Association of Intra-individual Differences in Estimated GFR by Creatinine Versus Cystatin C With Incident Heart Failure

Lower estimated glomerular filtration rate (eGFR) is associated with heart failure (HF) risk. However, eGFR based on cystatin C (eGFR ) and creatinine (eGFR ) may differ substantially within an individual. The clinical implications of these differences for risk of HF among persons with chronic kidne...

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Published in:	American journal of kidney diseases Vol. 80; no. 6; p. 762
Main Authors:	Chen, Debbie C, Shlipak, Michael G, Scherzer, Rebecca, Bansal, Nisha, Potok, O Alison, Rifkin, Dena E, Ix, Joachim H, Muiru, Anthony N, Hsu, Chi-Yuan, Estrella, Michelle M
Format:	Journal Article
Language:	English
Published:	United States 01.12.2022
Subjects:	Adult Creatinine Cystatin C Glomerular Filtration Rate Heart Failure - epidemiology Humans Individuality Prospective Studies Renal Insufficiency, Chronic - epidemiology filtration marker cystatin C eGFR slope Biomarker cardiovascular risk stratification creatinine heart failure (HF) kidney function estimated glomerular filtration rate (eGFR) HF hospitalization chronic kidney disease (CKD) measurement accuracy
ISSN:	1523-6838, 1523-6838
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Abstract	Lower estimated glomerular filtration rate (eGFR) is associated with heart failure (HF) risk. However, eGFR based on cystatin C (eGFR ) and creatinine (eGFR ) may differ substantially within an individual. The clinical implications of these differences for risk of HF among persons with chronic kidney disease (CKD) are unknown. Prospective cohort study. 4,512 adults with CKD and without prevalent HF who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Difference in GFR estimates (eGFR ; ie, eGFR minus eGFR ). Incident HF hospitalization. Fine-Gray proportional subhazards regression was used to investigate the associations of baseline, time-updated, and slope of eGFR with incident HF. Of 4,512 participants, one-third had eGFR and eGFR values that differed by over 15 mL/min/1.73 m . In multivariable-adjusted models, each 15 mL/min/1.73 m lower baseline eGFR was associated with higher risk of incident HF hospitalization (hazard ratio [HR], 1.20 [95% CI, 1.07-1.34]). In time-updated analyses, those with eGFR less than -15 mL/min/1.73 m had higher risk of incident HF hospitalization (HR, 1.99 [95% CI, 1.39-2.86]), and those with eGFR ≥15 mL/min/1.73 m had lower risk of incident HF hospitalization (HR, 0.67 [95% CI, 0.49-0.91]) compared with participants with similar eGFR and eGFR . Participants with faster declines in eGFR relative to eGFR had higher risk of incident HF (HR, 1.49 [95% CI, 1.19-1.85]) compared with those in whom eGFR and eGFR declined in parallel. Entry into the CRIC Study was determined by eGFR , which constrained the range of baseline eGFR -but not eGFR -values. Among persons with CKD who have large differences between eGFR and eGFR , risk for incident HF is more strongly associated with eGFR . Diverging slopes between eGFR and eGFR over time are also independently associated with risk of incident HF.
AbstractList	Lower estimated glomerular filtration rate (eGFR) is associated with heart failure (HF) risk. However, eGFR based on cystatin C (eGFRcys) and creatinine (eGFRcr) may differ substantially within an individual. The clinical implications of these differences for risk of HF among persons with chronic kidney disease (CKD) are unknown.RATIONALE & OBJECTIVELower estimated glomerular filtration rate (eGFR) is associated with heart failure (HF) risk. However, eGFR based on cystatin C (eGFRcys) and creatinine (eGFRcr) may differ substantially within an individual. The clinical implications of these differences for risk of HF among persons with chronic kidney disease (CKD) are unknown.Prospective cohort study.STUDY DESIGNProspective cohort study.4,512 adults with CKD and without prevalent HF who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study.SETTING & PARTICIPANTS4,512 adults with CKD and without prevalent HF who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study.Difference in GFR estimates (eGFRdiff; ie, eGFRcys minus eGFRcr).EXPOSUREDifference in GFR estimates (eGFRdiff; ie, eGFRcys minus eGFRcr).Incident HF hospitalization.OUTCOMEIncident HF hospitalization.Fine-Gray proportional subhazards regression was used to investigate the associations of baseline, time-updated, and slope of eGFRdiff with incident HF.ANALYTICAL APPROACHFine-Gray proportional subhazards regression was used to investigate the associations of baseline, time-updated, and slope of eGFRdiff with incident HF.Of 4,512 participants, one-third had eGFRcys and eGFRcr values that differed by over 15 mL/min/1.73 m2. In multivariable-adjusted models, each 15 mL/min/1.73 m2 lower baseline eGFRdiff was associated with higher risk of incident HF hospitalization (hazard ratio [HR], 1.20 [95% CI, 1.07-1.34]). In time-updated analyses, those with eGFRdiff less than -15 mL/min/1.73 m2 had higher risk of incident HF hospitalization (HR, 1.99 [95% CI, 1.39-2.86]), and those with eGFRdiff ≥15 mL/min/1.73 m2 had lower risk of incident HF hospitalization (HR, 0.67 [95% CI, 0.49-0.91]) compared with participants with similar eGFRcys and eGFRcr. Participants with faster declines in eGFRcys relative to eGFRcr had higher risk of incident HF (HR, 1.49 [95% CI, 1.19-1.85]) compared with those in whom eGFRcys and eGFRcr declined in parallel.RESULTSOf 4,512 participants, one-third had eGFRcys and eGFRcr values that differed by over 15 mL/min/1.73 m2. In multivariable-adjusted models, each 15 mL/min/1.73 m2 lower baseline eGFRdiff was associated with higher risk of incident HF hospitalization (hazard ratio [HR], 1.20 [95% CI, 1.07-1.34]). In time-updated analyses, those with eGFRdiff less than -15 mL/min/1.73 m2 had higher risk of incident HF hospitalization (HR, 1.99 [95% CI, 1.39-2.86]), and those with eGFRdiff ≥15 mL/min/1.73 m2 had lower risk of incident HF hospitalization (HR, 0.67 [95% CI, 0.49-0.91]) compared with participants with similar eGFRcys and eGFRcr. Participants with faster declines in eGFRcys relative to eGFRcr had higher risk of incident HF (HR, 1.49 [95% CI, 1.19-1.85]) compared with those in whom eGFRcys and eGFRcr declined in parallel.Entry into the CRIC Study was determined by eGFRcr, which constrained the range of baseline eGFRcr-but not eGFRcys-values.LIMITATIONSEntry into the CRIC Study was determined by eGFRcr, which constrained the range of baseline eGFRcr-but not eGFRcys-values.Among persons with CKD who have large differences between eGFRcys and eGFRcr, risk for incident HF is more strongly associated with eGFRcys. Diverging slopes between eGFRcys and eGFRcr over time are also independently associated with risk of incident HF.CONCLUSIONSAmong persons with CKD who have large differences between eGFRcys and eGFRcr, risk for incident HF is more strongly associated with eGFRcys. Diverging slopes between eGFRcys and eGFRcr over time are also independently associated with risk of incident HF. Lower estimated glomerular filtration rate (eGFR) is associated with heart failure (HF) risk. However, eGFR based on cystatin C (eGFR ) and creatinine (eGFR ) may differ substantially within an individual. The clinical implications of these differences for risk of HF among persons with chronic kidney disease (CKD) are unknown. Prospective cohort study. 4,512 adults with CKD and without prevalent HF who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Difference in GFR estimates (eGFR ; ie, eGFR minus eGFR ). Incident HF hospitalization. Fine-Gray proportional subhazards regression was used to investigate the associations of baseline, time-updated, and slope of eGFR with incident HF. Of 4,512 participants, one-third had eGFR and eGFR values that differed by over 15 mL/min/1.73 m . In multivariable-adjusted models, each 15 mL/min/1.73 m lower baseline eGFR was associated with higher risk of incident HF hospitalization (hazard ratio [HR], 1.20 [95% CI, 1.07-1.34]). In time-updated analyses, those with eGFR less than -15 mL/min/1.73 m had higher risk of incident HF hospitalization (HR, 1.99 [95% CI, 1.39-2.86]), and those with eGFR ≥15 mL/min/1.73 m had lower risk of incident HF hospitalization (HR, 0.67 [95% CI, 0.49-0.91]) compared with participants with similar eGFR and eGFR . Participants with faster declines in eGFR relative to eGFR had higher risk of incident HF (HR, 1.49 [95% CI, 1.19-1.85]) compared with those in whom eGFR and eGFR declined in parallel. Entry into the CRIC Study was determined by eGFR , which constrained the range of baseline eGFR -but not eGFR -values. Among persons with CKD who have large differences between eGFR and eGFR , risk for incident HF is more strongly associated with eGFR . Diverging slopes between eGFR and eGFR over time are also independently associated with risk of incident HF.
Author	Scherzer, Rebecca Hsu, Chi-Yuan Chen, Debbie C Estrella, Michelle M Ix, Joachim H Shlipak, Michael G Rifkin, Dena E Potok, O Alison Bansal, Nisha Muiru, Anthony N
Author_xml	– sequence: 1 givenname: Debbie C surname: Chen fullname: Chen, Debbie C organization: Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California; Kidney Health Research Collaborative with University of California, San Francisco VA Medical Center, San Francisco, California – sequence: 2 givenname: Michael G surname: Shlipak fullname: Shlipak, Michael G organization: Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California; Kidney Health Research Collaborative with University of California, San Francisco VA Medical Center, San Francisco, California; Department of Medicine, San Francisco VA Medical Center, San Francisco, California – sequence: 3 givenname: Rebecca surname: Scherzer fullname: Scherzer, Rebecca organization: Kidney Health Research Collaborative with University of California, San Francisco VA Medical Center, San Francisco, California; Department of Medicine, San Francisco VA Medical Center, San Francisco, California – sequence: 4 givenname: Nisha surname: Bansal fullname: Bansal, Nisha organization: Kidney Research Institute, Division of Nephrology, School of Medicine, University of Washington, Seattle, Washington; Department of Medicine, School of Medicine, University of Washington, Seattle, Washington – sequence: 5 givenname: O Alison surname: Potok fullname: Potok, O Alison organization: Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, California; Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California – sequence: 6 givenname: Dena E surname: Rifkin fullname: Rifkin, Dena E organization: Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, California; Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California – sequence: 7 givenname: Joachim H surname: Ix fullname: Ix, Joachim H organization: Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, California; Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California – sequence: 8 givenname: Anthony N surname: Muiru fullname: Muiru, Anthony N organization: Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California; Kidney Health Research Collaborative with University of California, San Francisco VA Medical Center, San Francisco, California – sequence: 9 givenname: Chi-Yuan surname: Hsu fullname: Hsu, Chi-Yuan organization: Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California – sequence: 10 givenname: Michelle M surname: Estrella fullname: Estrella, Michelle M email: michelle.estrella@ucsf.edu organization: Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California; Kidney Health Research Collaborative with University of California, San Francisco VA Medical Center, San Francisco, California; Division of Nephrology, San Francisco VA Medical Center, San Francisco, California; Department of Medicine, San Francisco VA Medical Center, San Francisco, California. Electronic address: michelle.estrella@ucsf.edu
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Keywords	filtration marker cystatin C eGFR slope Biomarker cardiovascular risk stratification creatinine heart failure (HF) kidney function estimated glomerular filtration rate (eGFR) HF hospitalization chronic kidney disease (CKD) measurement accuracy
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Snippet	Lower estimated glomerular filtration rate (eGFR) is associated with heart failure (HF) risk. However, eGFR based on cystatin C (eGFR ) and creatinine (eGFR )... Lower estimated glomerular filtration rate (eGFR) is associated with heart failure (HF) risk. However, eGFR based on cystatin C (eGFRcys) and creatinine...
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SubjectTerms	Adult Creatinine Cystatin C Glomerular Filtration Rate Heart Failure - epidemiology Humans Individuality Prospective Studies Renal Insufficiency, Chronic - epidemiology
Title	Association of Intra-individual Differences in Estimated GFR by Creatinine Versus Cystatin C With Incident Heart Failure
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