Clinical usefulness of cystatin C for the estimation of glomerular filtration rate in type 1 diabetes: reproducibility and accuracy compared with standard measures and iohexol clearance.

OBJECTIVE-Assessment and follow-up of early renal dysfunction is important in diabetic nephropathy. Plasma creatinine is insensitive for a glomerular filtration rate (GFR) >50 ml/min and creatinine clearance is unwieldy and subject to collection inaccuracies. We aimed to assess the reproducibility, reliability, and accuracy of plasma cystatin C as a measure of GFR ranging from normal to moderate impairment due to type 1 diabetes in the presence of a normal plasma creatinine concentration. RESEARCH DESIGN AND METHODS-A sensitive immunoturbidimetric cystatin C assay was examined in 29 subjects with type 1 diabetes and 11 nondiabetic subjects. Duplicate measurements of the following were collected from each subject, 2 weeks apart: cystatin C, enzymatic plasma creatinine, 24-h creatinine clearance, GFR estimated from plasma creatinine by the Cockcroft-Gault equation, and iohexol clearance as a gold standard. RESULTS-Iohexol clearance ranged from 35 to 132 ml. min(-1). 1.73 m(-2). Plasma cystatin C compared well with the other clinically used tests. The reliability of cystatin C, as assessed by the discriminant ratio, was superior to creatinine clearance (3.4 vs. 1.5, P < 0.001) and the correlation of cystatin C with iohexol clearance (Rs -0.80) was similar to that of creatinine clearance (Rs -0.74) and superior to that of plasma creatinine and the Cockcroft-Gault estimate (Rs -0.54 and 0.66, respectively). Duplicate estimations were used to provide an unbiased equation to convert plasma cystatin C to GFR. CONCLUSIONS-Based on this study, cystatin C is a more reliable measure of GFR than creatinine clearance, is more highly correlated with iohexol clearance than plasma creatinine, and is worthy of further investigation as a clinical measure of GFR in type 1 diabetes.

[1]  Y. Berland,et al.  Cystatin C is not more sensitive than creatinine for detecting early renal impairment in patients with diabetes. , 2001, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[2]  J. McGuire,et al.  Improved immunoturbidimetric assay for cystatin C , 2001, Annals of clinical biochemistry.

[3]  H. Danielsen,et al.  Serum cystatin C as an endogenous parameter of the renal function in patients with normal to moderately impaired kidney function. , 2000, Clinical nephrology.

[4]  J. Kos,et al.  Twenty-four hour variations of cystatin C and total cysteine proteinase inhibitory activity in sera from healthy subjects. , 2000, Clinica chimica acta; international journal of clinical chemistry.

[5]  C. Price,et al.  Adult reference ranges for serum cystatin C, creatinine and predicted creatinine clearance , 2000, Annals of clinical biochemistry.

[6]  P. Nilsson-ehle,et al.  Relationships among serum cystatin C, serum creatinine, lean tissue mass and glomerular filtration rate in healthy adults. , 1999, Scandinavian journal of clinical and laboratory investigation.

[7]  T. Lehtimäki,et al.  Evaluation of plasma cystatin C as a marker for glomerular filtration rate in patients with type 2 diabetes. , 1999, Clinical nephrology.

[8]  E. Erlandsen,et al.  Serum Cystatin C as an Endogenous Marker of the Renal Function – a Review , 1999, Clinical chemistry and laboratory medicine.

[9]  R. Morris,et al.  Discrimination, adjusted correlation, and equivalence of imprecise tests: application to glucose tolerance. , 1999, The American journal of physiology.

[10]  H. Danielsen,et al.  Serum cystatin C as a marker of the renal function. , 1998, Scandinavian journal of clinical and laboratory investigation.

[11]  K. Hruska,et al.  Correlation of plasma concentrations of cystatin C and creatinine to inulin clearance in a pediatric population. , 1998, Clinical chemistry.

[12]  K. Tabei,et al.  Cystatin C measurement and its practical use in patients with various renal diseases. , 1997, Clinical nephrology.

[13]  S. Swan,et al.  The search continues--an ideal marker of GFR. , 1997, Clinical chemistry.

[14]  C. Price,et al.  Serum cystatin C: a replacement for creatinine as a biochemical marker of GFR. , 1994, Kidney international. Supplement.

[15]  P. Nilsson-ehle,et al.  Serum cystatin C, determined by a rapid, automated particle-enhanced turbidimetric method, is a better marker than serum creatinine for glomerular filtration rate. , 1994, Clinical chemistry.

[16]  D B Allison,et al.  Limitations of coefficient of variation as index of measurement reliability. , 1993, Nutrition.

[17]  N. Madias,et al.  Serum creatinine as an index of renal function: new insights into old concepts. , 1992, Clinical chemistry.

[18]  P. O’Reilly,et al.  Iohexol clearance for the determination of glomerular filtration rate in clinical practice: evidence for a new gold standard. , 1991, The Journal of urology.

[19]  Douglas G. Altman,et al.  Practical statistics for medical research , 1990 .

[20]  I. Olafsson,et al.  Structure and expression of the human cystatin C gene. , 1990, The Biochemical journal.

[21]  D. Altman,et al.  STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT , 1986, The Lancet.

[22]  K. Spencer Analytical Reviews in Clinical Biochemistry: The Estimation of Creatinine , 1986, Annals of clinical biochemistry.

[23]  H. Thysell,et al.  The blood serum concentration of cystatin C (gamma-trace) as a measure of the glomerular filtration rate. , 1985, Scandinavian journal of clinical and laboratory investigation.

[24]  P. Nilsson-ehle,et al.  Plasma clearance of a new contrast agent, iohexol: a method for the assessment of glomerular filtration rate. , 1984, The Journal of laboratory and clinical medicine.

[25]  A. Grubb,et al.  Human gamma-trace, a basic microprotein: amino acid sequence and presence in the adenohypophysis. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[26]  A. Grubb,et al.  Quantitation of gamma-trace in human biological fluids: indications for production in the central nervous system. , 1979, Scandinavian journal of clinical and laboratory investigation.

[27]  A. Beckett,et al.  AKUFO AND IBARAPA. , 1965, Lancet.

[28]  Akihiko Hirata,et al.  [Cystatin C]. , 2002, Nihon rinsho. Japanese journal of clinical medicine.

[29]  M. Jung,et al.  Cystatin C: a promising marker of glomerular filtration rate to replace creatinine. , 1995, Nephron.

[30]  L. Prencipe,et al.  A step forward in enzymatic measurement of creatinine. , 1994, Clinical chemistry.

[31]  J. Mandel Fitting Straight Lines When Both Variables are Subject to Error , 1984 .

[32]  B. Brenner,et al.  The role of glomerular hyperfiltration in the initiation and progression of diabetic nephropathy. , 1981, Acta endocrinologica. Supplementum.

[33]  Cockcroft Dw,et al.  Prediction of Creatinine Clearance from Serum Creatinine , 1976 .