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Published ahead of print on March 23, 2005
J Am Soc Nephrol 16: 1404-1412, 2005
© 2005 American Society of Nephrology
doi: 10.1681/ASN.2004100854
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Clinical Nephrology

Detection of Renal Function Decline in Patients with Diabetes and Normal or Elevated GFR by Serial Measurements of Serum Cystatin C Concentration: Results of a 4-Year Follow-Up Study

Bruce A. Perkins*,{dagger}, Robert G. Nelson{ddagger}, Betsy E.P. Ostrander*, Kristina L. Blouch§, Andrzej S. Krolewski*,{dagger}, Bryan D. Myers§ and James H. Warram*

* Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, Massachusetts; {dagger} Department of Medicine, Harvard Medical School, Boston, Massachusetts; {ddagger} Diabetes and Arthritis Epidemiology Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona; and § Division of Nephrology, Stanford University School of Medicine, Stanford, California

Address correspondence to: Dr. James H. Warram, Section on Genetics and Epidemiology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. Phone: 617-732-2668; Fax: 617-732-2667; E-mail: james.warram{at}joslin.harvard.edu

Received for publication October 15, 2004. Accepted for publication February 4, 2005.

Research on early renal function decline in diabetes is hampered by lack of simple tools for detecting trends (particularly systematic decreases) in renal function over time when GFR is normal or elevated. This study sought to assess how well serum cystatin C meets that need. Thirty participants with type 2 diabetes in the Diabetic Renal Disease Study met these three eligibility criteria: GFR >20 ml/min per 1.73 m2 at baseline (based on cold iothalamate clearance), 4 yr of follow-up, and yearly measurements of iothalamate clearance and serum cystatin C. With the use of linear regression, each individual’s trend in renal function over time, expressed as annual percentage change in iothalamate clearance, was determined. Serum cystatin C in mg/L was transformed to its reciprocal (100/cystatin C), and linear regression was used to determine each individual’s trend over time, expressed as annual percentage change. In paired comparisons of 100/cystatin C with iothalamate clearance at each examination, the two measures were numerically similar. More important, the trends in 100/cystatin C and iothalamate clearance were strongly correlated (Spearman r = 0.77). All 20 participants with negative trends in iothalamate clearance (declining renal function) also had negative trends for 100/cystatin C. Results were discordant for only three participants. In contrast, the trends for three commonly used creatinine-based estimates of GFR compared poorly with trends in iothalamate clearance (Spearman r < 0.35). Serial measures of serum cystatin C accurately detect trends in renal function in patients with normal or elevated GFR and provide means for studying early renal function decline in diabetes.




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