Discordance Between Creatinine-Based and Cystatin C-Based Estimated GFR: Interpretation According to Performance Compared to Measured GFR

Yeli Wang; Ogechi M Adingwupu; Michael G Shlipak; Alessandro Doria; Michelle M Estrella; Marc Froissart; Vilmundur Gudnason; Anders Grubb; Roberto Kalil; Michael Mauer; Peter Rossing; Jesse Seegmiller; Josef Coresh; Andrew S Levey; Lesley A Inker

doi:10.1016/j.xkme.2023.100710

Discordance Between Creatinine-Based and Cystatin C-Based Estimated GFR: Interpretation According to Performance Compared to Measured GFR

Kidney Med. 2023 Aug 9;5(10):100710. doi: 10.1016/j.xkme.2023.100710. eCollection 2023 Oct.

Authors

Affiliations

¹ Department of Nutrition, Harvard University T.H. Chan School of Public Health, Boston, MA.
² Division of Nephrology, Tufts Medical Center, Boston, MA.
³ Kidney Health Research Collaborative, San Francisco Veterans Affair Medical Center and University of California, San Francisco, CA.
⁴ Section on Genetics & Epidemiology, Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, MA.
⁵ Division of Nephrology, Department of Medicine, San Francisco VA Health Care System and University of California, San Francisco, CA.
⁶ Clinical Trial Unit, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
⁷ Faculty of Medicine, University of Iceland, Reykjavik, and the Icelandic Heart Association, Kopavogur, Iceland.
⁸ Department of Clinical Chemistry and Pharmacology, Institute of Laboratory Medicine, Lund University, Sweden.
⁹ Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore MD.
¹⁰ Divisions of Pediatric and Adult Nephrology, University of Minnesota, Minneapolis, MN.
¹¹ Steno Diabetes Center Copenhagen and the Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹² Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN.
¹³ Department of Epidemiology, John Hopkins Bloomberg School of Public Health, Baltimore, MD.

Abstract

Rationale & objective: Use of cystatin C in addition to creatinine to estimate glomerular filtration rate (estimated glomerular filtration rate based on cystatin C [eGFRcys] and estimated glomerular filtration rate based on creatinine [eGFRcr], respectively) is increasing. When eGFRcr and eGFRcys are discordant, it is not known which is more accurate, leading to uncertainty in clinical decision making.

Study design: Cross-sectional analysis.

Setting & participants: Four thousand fifty participants with measured glomerular filtration rate (mGFR) from 12 studies in North America and Europe.

Exposures: Serum creatinine and serum cystatin C.

Outcomes: Performance of creatinine-based and cystatin C-based glomerular filtration rate estimating equations compared to mGFR.

Analytical approach: We evaluated the accuracy of eGFRcr, eGFRcys, and the combination (eGFRcr-cys) compared to mGFR according to the magnitude of the difference between eGFRcr and eGFRcys (eGFRdiff). We used CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations to estimate glomerular filtration rate. eGFRdiff was defined as eGFRcys minus eGFRcr and categorized as less than -15, -15 to <15, and ≥15 mL/min/1.73 m² (negative, concordant, and positive groups, respectively). We compared bias (median of mGFR minus eGFR) and the percentage of eGFR within 30% of mGFR.

Results: Thirty percent of participants had discordant eGFRdiff (21.0% and 9.6% negative and positive eGFRdiffs, respectively). In the concordant eGFRdiff group, all equations displayed similar accuracy. In the negative eGFRdiff groups, eGFRcr had a large overestimation of mGFR (-13.4 [-14.5 to -12.2] mL/min/1.73 m²) and eGFRcys had a large underestimation (9.9 [9.1-11.2] mL/min/1.73m²), with opposite results in the positive eGFRdiff group. In both negative and positive eGFRdiff groups, eGFRcr-cys was more accurate than either eGFRcr or eGFRcys. These results were largely consistent across age, sex, race, and body mass index.

Limitations: Few participants with major comorbid conditions.

Conclusions: Discordant eGFRcr and eGFRcys are common. eGFR using the combination of creatinine and cystatin C provides the most accurate estimates among persons with discordant eGFRcr or eGFRcys.

Keywords: Glomerular filtration rate; creatinine; cystatin; estimated GFR.

Grants and funding

P30 DK036836/DK/NIDDK NIH HHS/United States