Association of Iron Deficiency and Erythropoiesis-Stimulating Agent Use with Anemia Outcomes in Progressive Chronic Kidney Disease

Background: Anemia is a common and clinically significant complication of progressive chronic kidney disease (CKD), primarily driven by impaired erythropoietin production and disturbances in iron homeostasis. Iron deficiency further exacerbates anemia and may influence the response to erythropoiesis‑stimulating agents (ESAs). The combined impact of iron status and ESA utilization on anemia outcomes in CKD patients in developing healthcare settings remains inadequately characterized. This study aimed to evaluate the association of iron deficiency and ESA therapy with anemia outcomes among patients with progressive CKD in tertiary care hospitals. Methodology: A multicenter retrospective analytical study was conducted at Rangers Hospital Lahore, Pakistan and Hamid Diagnostic Laboratory. Medical records of 312 patients diagnosed with stage 3–5 CKD between January 2025 and December 2025 were reviewed. Patients aged ≥18 years with documented hemoglobin, serum ferritin, and ESA treatment status were included. Iron deficiency was defined as ferritin <100 ng/mL. Primary outcomes included mean hemoglobin levels, prevalence of moderate‑to‑severe anemia, and hematologic response following treatment. Statistical analysis included chi‑square tests, independent t‑tests, and multivariable logistic regression to determine predictors of improved anemia outcomes. Results & Findings: Among the 312 CKD patients, 56.4% (n=176) were male and 43.6% (n=136) were female, with a mean age of 54.7 ± 13.2 years. Overall anemia prevalence was 82.1% (n=256), while iron deficiency was observed in 47.8% (n=149) of patients. ESA therapy was administered to 61.5% (n=192) of the cohort. Patients receiving ESAs with adequate iron stores demonstrated significantly higher mean hemoglobin levels (10.6 ± 1.2 g/dL) compared with those with iron deficiency receiving ESA therapy (9.3 ± 1.4 g/dL, p < 0.001). Multivariable regression analysis indicated that adequate iron status (OR = 2.41; 95% CI: 1.45–4.02, p = 0.001) and ESA therapy (OR = 1.88; 95% CI: 1.12–3.17, p = 0.017) were independently associated with improved anemia control. Conversely, advanced CKD stage (stage 5 vs. stage 3: OR = 0.48; 95% CI: 0.28–0.83, p = 0.008) and persistent iron deficiency were significant predictors of poor hematologic response. Conclusion: Iron deficiency remains highly prevalent among patients with progressive CKD and significantly limits the therapeutic effectiveness of ESA treatment. Optimal iron status substantially improves hemoglobin response and anemia outcomes in CKD populations. These findings highlight the importance of routine iron monitoring and integrated anemia management strategies to enhance treatment outcomes in CKD patients in resource‑limited tertiary care settings.