Association between serum phosphorus and mortality in NHANES 2003–2006: the effect of gender and renal function

Abstract

Background

The impact of high serum phosphorus in the general population is still debated. Studies are heterogeneous, most lack an adjustment for parathyroid hormone, vitamin D and phosphorus intake and the effect might differ by gender and renal function. We investigated the association between serum phosphorus and mortality in American adults.

Methods

We prospectively analyzed 5698 non-pregnant and non-CKD adults from the National Health and Nutrition Examination Survey (NHANES) 2003–2006. Serum phosphorus and potential confounders including parathyroid hormone, 25(OH)vitamin D and phosphorus intake were evaluated. All-cause, cardiovascular- and cancer-related deaths were recorded through December 31st, 2015. Sex-specific terciles of serum phosphorus were used to fit adjusted Cox proportional hazard models for mortality. Analysis was stratified by gender and renal function.

Results

A total of 590 deaths were recorded over a median follow-up of 81 months. Women showed higher serum phosphorus than men. The adjusted hazard ratio (HR) for all-cause mortality was 1.35 (95% CI 1.08–1.58) (p = 0.033) for the third tercile (versus second tercile). This increased risk was present in participants with estimated glomerular filtration rate (eGFR) below 90 ml/min/1.73 m2 but not above, although interaction was not significant (p = 0.12). Interaction by gender, phosphorus intake, PTH and fasting time was also not detected. For cardiovascular and cancer mortality, the adjusted HR was 0.81 (95% CI 0.33–2.00) (p = NS) and 1.45 (95% CI 0.77–2.72) (p = NS), respectively.

Conclusions

We demonstrated that the highest tercile of serum phosphorus is associated with increased all-cause mortality, irrespective of PTH, 25(OH)vitamin D or phosphorus intake. This association may differ by gender and renal function, but larger studies testing for effect modification are needed.

Graphic abstract

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Code and data availability

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

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Acknowledgements

The authors thank the participants and staff of the NHANES. The authors thank João Sérgio Neves, MD, from Serviço de Endocrinologia, Diabetes e Metabolismo, Centro Hospitalar Universitário de São João, Faculdade de Medicina, Universidade do Porto (Porto, Portugal) who provided insight that greatly assisted the statistical analysis.

Funding

This work was supported through the Cardiovascular Research Center (UnIC, FCT 51/94) by the Portuguese Foundation for Science and Technology and by the project NETDIAMOND (POCI-01-0145-FEDER-016385, supported by European Structural and Investment Funds and Lisbon's Regional Operational Program 2020). Funders of this study had no role in the study design; collection, analysis, or interpretation of the data; writing of the report; or the decision to submit this report for publication.

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Contributions

Research idea: LM. Literature search, study design, data analysis and first manuscript draft preparation: LM, FG, LP. Interpretation of the results and critical revision of the manuscript: SS, PCC, LP. 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.

Corresponding author

Correspondence to Luís Mendonça.

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The authors declare that they have no relevant financial interests.

Ethics approval

NHANES protocols were approved by the National Center for Health Statistics Ethics Review Board: NHANES 2003–2004 (Protocol #98-12) and NHANES 2005–2006 (Protocol #2005-06).

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Mendonça, L., Gonçalves, F., Sampaio, S. et al. Association between serum phosphorus and mortality in NHANES 2003–2006: the effect of gender and renal function. J Nephrol (2021). https://doi.org/10.1007/s40620-021-00969-4

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Keywords

  • Phosphorus
  • Parathyroid hormone
  • 25(OH)vitamin D
  • Mortality