Title |
Klotho in pregnancy and intrauterine development – Potential clinical implications: a review from the European Renal Association CKD-MBD Working Group
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Published in |
Nephrology Dialysis Transplantation, March 2024
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DOI | 10.1093/ndt/gfae066 |
Pubmed ID | |
Authors |
Mehmet Kanbay, Ali Mutlu, Cicek N Bakir, Ibrahim B Peltek, Ata A Canbaz, Juan Miguel Díaz Tocados, Mathias Haarhaus |
Abstract |
Intrauterine development is crucial for life-long health; therefore, elucidation of its key regulators is of interest for their potential prognostic and therapeutic implications. Originally described as a membrane-bound anti-aging protein, Klotho has evolved as a regulator of numerous functions in different organ systems. Circulating Klotho is generated by alternative splicing or active shedding from cell membranes. Recently, Klotho was identified as a regulator of placental function, and while Klotho does not cross the placental barrier, increased levels of circulating α-Klotho have been identified in umbilical cord blood compared to maternal blood, indicating that Klotho may also play a role in intrauterine development. In this narrative review, we discuss novel insights into the specific functions of the Klotho proteins in the placenta and in intrauterine development, while summarizing up-to-date knowledge about their structures and functions. Klotho plays a role in stem cell functioning, organogenesis, and haematopoiesis. Low circulating maternal and foetal levels of Klotho are associated with preeclampsia, intra-uterine growth restriction, and an increased perinatal risk for newborns, indicating a potential used of Klotho as biomarker and therapeutic target. Experimental administration of Klotho protein indicates a neuro- and nephroprotective potential, suggesting a possible future role of Klotho as a therapeutic agent. However, the use of Klotho as intervention during pregnancy is yet unproven. Here, we summarize novel evidence, suggesting Klotho as a key regulator for healthy pregnancies and intrauterine development with promising potential for clinical use. |
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Country | Count | As % |
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India | 8 | 18% |
Mexico | 6 | 14% |
United Kingdom | 3 | 7% |
Nepal | 1 | 2% |
Argentina | 1 | 2% |
Ecuador | 1 | 2% |
Turkey | 1 | 2% |
Colombia | 1 | 2% |
Ukraine | 1 | 2% |
Other | 4 | 9% |
Unknown | 17 | 39% |
Demographic breakdown
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Members of the public | 34 | 77% |
Scientists | 7 | 16% |
Practitioners (doctors, other healthcare professionals) | 2 | 5% |
Science communicators (journalists, bloggers, editors) | 1 | 2% |