The Role of Alterations in Alpha-Klotho and FGF-23 in Kidney Transplantation and Kidney Donation

Meera Gupta, Gabriel Orozco, Madhumati Rao, Roberto Gedaly, Hartmut H. Malluche, Javier A. Neyra

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations


Cardiovascular disease and mineral bone disorders are major contributors to morbidity and mortality among patients with chronic kidney disease and often persist after renal transplantation. Ongoing hormonal imbalances after kidney transplant (KT) are associated with loss of graft function and poor outcomes. Fibroblast growth factor 23 (FGF-23) and its co-receptor, α-Klotho, are key factors in the underlying mechanisms that integrate accelerated atherosclerosis, vascular calcification, mineral disorders, and osteodystrophy. On the other hand, kidney donation is also associated with endocrine and metabolic adaptations that include transient increases in circulating FGF-23 and decreases in α-Klotho levels. However, the long-term impact of these alterations and their clinical relevance have not yet been determined. This manuscript aims to review and summarize current data on the role of FGF-23 and α-Klotho in the endocrine response to KT and living kidney donation, and importantly, underscore specific areas of research that may enhance diagnostics and therapeutics in the growing population of KT recipients and kidney donors.

Original languageEnglish
Article number803016
JournalFrontiers in Medicine
StatePublished - May 6 2022

Bibliographical note

Funding Information:
The authors wish to acknowledge the invaluable contributions to this research from our participants and their families; the staff of UNC Global Projects Zambia; and the local community advisory boards in Lusaka. The research presented in this article was funded by the Bill and Melinda Gates Foundation (OPP1033514), through a grant to the Global Alliance to Prevent Prematurity and Stillbirth. Additional support was provided by the US National Institutes of Health through the UNC Center for AIDS Research (P30 AI50410). Trainee support has been provided through the US National Institutes of Health for J.T.P. (T32 HD075731 and K01 TW010857) and K.J.R. (D43 TW009340). J.T.P. also receives funding from the Burroughs Wellcome Fund Next Gen Pregnancy Initiative (NGP 10161). J.R. and M.F. were supported by the Bill and Melinda Gates Foundation (OPP1189217), through the Vaginal Microbiome Research Consortium (VMRC). B.M. was supported by NIDDK (R21DK123674), NHLBI (R01HL148672), and The Gerber Foundation (6361). The conclusions and opinions expressed in this article are those of the authors and do not necessarily reflect those of the funders. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Publisher Copyright:
Copyright © 2022 Gupta, Orozco, Rao, Gedaly, Malluche and Neyra.


  • ESKD (end stage kidney disease)
  • FGF-23
  • alpha-Klotho
  • bone mineral density (BMD)
  • cardiovascular disease
  • kidney donation
  • kidney transplant
  • mineral bone disease

ASJC Scopus subject areas

  • Medicine (all)


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