Significance Statement

Large discordances between eGFR on the basis of creatinine (eGFRcr) or cystatin C (eGFRcys) are common in clinical practice. However, which GFR estimating equation (eGFRcr, eGFRcys, or eGFRcr-cys) is most accurate in these settings is not known. In this real-world study of 9404 concurrent measurements of creatinine, cystatin C, and iohexol clearance, all three equations performed similarly when eGFRcr and eGFRcys were similar (45% of cases). However, with large discordances (55% of cases), eGFRcr-cys was much more accurate than either alone. These findings were consistent among individuals with cardiovascular disease, heart failure, diabetes mellitus, liver disease, and cancer who have been underrepresented in research cohorts. Thus, when eGFRcr and eGFRcys are largely discordant in clinical practice, eGFRcr-cys is more accurate than eGFRcr or eGFRcys.

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 (eGFRcr-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 (eGFRcr) and that based on cystatin C (eGFRcys)

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 eGFRcr, eGFRcys, and eGFRcr-cys was assessed against mGFR with median bias, P30, and correct classification of GFR categories. We stratified analyses within three categories: eGFRcys at least 20% lower than eGFRcr (eGFRcyseGFRcr).

Results

eGFRcr and eGFRcys were similar in 4226 (45%) samples, and among these samples all three estimating equations performed similarly. By contrast, eGFRcr-cys was much more accurate in cases of discordance. For example, when eGFRcyseGFRcr (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 eGFRcr and eGFRcys are highly discordant in clinical practice, eGFRcr-cys is more accurate than either eGFRcr or eGFRcys.