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 (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 cr and eGFR cys were similar (45% of cases). However, with large discordances (55% of cases), eGFR cr-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 eGFR cr and eGFR cys are largely discordant in clinical practice, eGFR cr-cys is more accurate than eGFR cr or eGFR cys .

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 m 2 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 1.73m 2 . 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 .

Graphical abstract

Figure 1

Density plot of bias for three eGFR equations, overall and stratified by discordance between eGFR_cr and eGFR_cys. A measurement fell within eGFR_cys<eGFR_cr when eGFR_cys was more than 20% lower than eGFR_cr; eGFR_cys≈eGFR_cr if the difference between eGFR values was within 20% of eGFR_cr and within eGFR_cys>eGFR_cr when eGFR_cys was more than 20% higher than eGFR_cr. Figure 1 can be viewed in color online at www.jasn.org.

Figure 2

Bias of eGFR_cr, eGFR_cys, and eGFR_cr-cys across subgroups, overall and stratified by the extent of discordance between eGFR_cr and eGFR_cys. A measurement fell within eGFR_cys<eGFR_cr when eGFR_cys was more than 20% lower than eGFR_cr; eGFR_cys≈eGFR_cr if the difference between eGFR values was within 20% of eGFR_cr and within eGFR_cys>eGFR_cr when eGFR_cys was more than 20% higher than eGFR_cr. BMI, body mass index; CVD, cardiovascular disease; DM, diabetes mellitus; HF, heart failure; mGFR, measured glomerular filtration rate. Figure 2 can be viewed in color online at www.jasn.org.