The difference between cystatin C- and creatinine-based eGFR is associated with adverse cardiovascular outcome in patients with chronic kidney disease

Hyoungnae Kim, Jung Tak Park, Joongyub Lee, Ji Yong Jung, Kyu Beck Lee, Yeong Hoon Kim, Tae Hyun Yoo, Shin Wook Kang, Kyu Hun Choi, Kook Hwan Oh, Curie Ahn, Seung Hyeok Han

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5 Citations (Scopus)


Background and aims: Decreased kidney function is an important risk factor for cardiovascular disease (CVD). However, assessing risk of CVD may be difficult when there is a gap between creatinine- and cystatin C-based estimated glomerular filtration rate (eGFR). We studied the association of the difference in eGFRs with major adverse cardiovascular events (MACE) in patients with chronic kidney disease (CKD). Methods: This prospective cohort study was conducted in 2076 patients with CKD stages based on the KDIGO guideline (eGFR categories of G1: ≥90; G 2: 60–89; G3: 30–59; G4: 15–29; G5: <15 mL/min/1.73 m2 without kidney replacement therapy). The difference in eGFR (eGFRdiff) was calculated by subtracting the cystatin C-based eGFR (eGFRcys) from the creatinine-based eGFR (eGFRcreat). The primary outcome was MACE, defined as non-fatal acute myocardial infarction and unstable angina, stroke, congestive heart failure, symptomatic arrhythmia, and cardiac death. Results: During a median follow-up of 4.1 years, MACE occurred in 147 patients (incidence rate, 15.0 per 1000 patient-years). When patients were categorized into baseline eGFRdiff tertiles, the highest tertile was associated with a significantly higher risk of MACE (hazard ratio, 2.12; 95% confidence interval [CI], 1.28–3.51) than the lowest tertile when adjusted for eGFRcreat, eGFRcys, or eGFR based on both creatinine and cystatin C. Patients in the highest tertile had more baseline coronary artery calcification (CAC) than those in the lowest tertile (odds ratio [OR], 1.38; 95% CI, 1.03–1.86). In addition, 978 patients had data for both baseline and follow-up CAC at year 4. In this subgroup, baseline eGFRdiff was significantly associated with accelerated CAC progression (≥50/year) (OR, 1.03; 95% CI, 1.01–1.05). Conclusions: A large positive difference between eGFRcreat and eGFRcys was associated with a higher risk of MACE and faster CAC progression in patients with CKD. Therefore, careful monitoring of CVD is needed for patients with a higher eGFRdiff.

Original languageEnglish
Pages (from-to)53-61
Number of pages9
Publication statusPublished - 2021 Oct

Bibliographical note

Funding Information:
This work was supported by the Research Program funded by the Korea Disease Control and Prevention Agency ( 2011E3300300 , 2012E3301100 , 2013E3301600 , 2013E3301601 , 2013E3301602 , 2016E3300200 , 2016E3300201 , 2016E3300202 , 2019E320100 , 2019E320101 , and 2019E320102 ) and Soonchunhyang University Research Fund. Sponsors were not involved in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Publisher Copyright:
© 2021 Elsevier B.V.

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine


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