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

Abstract

It has been hypothesized that α-Klotho deficiency might contribute to chronic inflammation in patients with end-stage renal disease (ESRD), especially those on hemodialysis (HD). Serum Klotho levels by some authors are considered a potential predictor of cerebrovascular events. Therefore, we analyzed serum levels of α-Klotho with ELISA and inflammation-related cytokines in HD patients. Sixty-seven HD patients and 19 healthy people were recruited between November 2017 and June 2021. A Cytometric Bead Array (CBA) was used to determine the level of different cytokines: IL-12p70, TNF, IL-10, IL-6, IL-1β, and IL-8. A human Klotho ELISA kit was used to determine the level of α-Klotho in the plasma samples of HD patients. There was no difference in serum levels of α-Klotho between HD patients and healthy people. Patients had increased serum IL-6 and IL-8. Significant positive correlations existed between the concentration of α-Klotho and the serum concentrations of IL-12p70, IL-10, and IL-1β. However, in a multivariable linear regression analysis, only patients’ age was associated independently with α-Klotho level. Serum α-Klotho was not associated with higher mortality risk in HD patients. While these results draw attention to potential relationships between α-Klotho proteins and inflammatory markers in HD patients, our cross-sectional study could not confirm the pathogenic link between α-Klotho, inflammation, and cardiovascular mortality.

Novel Biomarkers in Evaluating Cardiac Function in Patients on Hemodialysis—A Pilot Prospective Observational Cohort Study

“…These differences are most likely due to a lower inflammation status in our cohort (CRP 0.43 mg/dL vs./8.46 mg/dL in Yu cohort) [ 37 ]. In addition, in another recently published study by Lisowska on 67 HD patients, the mean IL-1B levels were 1.75 pg/mL, much lower than Yu’s results and lower than the values from our cohort [ 38 ]. These differences may be in the context of several factors: inflammation and nutrition status, hemoglobin levels and anemia management, dialysis vintage, comorbidities and the number of patients.…”

Association between Serum Soluble α-Klotho and Urinary Albumin Excretion in Middle-Aged and Older US Adults: NHANES 2007–2016

“…In summary, the complex pathophysiologic mechanisms suggested that Klotho downregulation is not merely an early biomarker for kidney damage, but also one of the principal complications of CKD and may play a pathogenic role in CKD progression [ 24 ]. Additionally, due to the complexity of the mechanism, whether serum Klotho reflects kidney function remains controversial in some studies [ 49 , 50 ], which requires high-quality research evidence.…”

Relationship between plasma atherogenic index of plasma (AIP) and Klotho protein: A cross-sectional study

“…Further research has revealed that Klotho protein plays a crucial role in physiological and pathological processes such as cell apoptosis, cell proliferation, antioxidant defense, and in ammatory response. Speci cally, in the occurrence and development of atherosclerosis, Klotho protein may exert important protective effects through reducing oxidative stress, suppressing in ammatory response, and regulating lipid metabolism, among other pathways [11][12][13].…”