UCSF

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.