 |
 |
|
Home |
Current Issue |
Past Issues |
In the Clinic |
ACP Journal Club |
CME |
Collections |
Audio/Video |
Mobile |
Subscribe |
Tools |
Help |
ACP Online
|
| |||||||||||||||||||||||||||||||||||||||||||||||||
15 August 2006 | Volume 145 Issue 4 | Pages 237-246
Background: Cystatin C is an alternative measure of kidney function that may have prognostic importance among elderly persons who do not meet standard criteria for chronic kidney disease (estimated glomerular filtration rate [GFR]
Objective: To evaluate cystatin C as a prognostic biomarker for death, cardiovascular disease, and incident chronic kidney disease among elderly persons without chronic kidney disease.
Design: Cohort study.
Setting: The Cardiovascular Health Study, a population-based cohort recruited from 4 communities in the United States.
Participants: 4663 elderly persons.
Measurements: Measures of kidney function were creatinine-based estimated GFR by using the Modification of Diet in Renal Disease equation and cystatin C concentration. Outcomes were death, cardiovascular death, noncardiovascular death, heart failure, stroke, myocardial infarction, and incident chronic kidney disease during follow-up (median, 9.3 years).
Results: At baseline, 78% of participants did not have chronic kidney disease (estimated GFR
Limitations: Because this study did not directly measure GFR or albuminuria, the extent to which cystatin C may be influenced by nonrenal factors was not determined and participants with albuminuria might have been misclassified as having no kidney disease.
Conclusions: Among elderly persons without chronic kidney disease, cystatin C is a prognostic biomarker of risk for death, cardiovascular disease, and chronic kidney disease. In this setting, cystatin C seems to identify a "preclinical" state of kidney dysfunction that is not detected with serum creatinine or estimated GFR.
Editors' Notes
Context
Contribution
Cautions
Implications
—The Editors
Author and Article Information
From the San Francisco Veterans Affairs Medical Center and University of California, San Francisco, San Francisco, California; University of Washington, Seattle, Washington; Tufts-New England Medical Center, Boston, Massachusetts; Veterans Affairs Pittsburgh Healthcare System and University of Pittsburgh, Pittsburgh, Pennsylvania; Amgen Inc., Thousand Oaks, California; and University of Vermont College of Medicine, Burlington, Vermont.
Grant Support: Drs. Shlipak, Fried, and Katz are funded by R01 HL073208-01. Dr. Shlipak is also supported by the American Federation for Aging Research and National Institute on Aging (Paul Beeson Scholars Program), by the Robert Wood Johnson Foundation (Generalist Faculty Scholars Program), and by R01 DK066488. Drs. Sarnak, Fried, Shlipak, Siscovick, and Newman are also supported by R01 AG027002. Dr. Fried is supported by an Advanced Research Career Development award from the Office of Research and Development, Clinical Science Research and Development, U.S. Department of Veterans Affairs. The Cardiovascular Health Study (CHS) is supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, and N01-HC-15103 from the National Heart, Lung, and Blood Institute (NHLBI). A full list of participating CHS investigators and institutions can be found at http://www.chs-nhlbi.org.
Potential Financial Conflicts of Interest:Employment: C. Stehman-Breen (Amgen); Stock ownership or options (other than mutual funds): C. Stehman-Breen (Amgen).
Requests for Single Reprints: Michael G. Shlipak, MD, MPH, General Internal Medicine Section, Veterans Affairs Medical Center (111A1), 4150 Clement Street, San Francisco, CA 94121; e-mail, michael.shlipak{at}ucsf.edu.
Current Author Addresses: Dr. Shlipak: General Internal Medicine Section, Veterans Affairs Medical Center (111A1), 4150 Clement Street, San Francisco, CA 94121.
Dr. Katz: Collaborative Health Studies Coordinating Center, University of Washington, Box 354922, Building 29, Suite 310, 6200 NE 74th Street, Seattle, WA 98115.
Dr. Sarnak: Tufts-New England Medical Center, 750 Washington Street, Box 391, Boston, MA 02111.
Dr. Fried: Veterans Affairs Pittsburgh Healthcare System, University Drive, 111F-U, Pittsburgh, PA 15240.
Dr. Newman: Healthy Aging Research Program, Bellefield Professional Building, 130 North Bellefield Avenue, Room 532, Pittsburgh, PA 15213.
Dr. Stehman-Breen: Amgen, One Amgen Center Drive, Mailstop 38-3-C, Thousand Oaks, CA 91320.
Dr. Seliger: University of Maryland, N3W143, 22 South Greene Street, Baltimore, MD 21201.
Dr. Kestenbaum: Department of Medicine, Division of Nephrology, University of Washington, Veterans Affairs Puget Sound Health Care System, Mail Stop 111A, 1660 South Columbian Way, Seattle, WA 98108.
Drs. Psaty and Siscovick: Cardiovascular Health Research Unit, University of Washington, 1730 Minor Avenue, Suite 1360, Seattle, WA 98101-1448.
Dr. Tracy: University of Vermont College of Medicine, Colchester Research Facility, 208 South Park Drive, Suite 2, Colchester, VT 05446.
Author Contributions: Conception and design: M.G. Shlipak, M.J. Sarnak, A.B. Newman, C. Stehman-Breen, B. Kestenbaum, B. Psaty, R.P. Tracy, D.S. Siscovick.
Analysis and interpretation of the data: M.G. Shlipak, R. Katz, M.J. Sarnak, L.F. Fried, C. Stehman-Breen, S.L. Seliger, B. Psaty, D.S. Siscovick.
Drafting of the article: M.G. Shlipak, R. Katz, D.S. Siscovick.
Critical revision of the article for important intellectual content: M.G. Shlipak, R. Katz, M.J. Sarnak, L.F. Fried, A.B. Newman, C. Stehman-Breen, S.L. Seliger, B. Kestenbaum, B. Psaty, R.P. Tracy, D.S. Siscovick.
Final approval of the article: M.G. Shlipak, R. Katz, M.J. Sarnak, L.F. Fried, A.B. Newman, C. Stehman-Breen, S.L. Seliger, B. Kestenbaum, B. Psaty, R.P. Tracy, D.S. Siscovick.
Provision of study materials or patients: B. Psaty, R.P. Tracy, D.S. Siscovick.
Statistical expertise: R. Katz.
Obtaining of funding: M.G. Shlipak, R.P. Tracy.
Administrative, technical, or logistic support: M.G. Shlipak, R.P. Tracy.
Collection and assembly of data: R. Katz, B. Psaty, R.P. Tracy. ARTICLE
Cystatin C and Prognosis for Cardiovascular and Kidney Outcomes in Elderly Persons without Chronic Kidney Disease
60 mL/min per 1.73 m2). 60 mL/min per 1.73 m2) and mean cystatin C concentration, creatinine concentration, and estimated GFR were 1.0 mg/L, 79.6 µmol/L (0.9 mg/dL), and 83 mL/min per 1.73 m2, respectively. Cystatin C concentrations (per SD, 0.18 mg/L) had strong associations with death (hazard ratio, 1.33 [95% CI, 1.25 to 1.40]), cardiovascular death (hazard ratio, 1.42 [CI, 1.30 to 1.54]), noncardiovascular death (hazard ratio, 1.26 [CI, 1.17 to 1.36]), incident heart failure (hazard ratio, 1.28 [CI, 1.17 to 1.40]), stroke (hazard ratio, 1.22 [CI, 1.08 to 1.38]), and myocardial infarction (hazard ratio, 1.20 [CI, 1.06 to 1.36]) among these participants. Serum creatinine concentrations had much weaker associations with each outcome and only predicted cardiovascular death. Participants without chronic kidney disease who had elevated cystatin C concentrations (1.0 mg/L) had a 4-fold risk for progressing to chronic kidney disease after 4 years of follow-up compared with those with cystatin C concentrations less than 1.0 mg/L.
60 mL/min per 1.73 m2), increasing cystatin C concentration was associated with increased risks for death, stroke, myocardial infarction, heart failure, and progression to chronic kidney disease. Associations were much stronger for cystatin C than for creatinine.
Related articles in Annals:
This article has been cited by other articles:
|
|
 |
|
  F. W. Asselbergs, D. Mozaffarian, R. Katz, B. Kestenbaum, L. F. Fried, J. S. Gottdiener, M. G. Shlipak, and D. S. Siscovick Association of renal function with cardiac calcifications in older adults: the cardiovascular health study Nephrol. Dial. Transplant., October 7, 2008; (2008) gfn544v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sundelof, J. Arnlov, E. Ingelsson, J. Sundstrom, S. Basu, B. Zethelius, A. Larsson, M. C. Irizarry, V. Giedraitis, E. Ronnemaa, et al. Serum cystatin C and the risk of Alzheimer disease in elderly men Neurology, September 30, 2008; 71(14): 1072 - 1079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. T Fung, A. M Wilson, F. Zhang, N. Harris, K. A Edwards, J. W Olin, and J. P Cooke A biomarker panel for peripheral arterial disease Vascular Medicine, August 1, 2008; 13(3): 217 - 224. [Abstract] [PDF]
|
|
|
|
 |
|
 K. Potter, G. J. Hankey, D. J. Green, J. W. Eikelboom, and L. F. Arnolda Homocysteine or Renal Impairment: Which Is the Real Cardiovascular Risk Factor? Arterioscler. Thromb. Vasc. Biol., June 1, 2008; 28(6): 1158 - 1164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Weiner, H. Tighiouart, E. F. Elsayed, J. L. Griffith, D. N. Salem, and A. S. Levey Uric Acid and Incident Kidney Disease in the Community J. Am. Soc. Nephrol., June 1, 2008; 19(6): 1204 - 1211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. G. Jaar, R. Khatib, L. Plantinga, L. E. Boulware, and N. R. Powe Principles of Screening for Chronic Kidney Disease Clin. J. Am. Soc. Nephrol., March 1, 2008; 3(2): 601 - 609. [Full Text] [PDF]
|
|
|
|
|
|
J. H. Ix, R. Katz, B. Kestenbaum, L. F. Fried, H. Kramer, C. Stehman-Breen, and M. G. Shlipak Association of Mild to Moderate Kidney Dysfunction and Coronary Calcification J. Am. Soc. Nephrol., March 1, 2008; 19(3): 579 - 585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Pereg, A. Tirosh, T. Shochat, D. Hasdai, and for the Metabolic, Lifestyle and Nutrition Assessm Mild renal dysfunction associated with incident coronary artery disease in young males Eur. Heart J., January 2, 2008; 29(2): 198 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. H. de Boer, B. C. Astor, H. Kramer, W. Palmas, S. L. Seliger, M. G. Shlipak, D. S. Siscovick, M. Y. Tsai, and B. Kestenbaum Lipoprotein Abnormalities Associated with Mild Impairment of Kidney Function in the Multi-Ethnic Study of Atherosclerosis Clin. J. Am. Soc. Nephrol., January 1, 2008; 3(1): 125 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Odden, R. Scherzer, P. Bacchetti, L. A. Szczech, S. Sidney, C. Grunfeld, and M. G. Shlipak Cystatin C Level as a Marker of Kidney Function in Human Immunodeficiency Virus Infection: The FRAM Study Arch Intern Med, November 12, 2007; 167(20): 2213 - 2219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yoshida, H. Tomiyama, J. Yamada, Y. Koji, K. Shiina, M. Nagata, and A. Yamashina Relationships among Renal Function Loss within the Normal to Mildly Impaired Range, Arterial Stiffness, Inflammation, and Oxidative Stress Clin. J. Am. Soc. Nephrol., November 1, 2007; 2(6): 1118 - 1124. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Maahs, L. G. Ogden, A. Kretowski, J. K. Snell-Bergeon, G. L. Kinney, T. Berl, and M. Rewers Serum Cystatin C Predicts Progression of Subclinical Coronary Atherosclerosis in Individuals With Type 1 Diabetes Diabetes, November 1, 2007; 56(11): 2774 - 2779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. H. Chen, T. M. Sundt, D. J. Cook, D. M. Heublein, and J. C Burnett Jr Low Dose Nesiritide and the Preservation of Renal Function in Patients With Renal Dysfunction Undergoing Cardiopulmonary-Bypass Surgery: A Double-Blind Placebo-Controlled Pilot Study Circulation, September 11, 2007; 116(11_suppl): I-134 - I-138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Menon, M. G. Shlipak, X. Wang, J. Coresh, T. Greene, L. Stevens, J. W. Kusek, G. J. Beck, A. J. Collins, A. S. Levey, et al. Cystatin C as a Risk Factor for Outcomes in Chronic Kidney Disease Ann Intern Med, July 3, 2007; 147(1): 19 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Donahue, S. Stranges, K. Rejman, L. B. Rafalson, J. Dmochowski, and M. Trevisan Elevated Cystatin C Concentration and Progression to Pre-Diabetes: The Western New York Study Diabetes Care, July 1, 2007; 30(7): 1724 - 1729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Authors/Task Force Members:, G. Mancia, G. De Backer, A. Dominiczak, R. Cifkova, R. Fagard, G. Germano, G. Grassi, A. M. Heagerty, S. E. Kjeldsen, et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) Eur. Heart J., June 11, 2007; (2007) ehm236v1. [Full Text] [PDF]
|
|
|
|
 |
|
 K. V. Patel, T. B. Harris, M. Faulhaber, S. B. Angleman, S. Connelly, D. C. Bauer, L. H. Kuller, A. B. Newman, J. M. Guralnik, and for the Health, Aging, and Body Composition Study Racial variation in the relationship of anemia with mortality and mobility disability among older adults Blood, June 1, 2007; 109(11): 4663 - 4670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Rodondi, P. Yerly, A. Gabriel, W. F. Riesen, M. Burnier, F. Paccaud, and P. Bovet Microalbuminuria, but not cystatin C, is associated with carotid atherosclerosis in middle-aged adults Nephrol. Dial. Transplant., April 1, 2007; 22(4): 1107 - 1114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Singh, M. A. Whooley, J. H. Ix, S. Ali, and M. G. Shlipak Association of cystatin C and estimated GFR with inflammatory biomarkers: the Heart and Soul Study Nephrol. Dial. Transplant., April 1, 2007; 22(4): 1087 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. H. de Boer and M. W. Steffes Glomerular Filtration Rate and Albuminuria: Twin Manifestations of Nephropathy in Diabetes J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1036 - 1037. [Full Text] [PDF]
|
|
|
|
|
|
W. Van Biesen, D. De Bacquer, F. Verbeke, J. Delanghe, N. Lameire, and R. Vanholder The glomerular filtration rate in an apparently healthy population and its relation with cardiovascular mortality during 10 years Eur. Heart J., February 2, 2007; 28(4): 478 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Levey, L. A. Stevens, and T. Hostetter Automatic Reporting of Estimated Glomerular Filtration Rate--Just What the Doctor Ordered Clin. Chem., December 1, 2006; 52(12): 2188 - 2193. [Full Text] [PDF]
|
|
|
|
|
|
J. Coresh and B. Astor Decreased Kidney Function in the Elderly: Clinical and Preclinical, Neither Benign Ann Intern Med, August 15, 2006; 145(4): 299 - 301. [Full Text] [PDF]
|
|
Article
