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Cystatin C and Prognosis for Cardiovascular and Kidney Outcomes in Elderly Persons without Chronic Kidney Disease

Michael G. Shlipak, MD, MPH; Ronit Katz, PhD; Mark J. Sarnak, MD; Linda F. Fried, MD, MPH; Anne B. Newman, MD, MPH; Catherine Stehman-Breen, MD, MS; Stephen L. Seliger, MD; Brian Kestenbaum, MD; Bruce Psaty, MD, PhD; Russell P. Tracy, PhD; and David S. Siscovick, MD, MPH
[+] Article and Author 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@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.


Ann Intern Med. 2006;145(4):237-246. doi:10.7326/0003-4819-145-4-200608150-00003
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Among the 4663 participants in our study, 1004 (22%) had chronic kidney disease and 3659 (78%) had no chronic kidney disease. Among participants with chronic kidney disease, the mean cystatin C concentration, creatinine concentration, and estimated GFR were 1.5 mg/L, 123.8 µmol/L (1.4 mg/dL), and 50 mL/min per 1.73 m2, respectively. Among those without chronic kidney disease, the mean values were 1.0 mg/L, 79.6 µmol/L (0.9 mg/dL), and 83 mL/min per 1.73 m2, respectively. The Pearson correlations (r) of cystatin C with creatinine and with estimated GFR were 0.81 and −0.75 (both P < 0.001), respectively, among persons with chronic kidney disease and 0.38 and −0.46 (both P < 0.001), respectively, among persons without chronic kidney disease. These correlations with cystatin C were significantly stronger among the subgroup with chronic kidney disease than among the subgroup without chronic kidney disease (P < 0.001 for both correlations by the Fisher exact test). Figure 1 shows the distributions of creatinine and cystatin C concentrations among CHS participants without chronic kidney disease.

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Figures

Grahic Jump Location
Figure 1.
Distribution of creatinine concentration (top) and cystatin C concentration (bottom) in elderly participants without chronic kidney disease.

To convert creatinine values from mg/dL to µmol/L, multiply by 88.4.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Spline plots displaying association of creatinine concentration (top), estimated glomerular filtration rate (GFR) (middle), and cystatin C concentration (bottom) with risk for death across the full range in the subcohort of participants without chronic kidney disease.

To convert creatinine values from mg/dL to µmol/L, multiply by 88.4. MDRD = Modification of Diet in Renal Disease.

Grahic Jump Location
Grahic Jump Location
Figure 3.
Cardiovascular events and deaths per 1000 years.
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Summary for Patients

Preclinical Kidney Disease in Elderly People

The summary below is from the full report titled “Cystatin C and Prognosis for Cardiovascular and Kidney Outcomes in Elderly Persons without Chronic Kidney Disease.” It is in the 15 August 2006 issue of Annals of Internal Medicine (volume 145, pages 237-246). The authors are 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, and D.S. Siscovick.

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