Fibroblast growth factor <scp>23‐Klotho</scp> and mineral metabolism in the first year after pediatric kidney transplantation: A single‐center prospective study

Kubota, Masashi; Hamasaki, Yuko; Hashimoto, Junya; Aoki, Yujiro; Kawamura, Takeshi; Saito, Akinobu; Yuasa, Rena; Muramatsu, Masaki; Komaba, Hirotaka; Toyoda, Masao; Fukagawa, Masafumi; Shishido, Seiichirou; Sakai, Ken

doi:10.1111/petr.14440

Cited by 4 publications

(2 citation statements)

References 45 publications

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“… 42 One study showed that Klotho levels 7 d and 1 mo posttransplant were similar to Klotho levels before transplantation, but levels started to rise approximately 4 mo posttransplant. 45 Another study on long-term surviving kidney transplant recipients (>10 y after transplantation) showed a nonsignificant decline in Klotho levels 43 ; this might be as expected from 10 y of aging.…”

Section: Discussionmentioning

confidence: 89%

Klotho and Fibroblast Growth Factor 23 Are Independent of Vitamin D, and Unlike Vitamin D, Are Not Associated With Graft- and Patient Survival After Kidney Transplantation

Thorsen

Bleskestad

Åsberg

et al. 2023

Transplantation Direct

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Background. Short-term survival after kidney transplantation is excellent but long-term survival remains suboptimal. The aim of the study was to explore the relationship between soluble α-Klotho (sKlotho) and intact fibroblast growth factor 23 (iFGF23) measured 8 wk and 1 y posttransplant with long-term graft- and patient survival in a cohort of kidney transplant recipients with deficient and nondeficient vitamin D (25[OH]D) levels. Methods. Vitamin D, sKlotho, and iFGF23 were measured 8 wk and 1 y posttransplant in 132 recipients transplanted between November 2012 and October 2013. Results. Of the 132 kidney transplant recipients, 49 had deficient vitamin D levels (<30 nmol/L) and 83 had nondeficient vitamin D levels (≥30 nmol/L) at 8 wk posttransplant. The mean age was 51 y and the median follow-up was 7.4 y. At 1 y posttransplant, vitamin D increased significantly. There were no significant differences in sKlotho or iFGF23 levels between the 2 vitamin D groups neither at 8 wk nor 1 y. sKlotho increased significantly and iFGF23 decreased significantly in the whole cohort. During the follow-up, there were 36 graft losses (27%) and 27 deaths (20%). Ninety-four percent of the transplant recipients with nondeficient vitamin D levels were alive with a well-functioning graft after 5 y using Kaplan-Meier survival estimates, compared with 84% of the patients with deficient vitamin D levels (P = 0.014). Klotho and FGF23 levels did not influence graft- and patient survival. Conclusions. In this nationwide cohort of kidney transplant recipients, long-term graft- and patient survival were significantly better in patients with vitamin D ≥30 nmol/L 8 wk posttransplant compared with those with vitamin D <30 nmol/L. sKlotho levels increased and iFGF23 levels decreased from 8 wk to 1 y posttransplant. Klotho and FGF23 levels were not associated with graft- and patient survival.

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Section: Discussionmentioning

confidence: 89%

Klotho and Fibroblast Growth Factor 23 Are Independent of Vitamin D, and Unlike Vitamin D, Are Not Associated With Graft- and Patient Survival After Kidney Transplantation

Thorsen

Bleskestad

Åsberg

et al. 2023

Transplantation Direct

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“…The FGF23 gene is a member of a large family of fibroblast growth factors [94], which is most associated with the KLOTHO gene in anti-aging processes [95]. A number of publications have examined the relationship of FGF23 and KLOTHO genes in physiological processes and in various diseases [96][97][98][99][100][101][102][103][104]. In this regard, we studied the possible effect of piRNA on the expression of the FGF23 gene.…”

Section: Resultsmentioning

confidence: 99%

piRNAs and miRNAs Can Bind to mRNA of <i>KLOTHO</i> and <i>FGF23</i> Genes

Ivashchenko,

Akhmetova,

Zhanuzakov

et al. 2023

Preprint

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The problem of increasing life expectancy is solved with the help of many medical and social areas. It has been established that piRNAs and miRNAs can significantly modify the expression of protein-coding genes by suppressing the translation process. The aim of this work was to establish the possibility of binding piRNAs and miRNAs with mRNA of the KLOTHO and FGF23 genes, which promote health and increase life expectancy through participation in key metabolic processes. We used the MirTarget program, which determines the quantitative characteristics of complementary interactions of all piRNAs and miRNAs nucleotides with mRNA of the genes. piR-44682, piR-1940042, piR-3008660, piR-3215034, piR-6885965, piR-7980636 and one miRNA (ID00756.3p-miR) binding to the mRNA of the KLOTHO gene were found in one cluster of binding sites (BSs). piRNA-6890096 interacted with the mRNA of KLOTHO gene in a fully complementary manner using only canonical nucleotides. Among 17494 human genes, target genes interacting with five piRNAs that bind to the mRNA of KLOTHO gene were identified. mRNA of the AFF2, BCL2L11, CPT1A, DAZAP1, NDRG3, SKIDA1, WBP4, ZIC5, ZSWIM6 genes interacted with piR-3215034 and piR-6885965, which formed clusters of BSs located in 5'UTR, CDS and 3'UTR. The piR-576442, piR-1501557, piR-1845735, piR-2069834, and piR-3029987 had BSs in the mRNAs of the FGF23 gene, located only in the 3'UTR. It is proposed to use piRNAs and miRNAs as regulators of the expression of KLOTHO and FGF23 anti-aging genes.

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The Klotho protein and FGF23 as well-known players in the aging process but underestimated in the process of individual development and selected diseases of childhood and adolescence – a systematic review

Wiernik,

Hyla-Klekot,

Brauner

et al. 2024

Pediatr Med Rodz

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Introduction and objective: The FGF23–Klotho endocrine axis plays a pivotal role not only in processes associated with aging but also in metabolic pathways, with implications for paediatric disorders. The aim of this study was to systematically review the existing literature on Klotho and FGF23 in the paediatric population. Materials and methods: Based on the PubMed and Web of Science databases, we conducted a PRISMA-guided search using (klotho) AND (children); (FGF23) AND (children), adhering strictly to the PRISMA guidelines, and assessed evidence quality. Results: The systematic review included 66 studies. Altered Klotho and FGF23 serum levels were observed in paediatric metabolic conditions (chronic kidney disease, diabetes), cardiovascular, and growth and musculoskeletal disorders. In some of them, Klotho and FGF23 serum levels changed with disorder treatment. Elevated FGF23 and Klotho deficiency in renal failure adversely impacted the cardiovascular system. Lower Klotho levels were found in preterm neonates, especially with bronchopulmonary dysplasia. Early Klotho supplementation in a bronchopulmonary dysplasia model mitigated lung tissue changes and improved the cardiac function. Children with lower Klotho levels undergoing cardiac surgeries faced a higher risk of postoperative complications, especially acute kidney injury. In X-linked hypophosphataemia, excess FGF23 led to musculoskeletal consequences. FGF23 serum levels aided the diagnosis of hypophosphataemic rickets, and anti-FGF23 antibody emerged as a common X-linked hypophosphataemia treatment. Conclusions: Klotho and FGF23 serve as promising early markers for paediatric metabolic disorders, offering a valuable tool for assessing complication risks. Klotho supplementation holds promise as a treatment method for specific paediatric disorders, while anti-FGF23 antibody is already established in X-linked hypophosphataemia treatment.

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Fibroblast growth factor 23‐Klotho and mineral metabolism in the first year after pediatric kidney transplantation: A single‐center prospective study

Cited by 4 publications

References 45 publications

Klotho and Fibroblast Growth Factor 23 Are Independent of Vitamin D, and Unlike Vitamin D, Are Not Associated With Graft- and Patient Survival After Kidney Transplantation

Klotho and Fibroblast Growth Factor 23 Are Independent of Vitamin D, and Unlike Vitamin D, Are Not Associated With Graft- and Patient Survival After Kidney Transplantation

piRNAs and miRNAs Can Bind to mRNA of <i>KLOTHO</i> and <i>FGF23</i> Genes

The Klotho protein and FGF23 as well-known players in the aging process but underestimated in the process of individual development and selected diseases of childhood and adolescence – a systematic review

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