Longitudinal FGF23 and Klotho axis characterization in children treated with chronic peritoneal dialysis

Cano, Francisco; Freundlich, Michael; Ceballos, María L; Rojo, Angélica; Azócar, Marta; Delgado, Iris; Ibacache, Maria Jose; Delucchi, Maria A; Lillo, Ana María; Irarrázabal, Carlos E.; Ugarte, Maria F.

doi:10.1093/ckj/sfu074

Cited by 22 publications

(19 citation statements)

References 48 publications

(83 reference statements)

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“…The decline in Klotho levels was associated with increased FGF23 and iPTH levels in this study [77]. Furthermore, serum Klotho levels in children on chronic peritoneal dialysis were significantly lower than in healthy controls [78]. …”

Section: Klotho Deficiency As a Biomarker For Ckdmentioning

confidence: 70%

Potential application of klotho in human chronic kidney disease

Neyra

2017

Bone

103

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The extracellular domain of transmembrane alpha-Klotho (αKlotho, hereinafter simply called Klotho) is cleaved by secretases and released into the circulation as soluble Klotho. Soluble Klotho in the circulation starts to decline early in chronic kidney disease (CKD) stage 2 and urinary Klotho possibly even earlier in CKD stage 1. Therefore soluble Klotho could serve as an early and sensitive marker of kidney function decline. Moreover, preclinical animal data support Klotho deficiency is not just merely a biomarker, but a pathogenic factor for CKD progression and extrarenal CKD complications including cardiovascular disease and disturbed mineral metabolism. Prevention of Klotho decline, re-activation of endogenous Klotho production or supplementation of exogenous Klotho are all associated with attenuation of renal fibrosis, retardation of CKD progression, improvement of mineral metabolism, amelioration of cardiomyopathy, and alleviation of vascular calcification in CKD. Therefore Klotho is not only a diagnostic and/or prognostic marker for CKD, but the treatment of Klotho deficiency may be a promising strategy to prevent, retard, and decrease the burden of comorbidity in CKD.

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Section: Klotho Deficiency As a Biomarker For Ckdmentioning

confidence: 70%

Potential application of klotho in human chronic kidney disease

Neyra

2017

Bone

103

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“…The adjusted decrease in serum Klotho was 3.2 pg/mL for each 1 mL/min/ 1.73 m 2 decrease in eGFR [33] . In children under peritoneal dialysis, serum Klotho levels were also significantly lower than in healthy controls [54] .…”

Section: Klotho Deficiency In Ckdmentioning

confidence: 78%

Klotho/FGF23 Axis in Chronic Kidney Disease and Cardiovascular Disease

2016

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FGF23 may also contribute to CVD. Prevention of Klotho decline, reactivation of endogenous Klotho production, or supplementation of exogenous Klotho attenuate renal fibrosis, retard CKD progression, improve mineral metabolism, ameliorate cardiomyopathy, and alleviate vascular calcification in CKD. However, the poor CVD outcome after depletion of FGF23 with FGF23 antibody stimulates the generation of a more specific inhibitor of FGF23 for CKD treatment. Key Message: Klotho/FGF23 may not only be diagnostic and/or prognostic biomarkers for CKD and CVD, but are also pathogenic contributors to CKD progression and CVD development. The Klotho/FGF23 axis should be a novel target for renal clinics.

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“…In patients with CKD, whether adults or children, dialysis dependent or not, no clear relationship has been established between sKl and FGF-23 [15–20]. Only one study, by Rotondi et al .…”

Section: Discussionmentioning

confidence: 99%

Soluble klotho may be a marker of phosphate reabsorption

Tan¹,

Smith²,

Holt³

et al. 2017

Clinical Kidney Journal

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Background: Membrane-bound α-klotho functions as a co-receptor with fibroblast growth factor receptor at the renal tubule conferring specificity to fibroblast growth factor-23 (FGF-23), allowing it to inhibit tubular phosphate reabsorption at physiological concentrations. α-klotho also exists as a soluble protein. However, the complex interrelationships between soluble α-klotho (sKl), FGF-23 and phosphate reabsorption are poorly understood, with little known about the links between sKl, FGF-23 and phosphate reabsorption in chronic kidney disease (CKD). This study addresses this issue in a cohort of patients with and without CKD. Methods: We conducted a single-centre, cross-sectional study of contemporaneously obtained samples of blood and 24-h urine biochemistry along with sKl and intact FGF-23 (iFGF-23) from non–dialysis-dependent CKD patients and healthy volunteers. Pearson’s correlation coefficients were used to determine correlations between natural log-transformed (Ln) sKl and iFGF-23 with other parameters of interest. Backward multivariate analysis was undertaken to evaluate the relationship between mineral parameters. Results: One hundred and sixteen participants (77 with CKD and 39 healthy volunteers) were studied, of which 74 (63.8%) were male. The median age was 61 (interquartile range 49–71) years. Those with CKD had lower sKl (408 versus 542 pg/mL), higher iFGF-23 (94 versus 41 pg/mL), higher fractional excretion of phosphate (25.05 versus 10.98%) and lower daily urinary phosphate excretion (UPE) (24.8 versus 32.3 mmol/L) compared with healthy volunteers (all P ≤ 0.002). Age correlated inversely and estimated glomerular filtration rate (eGFR) correlated positively with phosphate reabsorption and Ln(sKl), while the opposite was seen with Ln(iFGF23). Upon multivariate analysis, eGFR, Ln(sKl) and parathyroid hormone were independently associated with phosphate reabsorption, whereas Ln(iFGF-23) was not, after adjustment for age. Conclusions: Abnormalities in phosphate regulatory pathways are disturbed early in CKD. While iFGF-23 is associated with phosphate excretion on univariate analyses, sKl demonstrates a significant association with phosphate reabsorption independent of iFGF-23, and this relationship deserves further exploration.

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Longitudinal FGF23 and Klotho axis characterization in children treated with chronic peritoneal dialysis

Cited by 22 publications

References 48 publications

Potential application of klotho in human chronic kidney disease

Potential application of klotho in human chronic kidney disease

Klotho/FGF23 Axis in Chronic Kidney Disease and Cardiovascular Disease

Soluble klotho may be a marker of phosphate reabsorption

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