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

Abstract

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.