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

Abstract

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, P 30, and correct classification of GFR categories. We stratified analyses within three categories: eGFRcys at least 20% lower than eGFRcr (eGFRcys<eGFRcr), eGFRcys within 20% of eGFRcr (eGFRcys≈eGFRcr), and eGFRcys at least 20% higher than eGFRcr (eGFRcys>eGFRcr). 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 eGFRcys<eGFRcr (47% of samples), the median biases were 15.0 (overestimation), −8.5 (underestimation), and 0.8 ml/min per 1.73 m2 for eGFRcr, eGFRcys, and eGFRcr-cys, respectively; P 30 was 50%, 73%, and 84%, respectively; and correct classification was 38%, 45%, and 62%, respectively. When eGFRcys>eGFRcr (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.