Low Sirtuin-1 Levels Are Linked to Erythropoietin Resistance in Hemodialysis Patients.

This study explores the association between Sirtuin-1 (SIRT1) levels and erythropoietin resistance in hemodialysis patients. Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia in chronic kidney disease (CKD) patients undergoing hemodialysis. However, a significant proportion of patients exhibit hyporesponsiveness to ESAs, leading to suboptimal anemia management. SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase, regulates hypoxia and iron metabolism by modulating the activity of hypoxia-inducible factor 1α (HIF-1α). Lower SIRT1 levels may impair HIF-1α activity and contribute to reduced erythropoietin (EPO) responsiveness.

In this multicentric cross-sectional cohort study, 391 adult hemodialysis patients from provincial dialysis clinics in Bursa, Turkey, were enrolled between August 2020 and March 2021. ESA responsiveness was assessed using the Erythropoietin Resistance Index (ERI), calculated as the weekly weight-adjusted ESA dose divided by hemoglobin concentration. Serum SIRT1 levels were measured using a human SIRT1 ELISA kit.

The study aims to determine whether low SIRT1 levels are independently associated with higher ERI scores and to identify other clinical and biochemical parameters influencing ESA responsiveness. Multiple regression and correlation analyses will be performed to evaluate the relationship between SIRT1 levels, ERI scores, ferritin levels, and other clinical factors. Logistic regression will also be conducted to explore whether SIRT1 is an independent predictor of high ERI scores (≥50th percentile).

The findings from this study may provide new insights into the molecular mechanisms underlying ESA resistance and highlight the potential role of SIRT1 as a target for improving anemia management in hemodialysis patients.

Inclusion criteria

• Aged ≥18 years
• Receiving hemodialysis
• Availability of laboratory data to calculate ERI

Exclusion criteria

• Autosomal polycystic kidney disease
• Malignancies
• Infectious diseases
• Chronic rheumatological disorders
• Vitamin B12 or folic acid deficiency
• CRP levels ≥ 5 mg/L
• PTH levels ≥ 300 pg/dL
• Inadequate hemodialysis (Kt/Vurea < 1.2)