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Updated: Oct 18, 2025
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
The difference between cystatin C- and creatinine-based eGFR is associated with adverse cardiovascular outcome in
Hyoungnae Kim1, Jung Tak Park2, Joongyub Lee3
1Division of Nephrology, Soonchunhyang University Seoul Hospital, Seoul, South Korea.
Insights
A large difference between creatinine- and cystatin C-based estimated kidney function (eGFR) indicates a higher risk of major adverse cardiovascular events (MACE) and faster progression of coronary artery calcification in patients with chronic kidney disease (CKD).
Area of Science:
- Nephrology
- Cardiology
- Biomarkers
Background:
- Decreased kidney function is a significant risk factor for cardiovascular disease (CVD).
- Discrepancies between creatinine-based (eGFRcreat) and cystatin C-based (eGFRcys) estimated glomerular filtration rates (eGFR) complicate CVD risk assessment in chronic kidney disease (CKD) patients.
- The association between the difference in eGFR values (eGFRdiff) and major adverse cardiovascular events (MACE) in CKD requires further investigation.
Purpose of the Study:
- To investigate the association between the difference in eGFRcreat and eGFRcys (eGFRdiff) and the risk of MACE in patients with CKD.
- To explore the relationship between eGFRdiff and coronary artery calcification (CAC) progression in CKD patients.
Main Methods:
- A prospective cohort study involving 2076 CKD patients staged according to KDIGO guidelines.
- eGFRdiff was calculated as eGFRcreat minus eGFRcys.
- MACE was the primary outcome, defined as non-fatal myocardial infarction, unstable angina, stroke, congestive heart failure, symptomatic arrhythmia, or cardiac death. CAC progression was also assessed.
Main Results:
- During a median follow-up of 4.1 years, 147 MACE occurred.
- Patients in the highest tertile of baseline eGFRdiff exhibited a significantly higher risk of MACE (HR, 2.12) compared to the lowest tertile.
- Higher eGFRdiff was associated with increased baseline CAC (OR, 1.38) and accelerated CAC progression (OR, 1.03).
Conclusions:
- A substantial positive difference between eGFRcreat and eGFRcys is linked to an elevated risk of MACE and accelerated CAC progression in CKD patients.
- These findings underscore the importance of considering eGFR discrepancies in cardiovascular risk stratification for CKD patients.
- Close cardiovascular monitoring is recommended for individuals with a larger eGFRdiff.
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.
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