Soluble klotho as an effective biomarker to characterize inflammatory states

Abstract

Background & Aims Soluble α-Klotho (s-Klotho) is a circulating protein with pleiotropic effects that mainly induce protective effects. Our study investigates the associations between s-Klotho and several established inflammatory biomarkers, with the aim of examining whether s-Klotho levels are representative of inflammatory states. Methods A total of 11,128 eligible participants from NHANES 2007–2016 were included in our study. Levels of four inflammatory biomarkers, uric acid (UA), C-reactive protein (CRP), white blood cell (WBC) count, and mean platelet volume (MPV), were examined for their relationship with s-Klotho levels. Sub-analyses sorted the total population by gender and into four quartiles. Linear regression models were used to evaluate the strengths of associations. Results All four inflammatory biomarkers were significantly associated with s-Klotho levels. UA, CRP, and WBC count showed an inverse association, while MPV showed a direct one. Of the four markers, UA was most strongly correlated with s-Klotho levels (β coefficient: −28.89 in unadjusted model, p <.001), and this relationship was stronger in women than in men (β coefficient of UA in men: −22.01, p <.001; in women: −31.54, p <.001). In addition, all four biomarkers manifested stronger associations with s-Klotho in higher quartiles, and the highest absolute values of β coefficients appeared in Q4 vs. Q1. Conclusion s-Klotho is significantly associated with well-recognized inflammatory biomarkers. A decrease in s-Klotho levels implies a general inflammatory status; therefore, s-Klotho serves as a potential biomarker that is inversely correlated with inflammatory conditions. Further applications in clinical practice will provide us with a better understanding of its role. Key messages Soluble α-Klotho (s-Klotho) levels are significantly associated with the inflammatory markers uric acid, C-reactive protein, white blood cell count, and mean platelet volume. S-Klotho is involved in inflammatory processes and plays a protective role. S-Klotho may serve as an inverse indicator of inflammation.

Serum Levels of α-Klotho, Inflammation-Related Cytokines, and Mortality in Hemodialysis Patients

“…In the latest studies, soluble α-Klotho has been shown to be significantly associated with well-recognized inflammatory biomarkers, e.g., uric acid (UA) [ 30 , 31 ], C-reactive protein (CRP), white blood cell (WBC) count, and mean platelet volume (MPV) [ 31 ]. In PD patients, high concentrations of Klotho (above the median value of 329 pg/mL) were associated with lower IL-6 levels [ 17 ].…”

Composite Dietary Antioxidant Index and Plasma Levels of Soluble Klotho: Insights from NHANES

“…Martín-Núñez et al found that reduced levels of S-Klotho were associated with the proinflammatory status, such as higher ratio of tumor necrosis factor-alpha/interleukin-10 and the C-reactive protein level [ 27 ]. Wu et al also demonstrated that the serum levels of S-Klotho were significantly and inversely associated with four well-recognized inflammation-related biomarkers (white blood cell count, mean platelet volume, C-reactive protein, and uric acid) in the cohort [ 28 ]. Several experimental models demonstrated that upregulation of endogenous Klotho or exogenous administration of Klotho both could suppress renal fibrosis and maintain kidney function in chronic kidney disease [ 29 ].…”

Birth size and the pace of aging in men

“…However, it is also important to note that many studies show a positive correlation between s-Klotho and markers of health and biological age [128][129], also in patients with various disorders [130].…”