Plasma soluble αKlotho, serum fibroblast growth factor 23, and mobility disability in community-dwelling older adults

Michelle Shardell, David A. Drew, Richard D. Semba, Tamara B. Harris, Peggy M. Cawthon, Eleanor M. Simonsick, Rita R. Kalyani, Ann V. Schwartz, Stephen B. Kritchevsky, Anne B. Newman

Research output: Contribution to journalArticlepeer-review


Context: αKlotho is a hormone and co-receptor for fibroblast growth factor 23 (FGF23), a hormone that downregulates active vitamin D synthesis and promotes phosphate excretion. Low αKlotho and high FGF23 occur in chronic kidney disease (CKD). Objective: We aimed to assess the relationships of αKlotho and FGF23 with mobility disability in community-dwelling older adults. Design and Setting: We estimated associations of plasma-soluble αKlotho and serum FGF23 concentrations with mobility disability over 6 years. Additional analyses was stratified by CKD. Participants: Participants included 2751 adults (25.0% with CKD), aged 71 to 80 years, from the 1998 to 1999 Health, Aging, and Body Composition Study visit. Main Outcome Measures: Walking disability and stair climb disability were defined as self-reported “a lot of difficulty” or an inability to walk a quarter mile and climb 10 stairs, respectively. Results: Median (interquartile range [IQR]) serum FGF23 and plasma soluble αKlotho concentrations were 46.6 (36.7, 60.2) pg/mL and 630.4 (478.4, 816.0) pg/mL, respectively. After adjustment, higher αKlotho concentrations were associated with lower walking disability rates (Rate Ratio [RR] highest vs. lowest tertile = 0.74; 95% confidence interval l [CI] = 0.62, 0.89; P = 0.003). Higher FGF23 concentrations were associated with higher walking disability rates (RR highest vs. lowest tertile = 1.24; 95%CI = 1.03, 1.50; P = 0.005). Overall, higher αKlotho combined with lower FGF23 was associated with the lowest walking disability rates (P for interaction = 0.023). Stair climb disability findings were inconsistent. No interactions with CKD were statistically significant (P for interaction > 0.10). Conclusions: Higher plasma soluble αKlotho and lower serum FGF23 concentrations were associated with lower walking disability rates in community-dwelling older adults, particularly those without CKD. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (, which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact

Original languageEnglish (US)
JournalJournal of the Endocrine Society
Issue number5
StatePublished - May 1 2020


  • Aging
  • Chronic kidney disease
  • Fibroblast growth factor 23
  • Mobility disability
  • αKlotho

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism


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