Associations between the concentrations of α-klotho and selected perfluoroalkyl substances in the presence of eGFR based kidney function and albuminuria: Data for US adults aged 40-79 years.

Exposures to per- and polyfluoroalkyl substances (PFAS) cause oxidative stress, a risk factor for tissue damage leading to kidney and cardiovascular diseases. The antiaging protein klotho is known to act as an anti-oxidative agent, and how klotho homeostasis interacts with PFAS has not been reported. This study among 3981 US adults aged 40-79 years old evaluated relationships of internal PFAS contamination to α-klotho across stages of estimated glomerular filtration rate or eGFR-based kidney function and albuminuria defined as urinary albumin creatinine ratio of >30 mg/g creatinine. In the absence of albuminuria and when eGFR based kidney function was in stage GF-1 (eGFR ≥ 90 mL/min/1.73 m), statistically significant inverse associations between α-klotho and PFNA (β = -0.04930, p < 0.01), PFDA (β = -0.03307, p = 0.02), and PFUnDA (β = -0.03451, p = 0.01), PFHxS (β = -0.03011, p = 0.04) and PFOS (β = -0.03126, p = 0.03) were noted. No associations between α-klotho and PFAS were observed when kidney function was in stages GF-2 (60 ≤ eGFR < 90 mL/min/1.73 m) or GF-3A (45 ≤ eGFR < 60 mL/min/1.73 m) in the presence or absence of albuminuria. Unexpectedly, however, in the absence of albuminuria, with kidney function in stage GF-3B/4 (15 ≤ eGFR < 45 mL/min/1.73 m), associations were positive between α-klotho and PFOA (β = 0.20989, p < 0.01), PFNA (β = 0.18373, p < 0.1), PFDA (β = 0.20413, p < 0.01), PFUnDA (β = 0.17660, p < 0.01), and PFOS (β = 0.14267, p < 0.01). The inverse relationship of PFAS to the antioxidant protein α-klotho in those with healthy kidney function has not been previously reported and should be evaluated in other populations.