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Kidney Week

Abstract: PO0621

Phosphate and Fibroblast Growth Factor 23 Are Mediators of Lung Injury in CKD

Session Information

  • CKD Mechanisms - 1
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Bollenbecker, Seth, University of Alabama at Birmingham, Division of Pulmonary, Allergy, and Critical Care Medicine, Birmingham, Alabama, United States
  • Czaya, Brian A., University of Alabama at Birmingham, Division of Nephrology, Birmingham, Alabama, United States
  • Easter, Molly, University of Alabama at Birmingham, Division of Pulmonary, Allergy, and Critical Care Medicine, Birmingham, Alabama, United States
  • Kentrup, Dominik, University of Alabama at Birmingham, Division of Nephrology, Birmingham, Alabama, United States
  • Barnes, Jarrod W., University of Alabama at Birmingham, Division of Pulmonary, Allergy, and Critical Care Medicine, Birmingham, Alabama, United States
  • Faul, Christian, University of Alabama at Birmingham, Division of Nephrology, Birmingham, Alabama, United States
  • Krick, Stefanie, University of Alabama at Birmingham, Division of Pulmonary, Allergy, and Critical Care Medicine, Birmingham, Alabama, United States
Background

Although well-documented in chronic kidney disease (CKD), the role of phosphate in pulmonary pathology is not widely known. Phosphorus, or phosphate in its oxidized circulating form, is normally removed from the body by healthy kidneys. CKD disrupts this process, leading to hyperphosphatemia in later stages. We have shown that fibroblast growth factor 23 (FGF23), a key regulator of phosphate metabolism, is elevated in inflammatory lung diseases; that increase in FGF23 contributes to unfavorable clinical outcomes. To improve outcomes for patients with concomitant CKD and pulmonary disease, we wanted to examine direct actions of phosphate and FGF23 and their potential underlying mechanisms.

Methods

For in vitro experiments, human lung fibroblasts were treated with 0 to 5 mM sodium phosphate. Expression levels of interleukin (IL)-8 and collagen (COL)1A1 were analyzed by qPCR. Cell counts and viability were quantified with trypan blue staining. In vivo, we placed C57Bl/6 mice on a high phosphate (3%) diet to elevate serum phosphate levels in absence of kidney injury and administered bleomycin via oropharyngeal aspiration to generate an acute pulmonary inflammatory response. Serum FGF23 levels were measured by ELISA and serum analysis for phosphate and renal function were obtained. Expression of FGF23 pathway and inflammatory markers were analyzed in murine lung and kidney tissue using qPCR and western blotting.

Results

Augmented phosphate concentrations increased IL-8 and COL1A1 expression from human lung fibroblasts with a concomitant reduction in overall cell number. Serum FGF23 levels were significantly upregulated in mice on a high phosphate diet and further increased in these mice when exposed to bleomycin. Serum phosphate and creatinine levels were significantly elevated. High phosphate and bleomycin increased local FGF23 expression in murine lung tissue.

Conclusion

Upregulation of FGF23 in response to bleomycin during a high phosphate diet suggests that inflammation induced by primary lung injury is worsened by systemic elevation of serum phosphate levels. Our data suggest that in CKD, high serum phosphate levels may increase susceptibility and progression of lung injury. Our results indicate that the existence of a pulmo-renal crosstalk is exaggerating pulmonary injury.