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The Association of Cystatin C-based eGFR with Functional Exercise Capacity and Patient-Reported Outcomes in Heart

Blake Lackey, Bethany Roehm, Justin L Grodin

    American Journal of Nephrology
    |August 11, 2026
    PubMed

    Insights

    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.
    Abstract

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