Cystatin C versus Creatinine in Determining Risk Based on Kidney Function

Michael G. Shlipak, Kunihiro Matsushita, Johan Arnlov, Lesley A. Inker, Ronit Katz, Kevan R. Polkinghorne, Dietrich Rothenbacher, Mark J. Sarnak, Brad C. Astor, Josef Coresh*, Andrew S. Levey, Ron T. Gansevoort, CKD Prognosis Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

725 Citations (Scopus)

Abstract

BACKGROUND

Adding the measurement of cystatin C to that of serum creatinine to determine the estimated glomerular filtration rate (eGFR) improves accuracy, but the effect on detection, staging, and risk classification of chronic kidney disease across diverse populations has not been determined.

METHODS

We performed a meta-analysis of 11 general-population studies (with 90,750 participants) and 5 studies of cohorts with chronic kidney disease (2960 participants) for whom standardized measurements of serum creatinine and cystatin C were available. We compared the association of the eGFR, as calculated by the measurement of creatinine or cystatin C alone or in combination with creatinine, with the rates of death (13,202 deaths in 15 cohorts), death from cardiovascular causes (3471 in 12 cohorts), and end-stage renal disease (1654 cases in 7 cohorts) and assessed improvement in reclassification with the use of cystatin C.

RESULTS

In the general-population cohorts, the prevalence of an eGFR of less than 60 ml per minute per 1.73 m(2) of body-surface area was higher with the cystatin C-based eGFR than with the creatinine-based eGFR (13.7% vs. 9.7%). Across all eGFR categories, the reclassification of the eGFR to a higher value with the measurement of cystatin C, as compared with creatinine, was associated with a reduced risk of all three study outcomes, and reclassification to a lower eGFR was associated with an increased risk. The net reclassification improvement with the measurement of cystatin C, as compared with creatinine, was 0.23 (95% confidence interval [CI], 0.18 to 0.28) for death and 0.10 (95% CI, 0.00 to 0.21) for end-stage renal disease. Results were generally similar for the five cohorts with chronic kidney disease and when both creatinine and cystatin C were used to calculate the eGFR.

CONCLUSIONS

The use of cystatin C alone or in combination with creatinine strengthens the association between the eGFR and the risks of death and end-stage renal disease across diverse populations.

Original languageEnglish
Pages (from-to)932-943
Number of pages12
JournalNew England Journal of Medicine
Volume369
Issue number10
DOIs
Publication statusPublished - 5-Sept-2013

Keywords

  • GLOMERULAR-FILTRATION-RATE
  • STAGE RENAL-DISEASE
  • COLLABORATIVE METAANALYSIS
  • POPULATION COHORTS
  • HIGHER ALBUMINURIA
  • ESTIMATED GFR
  • ALL-CAUSE
  • GENERAL-POPULATION
  • HEART-FAILURE
  • CKD-EPI

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