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Association of combined fractional excretion of phosphate and FGF23 with heart failure and cardiovascular events in moderate and advanced renal disease

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Abstract

Background

High levels of FGF23 associate with adverse events in CKD. The urinary fractional excretion of phosphate (FePi) might modify this association, although data are limited in moderate and advanced CKD. We investigated the association of combined FePi and serum FGF23 with incident heart failure, cardiovascular events and mortality in patients with CKD stages 2–4.

Methods

Patients from the Chronic Renal Insufficiency Cohort were divided into four groups according to the median of FePi and FGF23: low-FePi/low-FGF23, reference group; high-FePi/low-FGF23; low-FePi/high-FGF23; high-FePi/high-FGF23. Primary outcomes were: the composite of cardiovascular death or hospitalization for heart failure; cardiovascular death; hospitalization for heart failure; and death from any cause. Survival analysis and adjusted regression analyses were performed.

Results

We analyzed 3684 patients with a mean age of 58 ± 11 years of whom 45% were male. Mean eGFR was 44 ± 15 ml/min/1.73 m2. The median time of follow-up was 12 (IQR 7–13) years. The risk of the composite of cardiovascular death or hospitalization for heart failure was increased in the low-FePi/high-FGF23 group (HR 1.35; 95%CI 1.09–1.67) and in the high-FePi/high-FGF23 group (HR 1.50; 95%CI 1.20–1.86), compared to the low-FePi/low-FGF23 group. Cardiovascular death and hospitalization for heart failure were also increased in both groups with high FGF23. Death from any cause was increased in the low-FePi/high-FGF23 group (HR 1.56 (95%CI 1.30–1.89) and in the high-FePi/high-FGF23 (HR 1.57 (95%CI 1.29–1.90)).

Conclusions

High FGF23 was associated with heart failure and cardiovascular death in patients with low FePi and high FePi with moderate to advanced CKD. This contrasts with reports in mild CKD.

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Code and data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by the projects: (i) “New targets in diastolic heart failure: from comorbidities to personalized medicine – NETDIAMOND” co-financed by the European Structural and Investment Funds (ESIF), through the Programa Operacional Regional Lisboa 2020 (POCI-01-0145-FEDER-016385) and national funds by FCT Fundação para a Ciência e Tecnologia, I.P. (SAICT-PAC/0047/2015); and (ii) Cardiovascular R&D Center–UnIC (UIDB/00051/2020 and UIDP/00051/2020), financed by national funds through FCT–Portuguese Foundation for Science and Technology.

Author information

Author notes

  1. Luís Mendonça and Miguel Bigotte Vieira contributed equally to this work.

Authors and Affiliations

  1. Nephrology Department, Centro Hospitalar Universitário de São João, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal

    Luís Mendonça

  2. Department of Surgery and Physiology, Cardiovascular Research and Development Center, Faculty of Medicine, University of Porto, Porto, Portugal

    Luís Mendonça & João Sérgio Neves

  3. Nephrology Department, Hospital Curry Cabral, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal

    Miguel Bigotte Vieira

  4. Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal

    João Sérgio Neves

Authors
  1. Luís Mendonça
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  2. Miguel Bigotte Vieira
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  3. João Sérgio Neves
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Contributions

Research idea: LM. Literature search, study design, data analysis and first manuscript draft preparation: LM, MBV, JSN. Interpretation of the results and critical revision of the manuscript: LM, MBV, JSN. Each author contributed important intellectual content during manuscript drafting or revision, accepts personal accountability for the author’s own contributions, read and approved the final manuscript and agrees to ensure that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. LM, MBV, JSN: Responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

Corresponding author

Correspondence to Luís Mendonça.

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Conflict of interest

The authors report no relationships that could be construed as a conflict of interest.

Ethical approval

The CRIC Study protocol was approved by the institutional review boards of all participating centers: the University of Pennsylvania Institutional Review Board (Federalwide Assurance # 00004028), Johns Hopkins Institutional Review Board (Study # NA_00044034/CIR00004697), The University of Maryland, Baltimore Institutional Review Board, University Hospitals Cleveland Medical Center Institutional Review Board, MetroHealth Institutional Review Board, Cleveland Clinic Foundation Institutional Review Board (IRB #5969), University of Michigan Medical School Institutional Review Board (IRBMED), Wayne State University Institutional Review Board, University of Illinois at Chicago Institutional Review Board, Tulane Human Research Protection Office, Institutional Review Boards, Biomedical Social Behavioral (reference#: 140987), and Kaiser Permanente Northern California Institutional Review Board.

Informed consent

The study is in accordance with the Declaration of Helsinki. All CRIC participants provided written informed consent.

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Mendonça, L., Bigotte Vieira, M. & Neves, J.S. Association of combined fractional excretion of phosphate and FGF23 with heart failure and cardiovascular events in moderate and advanced renal disease. J Nephrol 36, 55–67 (2023). https://doi.org/10.1007/s40620-022-01358-1

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  • DOI: https://doi.org/10.1007/s40620-022-01358-1

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