BACKGROUND: Klotho is a kidney-derived protein that is involved in various kidney diseases. The role of serum soluble Klotho (sKlotho) in the anemia of patients undergoing hemodialysis has not been well characterized. OBJECTIVE: We aimed to characterize the relationship between sKlotho and hemoglobin (Hb) levels in this group of patients. DESIGN: A single-center cross-sectional study of 208 patients undergoing maintenance hemodialysis (MHD) and 50 healthy controls was performed between June 1 and 31, 2023. METHODS: Demographic information and biomedical parameters, such as age, body mass index, medication use, and their Hb, albumin, interleukin-6, and sKlotho concentrations, were obtained. Patients undergoing MHD were allocated to a group that achieved the Hb target (⩾110 g/L) and a group that did not (<
110 g/L). Correlation analysis and multivariate logistic and linear regression analyses were performed to evaluate the relationship of sKlotho with Hb concentration. RESULTS: Participants undergoing MHD had lower Hb and sKlotho concentrations than controls. Those who had not achieved the target Hb level were given fewer erythropoiesis-stimulating agents and had lower sKlotho and albumin concentrations, but higher interleukin-6 concentrations, than those who had achieved the Hb target. The sKlotho concentration positively correlated with the Hb concentration and was inversely associated with the incidence of a lack of achievement of the target Hb level. Multivariate logistic regression models revealed that there was a close association between sKlotho and a lack of achievement of the target Hb level after adjustment for potential confounders (odds ratio: 0.335, 95% confidence interval: 0.142-0.791, CONCLUSION: The circulating sKlotho concentration is very low, but deficiency of this protein is independently associated with a high risk of anemia in patients undergoing MHD. Therefore, the routine monitoring of sKlotho concentration might be useful in the management of renal anemia in such patients.