Preoperative inflammatory biomarkers reveal renal involvement in postsurgical mortality in hip fracture patients: an exploratory study

Front Immunol. 2024 Jun 10:15:1372079. doi: 10.3389/fimmu.2024.1372079. eCollection 2024.

Abstract

Background: Hip fractures in frail patients result in excess mortality not accounted for by age or comorbidities. The mechanisms behind the high risk of mortality remain undetermined but are hypothesized to be related to the inflammatory status of frail patients.

Methods: In a prospective observational exploratory cohort study of hospitalized frail hip fracture patients, 92 inflammatory markers were tested in pre-operative serum samples and markers were tested against 6-month survival post-hip fracture surgery and incidence of acute kidney injury (AKI). After correcting for multiple testing, adjustments for comorbidities and demographics were performed on the statistically significant markers.

Results: Of the 92 markers tested, circulating levels of fibroblast growth factor 23 (FGF-23) and interleukin-15 receptor alpha (IL15RA), both involved in renal disease, were significantly correlated with 6-month mortality (27.5% overall) after correcting for multiple testing. The incidence of postoperative AKI (25.4%) was strongly associated with 6-month mortality, odds ratio = 10.57; 95% CI [2.76-40.51], and with both markers plus estimated glomerular filtration rate (eGFR)- cystatin C (CYSC) but not eGFR-CRE. The effect of these markers on mortality was significantly mediated by their effect on postoperative AKI.

Conclusion: High postoperative mortality in frail hip fracture patients is highly correlated with preoperative biomarkers of renal function in this pilot study. The effect of preoperative circulating levels of FGF-23, IL15RA, and eGFR-CYSC on 6-month mortality is in part mediated by their effect on postoperative AKI. Creatinine-derived preoperative renal function measures were very poorly correlated with postoperative outcomes in this group.

Keywords: FGF23; acute kidney injury; frailty; hip fracture; inflammation; mortality; renal; surgery.

Publication types

  • Observational Study

MeSH terms

  • Acute Kidney Injury* / blood
  • Acute Kidney Injury* / diagnosis
  • Acute Kidney Injury* / etiology
  • Acute Kidney Injury* / mortality
  • Aged
  • Aged, 80 and over
  • Biomarkers* / blood
  • Female
  • Fibroblast Growth Factor-23*
  • Fibroblast Growth Factors / blood
  • Glomerular Filtration Rate
  • Hip Fractures* / blood
  • Hip Fractures* / mortality
  • Hip Fractures* / surgery
  • Humans
  • Inflammation / blood
  • Male
  • Postoperative Complications / blood
  • Postoperative Complications / etiology
  • Postoperative Complications / mortality
  • Preoperative Period
  • Prospective Studies

Substances

  • Biomarkers
  • Fibroblast Growth Factor-23
  • FGF23 protein, human
  • Fibroblast Growth Factors

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Institute for Health and Care Research (NIHR) Nottingham Biomedical Research Centre and by NIHR grants NIHR132240 (OPERA) and 16/61/10 (ORiF) to BO. Support was also provided by UKRI/MRC grants MR/W026813/1 and MR/Y010175/1 to AVa.