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Effects of acute kidney injury and chronic hypoxemia on fibroblast growth factor 23 levels in pediatric cardiac surgery patients

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Abstract

Background

Fibroblast growth factor-23 (FGF23) levels are elevated in cardiopulmonary bypass (CPB)-associated acute kidney injury (AKI); however, it is unknown how much of the circulating FGF23 is intact and bioactive. Hypoxia may induce FGF23 production, yet its impact in humans is unknown. Pediatric cardiac surgery patients have both a high incidence of CPB-associated AKI and a high prevalence of chronic hypoxemia.

Methods

We assessed the effects of hypoxemia and CPB-associated AKI on C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels in 32 pediatric cardiac surgery patients with normal estimated glomerular filtration rate (eGFR). Plasma cFGF23 and iFGF23 were measured preoperatively and serially postoperatively.

Results

Despite normal renal and ventricular function, preoperative cFGF23 levels were high and elevated out of proportion to iFGF23 levels. Preoperative oxygen saturation measurements correlated inversely with FGF23 levels. Preoperative cFGF23 and oxygen saturation both predicted postoperative AKI. Postoperatively, cFGF23 and iFGF23 increased by 2 h postreperfusion; iFGF23 then returned to baseline, but cFGF23 remained elevated through 24 h postreperfusion. Group status (AKI vs. non-AKI) modified the effect of time on changes in iFGF23 levels but not cFGF23 levels.

Conclusions

Preoperative cFGF23 may predict CPB-associated kidney dysfunction. Changes over time in cFGF23 and iFGF23 levels post-CPB differ. Chronic hypoxemia may affect FGF23 production in humans.

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Acknowledgments

This work was supported in part by USPHS Grants DK-67563, DK-35423, DK-80984; CTSI Grant UL1 TR-000124; NIH K12 Child Health Research Career Development Award K12-HD-034610; NIH Training Grant T32-DK-07789; funds from the UCLA Children’s Discovery and Innovation Institute, and funds from the American Society of Nephrology Norman Siegel Foundation. This work was presented as a poster abstract at the American Society of Nephrology’s Kidney Week, 7 November 2013, Atlanta, Georgia. FGF23 and PTH kits were kindly provided by Immutopics International.

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Correspondence to Mark R. Hanudel.

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The study was approved by the UCLA Institutional Review Board, and informed consent and assent were obtained from parents and patients accordingly.

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The authors declare no conflict of interest.

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Hanudel, M.R., Wesseling-Perry, K., Gales, B. et al. Effects of acute kidney injury and chronic hypoxemia on fibroblast growth factor 23 levels in pediatric cardiac surgery patients. Pediatr Nephrol 31, 661–669 (2016). https://doi.org/10.1007/s00467-015-3257-5

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