soc Nephrol. 2011;22:147–55.

    Article  PubMed  Google Scholar 

  36. Taglieri N, Koenig W, Kaski JC. Cystatin C and cardiovascular risk. Clin Chem. 2009;55:1932–43.

    Article  PubMed  CAS  Google Scholar 

  37. Mathisen UD, Melsom T, Ingebretsen OC, Jenssen T, Njølstad I, Solbu MD, et al. Estimated GFR associates with cardiovascular risk factors independently of measured GFR. J Am Soc Nephrol. 2011;22:927–37.

    Article  PubMed  Google Scholar 

  38. Bengtsson E, To F, Håkansson K, Grubb A, Brånén L, Nilsson J, et al. Lack of the cysteine protease inhibitor cystatin C promotes atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2005;25:2151–6.

    Article  PubMed  CAS  Google Scholar 

  39. Lafarge JC, Naour N, Clément K, Guerre-Millo M. Cathepsins and cystatin C in atherosclerosis and obesity. Biochimie. 2010;92:1580–6.

    Article  PubMed  CAS  Google Scholar 

  40. Imai A, Komatsu S, Ohara T, et al. Serum cystatin C is associated with early stage coronary atherosclerotic plaque morphology on multidetector computed tomography. Atherosclerosis. 2011;218:350–5.

    Article  PubMed  CAS  Google Scholar 

  41. Maahs DM, Ogden LG, Kretowski A, et al. Serum cystatin C predicts progression of subclinical coronary atherosclerosis in individuals with type 1 diabetes. Diabetes. 2007;56:5774–9.

    Article  Google Scholar 

  42. Koenig W, Twardella D, Brenner H, Rothenbacher D. Plasma concentrations of cystatin C in patients with coronary heart disease and risk for secondary cardiovascular events: more than simply a marker of glomerular filtration rate. Clin Chem. 2005;51:321–7.

    Article  PubMed  CAS  Google Scholar 

  43. Luc G, Bard JM, Lesueur C, et al. Plasma cystatin-C and development of coronary heart disease: the PRIME Study. Atherosclerosis. 2006;185:375–80.

    Article  PubMed  CAS  Google Scholar 

  44. Wang J, Sim AS, Wang XL, et al. Relations between markers of renal function, coronary risk factors and the occurrence and severity of coronary artery disease. Atherosclerosis. 2008;197:853–9.

    Article  PubMed  CAS  Google Scholar 

  45. Jernberg T, Lindahl B, James S, et al. Cystatin C: a novel predictor of outcome in suspected or confirmed non-ST-elevation acute coronary syndrome. Circulation. 2004;110:2342–8.

    Article  PubMed  CAS  Google Scholar 

  46. Bassand JP, Hamm CW, Ardissino D, Task Force for Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of European Society of Cardiology, et al. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Eur Heart J. 2007;28:1598–660.

    Article  PubMed  CAS  Google Scholar 

  47. Samouilidou EC, Grapsa E. Relationship of serum cystatin C with C-reactive protein and apolipoprotein A1 in patients on hemodialysis. Ren Fail. 2008;30:711–5.

    Article  PubMed  CAS  Google Scholar 

  48. Koc M, Batur MK, Karaarslan O, Abali G. Clinical utility of serum cystatin C in predicting coronary artery disease. Cardiol J. 2010;17:374–80.

    PubMed  Google Scholar 

  49. Evangelopoulos AA, Vallianou NG, Bountziouka V, et al. Association between serum cystatin C, monocytes and other inflammatory markers. Intern Med J. 2011;. doi:10.1111/j.1445-5994.2011.02500.x.

    Google Scholar 

  50. Ferraro S, Marano G, Biganzoli EM, Boracchi P, Bongo AS. Prognostic value of cystatin C in acute coronary syndromes: enhancer of atherosclerosis and promising therapeutic target. Clin Chem Lab Med. 2011;49:1397–404.

    Article  PubMed  CAS  Google Scholar 

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Conflict of interest

The authors have declared that no conflict of interest exists.

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Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, Pusan National University Hospital School of Medicine, Gudeok-ro 179, Seo-gu, Busan, Republic of Korea

    Min Ji Shin, Sang Heon Song, Ihm Soo Kwak, Soo Bong Lee, Dong Won Lee, Eun Young Seong, Il Young Kim, Harin Rhee & Naria Lee

  2. Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea

    Sang Heon Song, Ihm Soo Kwak, Eun Young Seong & Harin Rhee

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  1. Min Ji Shin
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Correspondence to Sang Heon Song.

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Shin, M.J., Song, S.H., Kwak, I.S. et al. Serum cystatin C as a predictor for cardiovascular events in end-stage renal disease patients at the initiation of dialysis. Clin Exp Nephrol 16, 456–463 (2012). https://doi.org/10.1007/s10157-011-0583-1

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  • DOI: https://doi.org/10.1007/s10157-011-0583-1

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