Outcomes of KDIGO-Defined CKD in U.S. Veterans With HFpEF, HFmrEF, and HFrEF

Samir Patel¹, Venkatesh K Raman², Charles Faselis³, Gregg C Fonarow⁴, Phillip H Lam⁵, Amiya A Ahmed⁶, Paul A Heidenreich⁷, Stefan D Anker⁸, Prakash Deedwania⁹, Charity J Morgan¹⁰, Sijian Zhang¹, Hans Moore¹¹, Janani Rangaswami¹², George Bakris¹³, Javed Butler¹⁴, Helen M Sheriff¹, Richard M Allman¹⁵, Qing Zeng-Treitler¹, Wen-Chih Wu¹⁶, Ali Ahmed¹⁷

Affiliations

¹ Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Medicine, George Washington University, Washington, District of Columbia, USA.
² Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Medicine, Georgetown University, Washington, District of Columbia, USA.
³ Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Medicine, George Washington University, Washington, District of Columbia, USA; Department of Medicine, Uniformed Services University, Washington, District of Columbia, USA.
⁴ Department of Medicine, University of California, Los Angeles, California, USA. Electronic address: https://twitter.com/gcfmd.
⁵ Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Medicine, Georgetown University, Washington, District of Columbia, USA; Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, District of Columbia, USA. Electronic address: https://twitter.com/PhilLamMD.
⁶ Department of Medicine, Yale University, New Haven, Connecticut, USA.
⁷ Department of Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA; Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
⁸ Department of Cardiology of German Heart Center Charité; German Centre for Cardiovascular Research partner site Berlin, Charité Universitätsmedizin, Berlin, Germany; Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland.
⁹ Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Medicine, University of California, San Francisco, California, USA.
¹⁰ Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
¹¹ Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Medicine, George Washington University, Washington, District of Columbia, USA; Department of Medicine, Georgetown University, Washington, District of Columbia, USA; Department of Medicine, Uniformed Services University, Washington, District of Columbia, USA.
¹² Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Medicine, George Washington University, Washington, District of Columbia, USA. Electronic address: https://twitter.com/RangaswJ.
¹³ Department of Medicine, University of Chicago, Chicago, Illinois, USA.
¹⁴ Baylor Scott and White Research Institute, Dallas, Texas, USA; Department of Medicine, University of Mississippi, Jackson, Mississippi, USA. Electronic address: https://twitter.com/JavedButler1.
¹⁵ Department of Medicine, George Washington University, Washington, District of Columbia, USA; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA.
¹⁶ Department of Medicine, Veterans Affairs Medical Center, Providence, Rhode Island, USA; Department of Medicine, Brown University, Providence, Rhode Island, USA.
¹⁷ Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Medicine, George Washington University, Washington, District of Columbia, USA; Department of Medicine, Georgetown University, Washington, District of Columbia, USA. Electronic address: ali.ahmed@va.gov.

PMID: 39918536
DOI: 10.1016/j.jchf.2024.11.007

Outcomes of KDIGO-Defined CKD in U.S. Veterans With HFpEF, HFmrEF, and HFrEF

Samir Patel et al. JACC Heart Fail. 2025 Mar.

. 2025 Mar;13(3):467-479.

doi: 10.1016/j.jchf.2024.11.007. Epub 2025 Feb 5.

Authors

Affiliations

¹ Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Medicine, George Washington University, Washington, District of Columbia, USA.
² Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Medicine, Georgetown University, Washington, District of Columbia, USA.
³ Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Medicine, George Washington University, Washington, District of Columbia, USA; Department of Medicine, Uniformed Services University, Washington, District of Columbia, USA.
⁴ Department of Medicine, University of California, Los Angeles, California, USA. Electronic address: https://twitter.com/gcfmd.
⁵ Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Medicine, Georgetown University, Washington, District of Columbia, USA; Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, District of Columbia, USA. Electronic address: https://twitter.com/PhilLamMD.
⁶ Department of Medicine, Yale University, New Haven, Connecticut, USA.
⁷ Department of Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA; Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
⁸ Department of Cardiology of German Heart Center Charité; German Centre for Cardiovascular Research partner site Berlin, Charité Universitätsmedizin, Berlin, Germany; Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland.
⁹ Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Medicine, University of California, San Francisco, California, USA.
¹⁰ Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
¹¹ Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Medicine, George Washington University, Washington, District of Columbia, USA; Department of Medicine, Georgetown University, Washington, District of Columbia, USA; Department of Medicine, Uniformed Services University, Washington, District of Columbia, USA.
¹² Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Medicine, George Washington University, Washington, District of Columbia, USA. Electronic address: https://twitter.com/RangaswJ.
¹³ Department of Medicine, University of Chicago, Chicago, Illinois, USA.
¹⁴ Baylor Scott and White Research Institute, Dallas, Texas, USA; Department of Medicine, University of Mississippi, Jackson, Mississippi, USA. Electronic address: https://twitter.com/JavedButler1.
¹⁵ Department of Medicine, George Washington University, Washington, District of Columbia, USA; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA.
¹⁶ Department of Medicine, Veterans Affairs Medical Center, Providence, Rhode Island, USA; Department of Medicine, Brown University, Providence, Rhode Island, USA.
¹⁷ Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia, USA; Department of Medicine, George Washington University, Washington, District of Columbia, USA; Department of Medicine, Georgetown University, Washington, District of Columbia, USA. Electronic address: ali.ahmed@va.gov.

PMID: 39918536
DOI: 10.1016/j.jchf.2024.11.007

Abstract

Background: Chronic kidney disease (CKD) is defined by the KDIGO (Kidney Disease: Improving Global Outcomes) guideline as abnormal kidney structure or function, present for >3 months, with implications for health. KDIGO-defined CKD is associated with poor outcomes in patients with heart failure (HF). Less is known about whether these associations vary by left ventricular ejection fraction.

Objectives: This study aims to determine the prevalence and outcomes of KDIGO-defined CKD in heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), and heart failure with reduced ejection fraction (HFrEF).

Methods: Of the 1,446,053 veterans with an HF diagnosis (1991-2017) in the national Veterans Affairs electronic health record data, 365,000 with data on EF had KDIGO-defined CKD or normal kidney function (NKF). CKD was defined as 2 values measured 90 days apart of estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² (categorized into 4 eGFR stages based on the last eGFR: 45-59 mL/min/1.73 m², 30-44 mL/min/1.73 m², 15-29 mL/min/1.73 m², and <15 mL/min/1.73 m²) or urinary albumin-to-creatinine ratio (uACR) >30 mg/g (albuminuria). NKF was defined as 2 values measured >90 days apart of eGFR ≥60 mL/min/1.73 m², without eGFR <60 mL/min/1.73 m² or albuminuria for 3 years before HF diagnosis. Patients were categorized into HFpEF (EF ≥50%, n = 85,855), HFmrEF (EF 41%-49%, n = 39,397), and HFrEF (EF ≤40%, n = 139,748). HRs and 95% CIs for 5-year all-cause mortality and HF hospitalization through December 31, 2022, associated with the 5 CKD groups (vs NKF) were estimated using Cox regression.

Results: Among patients with HF and NKF, mortality occurred in 39%, 37%. and 41%, and HF hospitalization occurred in 12%, 15%, and 21% of those with HFpEF, HFmrEF. and HFrEF, respectively. Compared with NKF, CKD was associated with 16%, 19%, and 26% higher multivariable-adjusted risks for death in patients with HFpEF, HFmrEF, and HFrEF, respectively. Respective risks for HF hospitalization were 31%, 33%, and 32% higher. The eGFR-associated risks were incrementally higher with decreasing eGFR, except for eGFR <15 mL/min/1.73 m², likely because of the initiation of dialysis during follow-up. Albuminuria was associated with 16%, 10%, and 12% higher multivariable-adjusted risks for death and 29, 30%, and 24% for HF hospitalization in HFpEF, HFmrEF, and HFrEF, respectively. All associations were statistically significant.

Conclusions: These findings based on KDIGO-defined CKD and NKF provide new information about the best estimates of true prevalence and outcomes of CKD in HFpEF, HFmrEF, and HFrEF.

Keywords: KDIGO (Kidney Disease: Improving Global Outcomes); chronic kidney disease; ejection fraction; heart failure; outcomes.

Published by Elsevier Inc.

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Conflict of interest statement

Funding Support and Author Disclosures This work was supported by a grant from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service (I01HX002422) to the Washington DC VA Medical Center. Support for CMS and USRDS Data provided by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service, VA Information Resource Center (Project Numbers SDR 02-237 and 98-004). The funding organization or sponsor played no role in the design, analysis, or interpretation of the current study or in the preparation, review, approval, or the decision to submit the manuscript for publication. The views expressed in this paper are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. Dr Fonarow has received consulting fees from Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Egnite, Janssen, Medtronic, Merck, Novartis, Pfizer, and Urovant; and has received payment or honoraria for lectures from Novartis. Dr Bakris has received consulting fees from Bayer, Janssen, KBP Biosciences, Ionis, Alnylam, Novo Nordisk, Janssen, and InREGEN. Dr Butler has been a consultant to Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Bearing, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Regeneron, Renibus, Roche, Salamandra, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. Drs Ali Ahmed, Wu, and Zeng-Treitler have received research grant funding from National Institutes of Health, Department of Veterans Affairs, and Department of Defense. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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Outcomes of KDIGO-Defined CKD in U.S. Veterans With HFpEF, HFmrEF, and HFrEF

Affiliations

Outcomes of KDIGO-Defined CKD in U.S. Veterans With HFpEF, HFmrEF, and HFrEF

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous