Estimating GFR Using Serum Cystatin C Alone and in Combination With Serum Creatinine: A Pooled Analysis of 3,418 Individuals With CKD

Lesley A. Stevens, Josef Coresh, Christopher H. Schmid, Harold I. Feldman, Marc Froissart, John Kusek, Jerome Rossert, Frederick Van Lente, Robert D. Bruce, Yaping (Lucy) Zhang, Tom Greene, Andrew S. Levey

Research output: Contribution to journalArticle

Abstract

Background: Serum cystatin C was proposed as a potential replacement for serum creatinine in glomerular filtration rate (GFR) estimation. We report the development and evaluation of GFR-estimating equations using serum cystatin C alone and serum cystatin C, serum creatinine, or both with demographic variables. Study Design: Test of diagnostic accuracy. Setting & Participants: Participants screened for 3 chronic kidney disease (CKD) studies in the United States (n = 2,980) and a clinical population in Paris, France (n = 438). Reference Test: Measured GFR (mGFR). Index Test: Estimated GFR using the 4 new equations based on serum cystatin C alone, serum cystatin C, serum creatinine, or both with age, sex, and race. New equations were developed by using linear regression with log GFR as the outcome in two thirds of data from US studies. Internal validation was performed in the remaining one third of data from US CKD studies; external validation was performed in the Paris study. Measurements: GFR was measured by using urinary clearance of iodine-125-iothalamate in the US studies and chromium-51-EDTA in the Paris study. Serum cystatin C was measured by using Dade-Behring assay, standardized serum creatinine values were used. Results: Mean mGFR, serum creatinine, and serum cystatin C values were 48 mL/min/1.73 m2 (5th to 95th percentile, 15 to 95), 2.1 mg/dL, and 1.8 mg/L, respectively. For the new equations, coefficients for age, sex, and race were significant in the equation with serum cystatin C, but 2- to 4-fold smaller than in the equation with serum creatinine. Measures of performance in new equations were consistent across the development and internal and external validation data sets. Percentages of estimated GFR within 30% of mGFR for equations based on serum cystatin C alone, serum cystatin C, serum creatinine, or both levels with age, sex, and race were 81%, 83%, 85%, and 89%, respectively. The equation using serum cystatin C level alone yields estimates with small biases in age, sex, and race subgroups, which are improved in equations including these variables. Limitations: Study population composed mainly of patients with CKD. Conclusions: Serum cystatin C level alone provides GFR estimates that are nearly as accurate as serum creatinine level adjusted for age, sex, and race, thus providing an alternative GFR estimate that is not linked to muscle mass. An equation including serum cystatin C level in combination with serum creatinine level, age, sex, and race provides the most accurate estimates.

Original languageEnglish (US)
Pages (from-to)395-406
Number of pages12
JournalAmerican Journal of Kidney Diseases
Volume51
Issue number3
DOIs
StatePublished - Mar 2008
Externally publishedYes

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Cystatin C
Glomerular Filtration Rate
Chronic Renal Insufficiency
Creatinine
Serum
Paris
Salivary Cystatins
Iothalamic Acid

Keywords

  • accuracy
  • bias
  • Creatinine
  • cystatin
  • diagnostic tests
  • glomerular filtration rate (GFR)-estimating equations
  • precision

ASJC Scopus subject areas

  • Nephrology

Cite this

Estimating GFR Using Serum Cystatin C Alone and in Combination With Serum Creatinine : A Pooled Analysis of 3,418 Individuals With CKD. / Stevens, Lesley A.; Coresh, Josef; Schmid, Christopher H.; Feldman, Harold I.; Froissart, Marc; Kusek, John; Rossert, Jerome; Van Lente, Frederick; Bruce, Robert D.; Zhang, Yaping (Lucy); Greene, Tom; Levey, Andrew S.

In: American Journal of Kidney Diseases, Vol. 51, No. 3, 03.2008, p. 395-406.

Research output: Contribution to journalArticle

Stevens, LA, Coresh, J, Schmid, CH, Feldman, HI, Froissart, M, Kusek, J, Rossert, J, Van Lente, F, Bruce, RD, Zhang, YL, Greene, T & Levey, AS 2008, 'Estimating GFR Using Serum Cystatin C Alone and in Combination With Serum Creatinine: A Pooled Analysis of 3,418 Individuals With CKD', American Journal of Kidney Diseases, vol. 51, no. 3, pp. 395-406. https://doi.org/10.1053/j.ajkd.2007.11.018
Stevens, Lesley A. ; Coresh, Josef ; Schmid, Christopher H. ; Feldman, Harold I. ; Froissart, Marc ; Kusek, John ; Rossert, Jerome ; Van Lente, Frederick ; Bruce, Robert D. ; Zhang, Yaping (Lucy) ; Greene, Tom ; Levey, Andrew S. / Estimating GFR Using Serum Cystatin C Alone and in Combination With Serum Creatinine : A Pooled Analysis of 3,418 Individuals With CKD. In: American Journal of Kidney Diseases. 2008 ; Vol. 51, No. 3. pp. 395-406.
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abstract = "Background: Serum cystatin C was proposed as a potential replacement for serum creatinine in glomerular filtration rate (GFR) estimation. We report the development and evaluation of GFR-estimating equations using serum cystatin C alone and serum cystatin C, serum creatinine, or both with demographic variables. Study Design: Test of diagnostic accuracy. Setting & Participants: Participants screened for 3 chronic kidney disease (CKD) studies in the United States (n = 2,980) and a clinical population in Paris, France (n = 438). Reference Test: Measured GFR (mGFR). Index Test: Estimated GFR using the 4 new equations based on serum cystatin C alone, serum cystatin C, serum creatinine, or both with age, sex, and race. New equations were developed by using linear regression with log GFR as the outcome in two thirds of data from US studies. Internal validation was performed in the remaining one third of data from US CKD studies; external validation was performed in the Paris study. Measurements: GFR was measured by using urinary clearance of iodine-125-iothalamate in the US studies and chromium-51-EDTA in the Paris study. Serum cystatin C was measured by using Dade-Behring assay, standardized serum creatinine values were used. Results: Mean mGFR, serum creatinine, and serum cystatin C values were 48 mL/min/1.73 m2 (5th to 95th percentile, 15 to 95), 2.1 mg/dL, and 1.8 mg/L, respectively. For the new equations, coefficients for age, sex, and race were significant in the equation with serum cystatin C, but 2- to 4-fold smaller than in the equation with serum creatinine. Measures of performance in new equations were consistent across the development and internal and external validation data sets. Percentages of estimated GFR within 30{\%} of mGFR for equations based on serum cystatin C alone, serum cystatin C, serum creatinine, or both levels with age, sex, and race were 81{\%}, 83{\%}, 85{\%}, and 89{\%}, respectively. The equation using serum cystatin C level alone yields estimates with small biases in age, sex, and race subgroups, which are improved in equations including these variables. Limitations: Study population composed mainly of patients with CKD. Conclusions: Serum cystatin C level alone provides GFR estimates that are nearly as accurate as serum creatinine level adjusted for age, sex, and race, thus providing an alternative GFR estimate that is not linked to muscle mass. An equation including serum cystatin C level in combination with serum creatinine level, age, sex, and race provides the most accurate estimates.",
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T2 - A Pooled Analysis of 3,418 Individuals With CKD

AU - Stevens, Lesley A.

AU - Coresh, Josef

AU - Schmid, Christopher H.

AU - Feldman, Harold I.

AU - Froissart, Marc

AU - Kusek, John

AU - Rossert, Jerome

AU - Van Lente, Frederick

AU - Bruce, Robert D.

AU - Zhang, Yaping (Lucy)

AU - Greene, Tom

AU - Levey, Andrew S.

PY - 2008/3

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N2 - Background: Serum cystatin C was proposed as a potential replacement for serum creatinine in glomerular filtration rate (GFR) estimation. We report the development and evaluation of GFR-estimating equations using serum cystatin C alone and serum cystatin C, serum creatinine, or both with demographic variables. Study Design: Test of diagnostic accuracy. Setting & Participants: Participants screened for 3 chronic kidney disease (CKD) studies in the United States (n = 2,980) and a clinical population in Paris, France (n = 438). Reference Test: Measured GFR (mGFR). Index Test: Estimated GFR using the 4 new equations based on serum cystatin C alone, serum cystatin C, serum creatinine, or both with age, sex, and race. New equations were developed by using linear regression with log GFR as the outcome in two thirds of data from US studies. Internal validation was performed in the remaining one third of data from US CKD studies; external validation was performed in the Paris study. Measurements: GFR was measured by using urinary clearance of iodine-125-iothalamate in the US studies and chromium-51-EDTA in the Paris study. Serum cystatin C was measured by using Dade-Behring assay, standardized serum creatinine values were used. Results: Mean mGFR, serum creatinine, and serum cystatin C values were 48 mL/min/1.73 m2 (5th to 95th percentile, 15 to 95), 2.1 mg/dL, and 1.8 mg/L, respectively. For the new equations, coefficients for age, sex, and race were significant in the equation with serum cystatin C, but 2- to 4-fold smaller than in the equation with serum creatinine. Measures of performance in new equations were consistent across the development and internal and external validation data sets. Percentages of estimated GFR within 30% of mGFR for equations based on serum cystatin C alone, serum cystatin C, serum creatinine, or both levels with age, sex, and race were 81%, 83%, 85%, and 89%, respectively. The equation using serum cystatin C level alone yields estimates with small biases in age, sex, and race subgroups, which are improved in equations including these variables. Limitations: Study population composed mainly of patients with CKD. Conclusions: Serum cystatin C level alone provides GFR estimates that are nearly as accurate as serum creatinine level adjusted for age, sex, and race, thus providing an alternative GFR estimate that is not linked to muscle mass. An equation including serum cystatin C level in combination with serum creatinine level, age, sex, and race provides the most accurate estimates.

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KW - accuracy

KW - bias

KW - Creatinine

KW - cystatin

KW - diagnostic tests

KW - glomerular filtration rate (GFR)-estimating equations

KW - precision

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