Accuracy of GFR Estimating Equations in Patients with Discordances between Creatinine and Cystatin C-Based Estimations

Abstract

Background 

Cystatin C is recommended as a confirmatory test to eGFR when more precise estimates are needed for clinical decision making. Although eGFR on the basis of both creatinine and cystatin (eGFR_cr-cys) is the most accurate estimate in research studies, it is uncertain whether this is true in real-world settings, particularly when there are large discordances between eGFR based on creatinine (eGFR_cr) and that based on cystatin C (eGFR_cys)

Methods 

We included 6185 adults referred for measured GFR (mGFR) using plasma clearance of iohexol in Stockholm, Sweden, who had 9404 concurrent measurements of creatinine, cystatin C, and iohexol clearance. The performance of eGFR_cr, eGFR_cys, and eGFR_cr-cys was assessed against mGFR with median bias, P₃₀, and correct classification of GFR categories. We stratified analyses within three categories: eGFR_cys at least 20% lower than eGFR_cr (eGFR_cys<eGFR_cr), eGFR_cys within 20% of eGFR_cr (eGFR_cys≈eGFR_cr), and eGFR_cys at least 20% higher than eGFR_cr (eGFR_cys>eGFR_cr).

Results 

eGFR_cr and eGFR_cys were similar in 4226 (45%) samples, and among these samples all three estimating equations performed similarly. By contrast, eGFR_cr-cys was much more accurate in cases of discordance. For example, when eGFR_cys<eGFR_cr (47% of samples), the median biases were 15.0 (overestimation), −8.5 (underestimation), and 0.8 ml/min per 1.73 m² for eGFR_cr, eGFR_cys, and eGFR_cr-cys, respectively; P₃₀ was 50%, 73%, and 84%, respectively; and correct classification was 38%, 45%, and 62%, respectively. When eGFR_cys>eGFR_cr (8% of samples), the median biases were −4.5, 8.4, and 1.4 ml/min per 1.73m². The findings were consistent among individuals with cardiovascular disease, heart failure, diabetes mellitus, liver disease, and cancer.

Conclusions 

When eGFR_cr and eGFR_cys are highly discordant in clinical practice, eGFR_cr-cys is more accurate than either eGFR_cr or eGFR_cys.

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