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. 2013 Nov;28(11):2207-15.
doi: 10.1007/s00467-013-2547-z. Epub 2013 Jul 15.

FGF23 and mineral metabolism in the early post-renal transplantation period

Katherine Wesseling-Perry  1 , Renata C Pereira, Eileen Tsai, Robert Ettenger, Harald Jüppner, Isidro B Salusky
Affiliations

FGF23 and mineral metabolism in the early post-renal transplantation period

Katherine Wesseling-Perry et al. Pediatr Nephrol. 2013 Nov.

Abstract

Background: The relationship between fibroblast growth factor 23 (FGF23) and vitamin D production and catabolism post-renal transplantation has not been characterized.

Methods: Circulating creatinine, calcium, phosphorus, albumin, parathyroid hormone, FGF23, and 1,25(OH)2 vitamin D (calcitriol) values were obtained pre-transplantation, daily post-operatively for 5 days, and at 6 months post-transplantation in 44 patients aged 16.4 ± 0.4 years undergoing renal transplantation at UCLA from 1 August 2005 through to 30 April 2007. 25(OH) Vitamin D and 24,25(OH)2 vitamin D concentrations were obtained at baseline and on post-operative days 5 and 180, and urinary concentrations of creatinine, phosphorus, and FGF23 were measured on post-operative days 1, 3, 5, and 180.

Results: Circulating phosphate concentrations declined more rapidly and the fractional excretion of phosphorus was higher in the first week post-transplantation in subjects with higher FGF23 values. Fractional excretion of FGF23 was low at all time-points. Circulating 1,25(OH)2 vitamin D levels rose more rapidly and were consistently higher in patients with lower FGF23 values; however, 25(OH) vitamin D and 24,25(OH)2 vitamin D values were unrelated to FGF23 concentrations.

Conclusions: Inhibition of renal 1α-hydroxylase, rather than stimulation of 24-hydroxylase, may primarily contribute to the relationship between FGF23 values and calcitriol. The rapid decline in FGF23 levels post-transplantation in our patient cohort was not mediated solely by the filtration of intact FGF23 by the new kidney.

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Figures

Figure 1
Figure 1
Plasma fibroblast growth factor 23 (FGF23) values in patients with pre-transplantation FGF23 concentrations below the median value (closed circles) as compared to patients with pre-transplantation FGF23 values above the median (open circles). The shaded area represents the normal range. FGF23 concentrations values declined over time (p<0.001) and subjects with higher pre-transplantation FGF23 values had higher post-transplantation values (p<0.001).
Figure 2
Figure 2
Total serum calcium values in patients with pre-transplantation fibroblast growth factor 23 (FGF23) concentrations below the median value (closed bars) as compared to patients with pre-transplantation FGF23 values above the median (open bars). The shaded area represents the normal range. Serum calcium concentrations increased with time (p<0.01) with a greater increase in subjects with higher pre-transplantation FGF23 values (p<0.001 for the interaction between time and pre-transplantation FGF23).
Figure 3
Figure 3
Circulating 1st PTH-IMA values in patients with pre-transplantation FGF23 concentrations below the median value (closed circles) as compared to patients with pre-transplantation FGF23 values above the median (open circles). The shaded area (value: 10-65 pg/ml) represents the normal range. Parathyroid hormone (PTH) levels declined in all subjects post-transplantation (p<0.05); no differences were observed based on pre-transplantation fibroblast growth factor (FGF23) values.
Figure 4
Figure 4
Serum phosphorus values in patients with pre-transplantation fibroblast growth factor 23 (FGF23) concentrations below the median value (closed bars) as compared to patients with pre-transplantation FGF23 values above the median (open bars). The shaded area represents the normal range. Serum phosphorus concentrations decreased over time (p<0.01) with a greater decline in patients with higher pre-transplantation FGF23 concentrations (p<0.001 for the interaction between time and pre-transplantation FGF23).
Figure 5
Figure 5
Fractional excretion of phosphate (FEPO4) values in patients with pre-transplantation FGF23 concentrations below the median value (closed bars) as compared to patients with pre-transplantation fibroblast growth factor 23 (FGF23) values above the median (open bars). The shaded area represents the normal range. Post-operative renal phosphate excretion was related to both pre-operative FGF23 (p<0.01) and time (p<0.001).
Figure 6
Figure 6
Circulating 1,25(OH)2vitamin D values in patients with pre-transplantation fibroblast growth factor 23 (FGF23) concentrations below the median value (closed bars) as compared to patients with pre-transplantation FGF23 values above the median (open bars). The shaded area represents the normal range. 1,25(OH)2vitamin D values increased with time (p<0.01) with a greater increase observed in subjects with higher baseline FGF23 concentrations (p<0.001 for the interaction between pre-operative FGF23 and time).
Figure 7
Figure 7
Western blot analysis of unconcentrated urine samples from 4 patients with “high” baseline FGF23 values and residual urine production pre-operatively, and on days 1, 3 and 5 after successful renal transplantation. Primary antibodies were directed against fibroblast growth factor 23 (FGF23)(51-69) (Panel A) and FGF23(225-244) (Panel B); an HRP-labeled secondary antibody was used for detection. The location of different protein size markers is as indicated. Urinary FGF23 concentrations, as detected by ELISA, ranged from 6650 (pt 2) to 77500 (pt 1) RU/ml on day 0 in the 4 patients. By day 5, urinary FGF23 concentrations ranged from 12 to 24 RU/ml in the 4 subjects.
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