Low sirtuin-1 levels are linked to erythropoietin resistance in hemodialysis patients

Abstract

Introduction Erythropoiesis-stimulating agents (ESAs) are widely used to manage anemia in chronic hemodialysis patients. However, some individuals exhibit ESA resistance, and its underlying mechanisms remain unclear. Sirtuin-1 (SIRT1), a key regulator of hypoxia and iron metabolism, may influence ESA responsiveness. This study investigates the relationship between SIRT1 levels and ESA resistance.Methods This cross-sectional study analyzed 391 chronic hemodialysis patients, including ESA-treated and untreated individuals. ESA responsiveness was assessed using the Erythropoietin Resistance Index (ERI), calculated as weekly body-weight-adjusted ESA dose divided by hemoglobin concentration. Associations between SIRT1 levels, ERI quartiles, and ESA responsiveness were examined.Results A total of 385 patients were included in the analysis. Serum SIRT1 levels were significantly lower in ESA-treated patients than in untreated individuals. A negative correlation was found between SIRT1 levels and ERI (r = −0.179, p < 0.001). Multiple regression analysis confirmed that both ERI (β = −0.158, p = 0.002) and ferritin levels (β = −0.121, p = 0.015) were independent negative predictors of SIRT1 (R2= 0.081). Patients with high ERI (≥50th percentile) had significantly lower SIRT1 levels. Logistic regression indicated that only SIRT1 was significantly associated with high ERI (B = −0.035, p = 0.018).Conclusion This study examined the relationship between SIRT1 levels and ESA hyporesponsiveness in patients undergoing hemodialysis. The findings demonstrate that lower SIRT1 levels are associated with higher ERI values, suggesting a potential role for SIRT1 in modulating ESA resistance.

Keywords

• Erythropoietin resistance
• sirtuin-1
• erythropoietin resistance index (ERI)
• HIF