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

Significance StatementLarge discordances between eGFR on the basis of creatinine (eGFR_cr) or cystatin C (eGFR_cys) are common in clinical practice. However, which GFR estimating equation (eGFR_cr, eGFR_cys, or eGFR_cr-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 eGFR_crand eGFR_cyswere similar (45% of cases). However, with large discordances (55% of cases), eGFR_cr-cyswas 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 eGFR_crand eGFR_cysare largely discordant in clinical practice, eGFR_cr-cysis more accurate than eGFR_cror eGFR_cys.BackgroundCystatin 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)MethodsWe 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-cyswas assessed against mGFR with median bias, P₃₀, and correct classification of GFR categories. We stratified analyses within three categories: eGFR_cysat least 20% lower than eGFR_cr(eGFR_cys<eGFR_cr), eGFR_cyswithin 20% of eGFR_cr(eGFR_cys≈eGFR_cr), and eGFR_cysat least 20% higher than eGFR_cr(eGFR_cys>eGFR_cr).ResultseGFR_crand eGFR_cyswere similar in 4226 (45%) samples, and among these samples all three estimating equations performed similarly. By contrast, eGFR_cr-cyswas 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 m²for eGFR_cr, eGFR_cys, and eGFR_cr-cys, respectively; P₃₀was 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.ConclusionsWhen