Elevated plasma c-terminal fibroblast growth factor, but not intact FGF23 or soluble Klotho, is associated with left ventricular hypertrophy in pediatric chronic hemodialysis patients

Shweta Shah; Eileen Brewer; Poyyapakkam Srivaths

doi:10.1530/boneabs.4.P12

Background: Cardiovascular disease is the leading cause of death in pediatric (ped) and adult ESRD patients. Left ventricular hypertrophy (LVH) is an independent predictor of mortality in ESRD. Besides traditional risk factors, such as high BP & fluid overload, high plasma FGF23 is associated with LVH in adult ESRD patients. Little is known about Kl, the renally produced cofactor of FGF23 for phosphorus (P) homeostasis. We studied ped HD patients for risk factors for LVH, including plasma FGF23 & soluble Klotho (sKl).

Methods: Cross-sectional study of 22 patients (16 males), 12–25 years old, HD 3 × per week, vintage 48±34 m, spKt/V 1.6±0.2; eight were anuric. BP & central BP (CBP, pulse wave tonometry) were obtained pre, intra and post-HD. ECHO for study was compared to ECHO within 1y; LVMI normalized for ht was used for LVH comparisons. Routine serum Ca, P, iPTH & 25OH-vit D were noted. Plasma c-terminal (c) FGF23, intact (i) FGF23 & sKl were measured by ELISA in patients; c-terminal fibroblast growth factor (cFGF23) & sKl were measured in 27 age-matched controls (ctl).

Results: cFGF23 was 1.3–2× higher than intact FGF23 (iFGF23) (cFGF23 100.919 RU/ml (IQR: 5.792; 315.934) vs iFGF23 75.520 pg/ml (2.734; 229.172) P=0.03) & positively (pos) correlated with iFGF23 (r=0.9, P=0.00001); both were much higher than cFGF23 for ctl (28 RU/ml (11; 45), P=0.002).sKl (557 pg/ml (412; 1072)) was no different vs ctl (685 (496, 1161), NS). Log cFGF23 & log iFGF23 pos correlated with serum P & Ca (r=0.5–0.6, P<0.01), negatively correlated with 25OH-vit D (r=−0.4, P<0.05) & were higher in anurics (P=0.04). Log cFGF23, but not log iFGF23 pos correlated with CBP & pre-HD systolic BP%ile for age/gender/ht (r=0.4, P<0.05). patients with log cFGF23 >50%ile from median had significantly elevated serum P, Ca, & LVMI (table; median (IQR)). patients with worsening LVMI from previous 1y had higher log cFGF23 (χ², P=0.02).

Table 1
Log cFGF23	Vintage m	Ca mg/dl	P mg/dl	iPTH pg/ml	25OH-Vit-D ng/ml	LVMI g/m^2.7	sKl pg/ml
<50%ile	32	9.25	5.1	343	27.5	34	972
n=10	(26.42)	(9.1,9.7)	(4.8,6.5)	(157,660)	(18.7,32.6)	(31,40)	(491,1090)
>50%ile	41	10.2	7.4	183	20.8	45	502
n=12	(22.86)	(10,10.8)	(6.7,8.1)	(150,417)	(15.5,31.6)	(40,53)	(393,673)
P value	NS	0.004	0.016	NS	NS	0.048	NS

Conclusion Compared to ctl, plasma FGF23 by either c or i method in ped HD patients is very high (>1000 fold) while sKl is no different. cFGF23 is significantly higher than and pos correlates with iFGF23. Not only Serum P pos but also serum Ca pos correlate with both cFGF23 and iFGF23, whereas higher cFGF23 was associated in this study with LVH (higher LVMI, worsening LVMI). Serum Ca in addition to P influences FGF23. FGF23 may be a ped HD cardiovascular risk factor, independent of sKl, but differences between cFGF23 and iFGF23 assay should be considered in future studies to be sure of CV risk categorization.: Disclosure

The authors declared no competing interests.

Bone Abstracts

P12