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Association of Cystatin C- and Creatinine-Based Estimated Glomerular Filtration Rate With Adverse Outcomes in Heart
Bethany Roehm1, Xiaoyue Zhang2, Jie Yang3
1Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX.
Insights
In heart failure with preserved ejection fraction (HFpEF), a decline in estimated glomerular filtration rate (eGFR) over 12 months predicts adverse cardiovascular outcomes. Cystatin C-based eGFR did not show greater prognostic value than creatinine-based measures in HFpEF.
Area of Science:
- Cardiology
- Nephrology
- Biomarkers
Background:
- Estimated glomerular filtration rate (eGFR) measures, including creatinine-based (eGFRcr) and cystatin C-based (eGFRcys), are crucial for assessing kidney function.
- Previous studies indicate cystatin C-based eGFR is more predictive of adverse outcomes in heart failure with reduced ejection fraction (HFrEF).
- The prognostic value of different eGFR measures in heart failure with preserved ejection fraction (HFpEF) remains less understood.
Purpose of the Study:
- To investigate whether cystatin C-based eGFR measures offer more accurate prognoses than creatinine-based measures in patients with HFpEF.
- To evaluate the association of baseline and changes in eGFR with cardiovascular outcomes in HFpEF.
Main Methods:
- A longitudinal analysis of 214 participants with HFpEF from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial.
- Evaluated baseline, time-varying, and 12-month changes in eGFRcr, eGFRcys, and combined eGFRcr-cys.
- Used Fine-Gray and joint models to assess the composite endpoint of aborted cardiac arrest, heart failure hospitalization, or cardiovascular death.
Main Results:
- All three baseline eGFR measures were independently associated with the composite endpoint after basic adjustments.
- After further adjustment for NT-proBNP and age, no baseline eGFR measure remained statistically significant.
- A relative decline in eGFRcr-cys from baseline to 12 months was significantly associated with the composite endpoint (HR 1.31; 95% CI 1.02-1.67 per 10% decrease).
Conclusions:
- A decline in eGFRcr-cys over 12 months is associated with adverse cardiovascular outcomes in patients with HFpEF.
- Cystatin C-based eGFR measures may not offer superior prognostic value compared to creatinine-based measures in HFpEF.
- Lower eGFR at any timepoint was associated with the composite endpoint in fully adjusted models.
Rationale And Objective:
Cystatin C-based versus creatinine-based measures of estimated glomerular filtration rate (eGFR) are more predictive of worse outcomes in people with heart failure with reduced ejection fraction (HFrEF). It is unknown if cystatin C-based measures may also yield more accurate prognoses in heart failure with preserved ejection fraction (HFpEF).
Study Design:
A longitudinal analysis of people with HFpEF.
Setting & Participants:
214 participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial with available serum at baseline and 12 months in the National Heart, Lung, and Blood Institute's Biologic Specimen and Data Repository Information Coordinating Center.
Exposures:
Baseline, time-varying, or change over 12 months in eGFRcr, eGFRcys, and eGFRcr-cys.
Outcomes:
Composite of aborted cardiac arrest, heart failure hospitalization, or cardiovascular death.
Analytical Approach:
Fine-Gray and joint models.
Results:
Median follow-up was (IQR) 3.09 (2.07-4.44) years. All 3 baseline eGFR measures were independently associated with the risk of the composite endpoint, after adjustment for race, diabetes mellitus, and body mass index: HR (95% CI) per 5mL/min/1.73m2 lower eGFR: eGFRcr, 1.16 (1.04-1.28); eGFRcys, 1.20 (1.08-1.34); eGFRcr-cys, 1.19 (1.08-1.32). After adjusting for NT-proBNP and age, no baseline eGFR measure was statistically significantly associated with the composite endpoint. Only a relative decline in eGFRcr-cys from baseline to 12 months was associated with the composite endpoint in fully adjusted models: eGFRcr-cys, HR 1.31 (1.02-1.67); per 10% eGFR decrease). Lower eGFR at any timepoint, using all 3 measures, was associated with the composite endpoint in fully-adjusted models.
Limitations:
small number of events, possible survival bias.
Conclusions:
A decline in eGFRcr-cys from baseline to 12 months is associated with adverse cardiovascular outcomes in people wit reduced ejection fraction h HFrEF. Measures of eGFR that incorporate only cystatin C may not be of greater prognostic value in people with HFpEF than measures that also incorporate serum creatinine.
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