Introduction: Serum creatinine is the traditional biomarker for estimating glomerular filtration rate (eGFR). Cystatin C is an alternative biomarker for which estimating equations exist. The use of cystatin C testing, and the interrelationships among the recently revised Chronic Kidney Disease Epidemiology (CKD-EPI) 2021 estimating equations, was evaluated in a national outpatient laboratory dataset. Methods: Cystatin C results reported on adults between November 2011 and June 2018 by Laboratory Corporation of America Holdings were examined, with classification of ordering providers and diagnostic codes. Updated eGFR results were calculated using the CKD-EPI 2021 equations for each sample with both cystatin C and creatinine values available. The Spearman correlation coefficients were calculated. Reclassification at clinically relevant cut-off values was examined. Results: There were 87,803 serum cystatin C levels among 55,360 patients; mean age 58 ± 17 years; 50% women. Cystatin C usage increased over time and was ordered for many indications. Among 73,367 samples with simultaneous creatinine and cystatin C, r = 0.84 between eGFR-creatinine and eGFR-cystatin. Correlations of eGFR-creatinine, eGFR-cystatin, and the averaged result of the two equations to the new combined equation were r = 0.94, r = 0.97, and r = 0.998, respectively (p < 0.001 for all). Use of combined/averaged equations tended to result in a higher eGFR and upclassification, compared to eGFR-creatinine. Conclusion/Discussion: Use of Cystatin C is increasing and has moved beyond the nephrology community and the original indications from the 2012 KDIGO guidelines. Community utilization of cystatin C measurement is likely to expand, and understanding of the relationships between estimating equations will help clinicians optimize their use in the outpatient setting.

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