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. 2015:2015:872193.
doi: 10.1155/2015/872193. Epub 2015 Mar 19.

Soluble α -Klotho Serum Levels in Chronic Kidney Disease

Silverio Rotondi  1 , Marzia Pasquali  1 , Lida Tartaglione  1 , Maria Luisa Muci  1 , Giusy Mandanici  1 , Cristiana Leonangeli  1 , Silvia Sales  1 , Alessio Farcomeni  2 , Sandro Mazzaferro  1
Affiliations

Soluble α -Klotho Serum Levels in Chronic Kidney Disease

Silverio Rotondi et al. Int J Endocrinol. 2015.

Abstract

Transmembrane α-Klotho (TM-Klotho), expressed in renal tubules, is a cofactor for FGF23-receptor. Circulating soluble-α-Klotho (s-Klotho) results from TM-Klotho shedding and acts on Phosphate (P) and Calcium (Ca) tubular transport. Decreased TM-Klotho, described in experimental chronic kidney disease (CKD), prevents actions of FGF23 and lessens circulating s-Klotho. Thus, levels of s-Klotho could represent a marker of CKD-MBD. To evaluate the clinical significance of s-Klotho in CKD we assayed serum s-Klotho and serum FGF23 in 68 patients (age 58 ± 15; eGFR 45 ± 21 mL/min). s-Klotho was lower than normal (519 ± 183 versus 845 ± 330 pg/mL, P < .0001) in renal patients and its reduction was detectable since CKD stage 2 (P < .01). s-Klotho correlated positively with eGFR and serum calcium (Cas) and negatively with serum phosphate (Ps), PTH and FGF23. FGF23 was higher than normal (73 ± 51 versus 36 ± 11, P < .0002) with significantly increased levels since CKD stage 2 (P < .001). Our data indicate a negative effect of renal disease on circulating s-Klotho starting very early in CKD. Assuming that s-Klotho mirrors TM-Klotho synthesis, low circulating s-Klotho seems to reflect the ensuing of tubular resistance to FGF23, which, accordingly, is increased. We endorse s-Klotho as an early marker of CKD-MBD.

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Figures

Figure 1
Figure 1
Correlation test of s-Klotho levels with FGF23 levels in CKD.
Figure 2
Figure 2
Correlation tests of eGFR with s-Klotho levels (a) and FGF23 (b).
Figure 3
Figure 3
s-Klotho (soluble Klotho) (a) and FGF23 (fibroblast growth factor 23) and (b) serum levels stratified by CKD stage and compared with reference values. Indicated are medians, first and third quartiles, minimal and maximal values. Values between 1.5 and 3 times IQR above the third quartile or below the first are represented by circles. Wilcoxon rank-sum tests. KDOQI: National Kidney Foundation Disease Outcomes Quality Initiative clinical practice guidelines [15]. # P < .01 versus reference value; * P < .001 versus reference value; § P < .002 versus reference value.
Figure 4
Figure 4
Correlation tests of s-Klotho levels with: (a) PTH, (b) Ps, (c) Cas.
Figure 5
Figure 5
Correlation tests of FGF23 with: (a) PTH, (b) Ps, (c) 1,25D, (d) FEPO4.
See this image and copyright information in PMC

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