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The Association of Cystatin C-based eGFR with Functional Exercise Capacity and Patient-Reported Outcomes in Heart
American Journal of Nephrology
|August 11, 2026
Summary
Lower estimated glomerular filtration rate (eGFR) measured by cystatin C, not creatinine, predicts worse outcomes in heart failure (HF) patients. Cystatin C-based eGFR is crucial for assessing functional capacity and quality of life in HF.
Area of Science:
- Nephrology
- Cardiology
- Clinical Trials
Background:
- Lower estimated glomerular filtration rate (eGFR) is linked to adverse outcomes in heart failure (HF) patients with reduced (HFrEF) and preserved (HFpEF) ejection fractions.
- Existing data on the association between eGFR and functional/patient-reported outcomes in HF are inconsistent, particularly for cystatin C-based eGFR (eGFRcys).
Purpose of the Study:
- To evaluate the association between various eGFR measures (creatinine-based, cystatin C-based, and combined) and functional exercise capacity and patient-reported outcomes in HF patients.
- To determine if cystatin C-based eGFR offers superior prognostic value compared to creatinine-based eGFR in HF.
Main Methods:
- Analysis of 769 participants from the EXACT-HF, RELAX, and FIGHT trials, assessing baseline eGFR (eGFRcr, eGFRcys, eGFRcr-cys, and eGFR discordance) against 6-minute walk test (6MWT), Kansas City Cardiomyopathy Questionnaire (KCCQ), and Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores.
- Multivariable linear regression models were employed, adjusting for key clinical variables including age, sex, diabetes, BMI, NYHA class, NT-proBNP, and treatment arm.
Main Results:
- Lower eGFR across all measures correlated with baseline 6MWT performance.
- Cystatin C-derived eGFR measures (eGFRcys, eGFRcr-cys) were significantly associated with 6MWT performance at 6 months, unlike eGFRcr.
- eGFR discordance (eGFRcys/eGFRcr <0.7) predicted a significant drop in 6MWT distance at 6 months.
- Cystatin C-based eGFR measures were also associated with KCCQ scores at 6 months, and eGFRcys/eGFRcr with MLHFQ score improvements.
Conclusions:
- Cystatin C-based eGFR, but not creatinine-based eGFR, effectively predicts poorer functional exercise capacity and patient-reported outcomes at 6 months in individuals with HF.
- These findings underscore the prognostic significance of cystatin C-derived eGFR in managing heart failure patients.
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