Cystatin C Versus Creatinine in Determining Risk Based on Kidney Function

Study Questions:

What is the effect of adding the measurement of cystatin C to that of serum creatinine to determine the estimated glomerular filtration rate (eGFR) on detection, staging, and risk classification of chronic kidney disease across diverse populations?

Methods:

The investigators performed a meta-analysis of 11 general-population studies (with 90,750 participants) and 5 studies of cohorts with chronic kidney disease (2,960 participants) for whom standardized measurements of serum creatinine and cystatin C were available. They 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 (3,471 in 12 cohorts), and end-stage renal disease (1,654 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 <60 ml/min/1.73 m2 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], 0.18-0.28) for death and 0.10 (95% CI, 0.00-0.21) 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 authors concluded that 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.

Perspective:

This study reported that the use of cystatin C improves the role of eGFR in risk categorization, as judged by the risk of death from any cause and to a lesser extent the risks of death from cardiovascular causes and end-stage renal disease. Furthermore, reduced values for cystatin C–based eGFR and eGFR based on combined measurements of creatinine and cystatin C had a consistent linear association with increased risks of death from any cause and from cardiovascular causes for all eGFR levels below approximately 85 ml/min/1.73 m2, which is well above the threshold of 60 ml/min/1.73 m2 for the detection of chronic kidney disease with a creatinine-based eGFR. This suggests that eGFR equations that are based on the measurement of cystatin C can be used to detect increased risks of adverse outcomes that are not detected with creatinine-based calculation of the eGFR.

Keywords: Renal Insufficiency, Kidney Function Tests, Biological Markers, Risk Reduction Behavior, Cardiology, Glomerular Filtration Rate, Creatinine, Cystatin C


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