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Abstract: FR-PO158

Zinc Supplementation for 3 Months Increases Serum Levels of C-Terminal FGF-23 in Zinc-Deficient Children with CKD

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Belostotsky, Vladimir, McMaster Children's Hospital, Hamilton, Ontario, Canada
  • Moore, Caroline, Dept of Pediatrics, McMaster University, Hamilton, Ontario, Canada
  • Ma, Julia H., McMaster University, Hamilton, Ontario, Canada
  • Arora, Steven, McMaster Children's Hospital, Hamilton, Ontario, Canada
  • Atkinson, Stephanie A., McMaster University, Hamilton, Ontario, Canada
  • Filler, Guido, London Health Sciences Centre, London, Ontario, Canada
Background

Chronic Kidney Disease (CKD) has been associated with increased fibroblast growth factor 23 (FGF23), decreased Klotho concentrations and subclinical zinc (Zn) deficiency (Fukushima 2019). FGF23 promotes phosphate clearance but is dependent on Klotho expression by tubular cells. In animal models Zn supplementation stimulates Klotho production (Morishita 2001) and reduces vascular calcification, frequently seen in CKD (Voelkl 2018). This study investigated whether 3 months of Zn therapy corrects the deficiency in CKD and leads to changes in circulating FGF23 and Klotho concentrations.

Methods

Children with primary CKD and CKD secondary to declining function of kidney transplant from two tertiary pediatric nephrology centers in Southern Ontario, Canada were screened for Zn deficiency (plasma Zn < 11.5 μmol/L). Deficient children were treated with Zn citrate tablets (10 mg Zn/day for age 4-8 yr and 20 mg/day for age 9-18 yr) for 3 months. Plasma Zn was measured at baseline and 3 months by High Resolution Magnetic Sector Inductively Coupled Plasma Mass Spectrometry. Serum c-terminal FGF23 (cFGF23, Biomedica) and human soluble alpha-Klotho (TECO medical) were measured by ELISA, serum 25-hydroxyvitamin D (25-OHD) by LC/MS-MS (Waters). Paired t-tests and Wilcoxon tests were performed for normally and non-normally-distributed data, respectively. Children taking calcitriol were excluded from the final analysis due to its significant impact on FGF23 and Klotho metabolism.

Results

Table 1

Conclusion

In most patients we observed changes toward normal levels of Zn following three months of Zn supplementation in Zn deficient children with CKD (p=0.028). The concentration of cFGF23 also increased (p=0.008) while no change was observed in the level of Klotho. 25-OHD levels remained stable and did not affect the results. Either higher Zn doses or longer treatment may be needed before changes in Klotho might be seen.

Table 1 - Results
Biomarker,
mean ± SD or
median (25th – 75th percentiles)
 No treatment (zinc sufficient)
N=14
  Zinc citrate treatment
N=11
 
 Baseline3 monthsp-valueBaseline3 monthsp-value
Zn μmol/L12.6 (12.3-13.2)11.9 (11.1-12.6)0.19610.3 (9.8-10.9)11.8 (10.8-13.2)0.028
cFGF23 (pmol/L)1.2 (0.8-2.6)2.1 (1.3-3.0)0.3202.2 ± 1.63.4 ± 2.70.008
Klotho (pg/mL)1012 (646-1719)713 (594-1678)0.542826 ± 445812 ± 5020.370
25-OHD (nmol/L)73.7 ± 22.770.4 ± 18.70.52261.1 (55.9-74.2)67.5 (63.8-76.1)0.426

Funding

  • Other NIH Support