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American Journal of Kidney Diseases

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

  • Debbie C. Chen
    Affiliations
    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
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  • Michael G. Shlipak
    Affiliations
    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
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  • Rebecca Scherzer
    Affiliations
    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
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  • Nisha Bansal
    Affiliations
    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
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  • O. Alison Potok
    Affiliations
    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
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  • Dena E. Rifkin
    Affiliations
    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
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  • Joachim H. Ix
    Affiliations
    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
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  • Anthony N. Muiru
    Affiliations
    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
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  • Chi-yuan Hsu
    Affiliations
    Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California
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  • Michelle M. Estrella
    Correspondence
    Address for Correspondence: Michelle M. Estrella, MD, MHS, 4150 Clement St, Bldg 2, Rm 145, San Francisco, CA 94121.
    Affiliations
    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
    Search for articles by this author

      Rationale & Objective

      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.

      Study Design

      Prospective cohort study.

      Setting & Participants

      4,512 adults with CKD and without prevalent HF who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study.

      Exposure

      Difference in GFR estimates (eGFRdiff; ie, eGFRcys minus eGFRcr).

      Outcome

      Incident HF hospitalization.

      Analytical Approach

      Fine-Gray proportional subhazards regression was used to investigate the associations of baseline, time-updated, and slope of eGFRdiff with incident HF.

      Results

      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.

      Limitations

      Entry into the CRIC Study was determined by eGFRcr, which constrained the range of baseline eGFRcr—but not eGFRcys—values.

      Conclusions

      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.

      Graphical abstract

      Index Words

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