Relationship of sKlotho with hemoglobin level in patients undergoing maintenance hemodialysis: a case-control study

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.

We aimed to characterize the relationship between sKlotho and hemoglobin (Hb) levels in this group of patients.

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.

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.

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, p = 0.013). This relationship was closer on multivariate linear regression analysis when sKlotho was included as a continuous variable.

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.