Decreased Circulating Klotho Levels in Patients Undergoing Dialysis and Relationship to Oxidative Stress and Inflammation

Abstract

Introduction It has been reported that klotho deficiency is associated with oxidative stress and inflammation in experimental kidney disease models. Patients with end-stage renal disease (ESRD) are particularly characterized by increased oxidative stress and inflammation. However, little is known about the relationship between these features and klotho in patients with ESRD. Methods We conducted a single-center, cross-sectional study of 78 patients receiving peritoneal dialysis (PD). Serum concentrations of klotho, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and 8-isoprostane were measured by enzyme-linked immunosorbent assay. To define factors independently associated with klotho, we determined Spearman's correlation coefficients for between co-variates and conducted multiple linear regression analyses. Results Patients were classified by median concentration of klotho. In patients with klotho levels > 329.6 pg/mL, serum 8-isoprostane and IL-6 levels were significantly higher than in those with klotho levels < 329.6 pg/mL. In correlation analyses, log 8-isoprostane (γ = -0.310, p = 0.006) and log IL-6 (γ = -0.343, p = 0.002) were inversely correlated with log klotho. After adjustment for age, gender, mean arterial pressure, log intact parathyroid hormone, and log IL-6, log 8-isoprostane was independently associated with log klotho (β = -0.158, p = 0.040). However, the significant relationship between klotho and IL-6 was not seen in an adjusted model. Conclusions This study showed that circulating klotho levels were significantly associated with 8-isoprostane levels in patients undergoing PD, suggesting a potential link between klotho deficiency and enhanced oxidative stress in ESRD patients.