The impact of protein nutritional supplementation on erythropoietin resistance in hemodialysis patients with protein-energy wasting: a randomized clinical trial

Protein-energy wasting (PEW) is prevalent among hemodialysis patients and contributes to erythropoietin (EPO) resistance, which is associated with heightened anemia and cardiovascular risks. The present study sought to evaluate the impact of oral protein supplementation on EPO resistance among hemodialysis patients with PEW. This was an open-label, parallel-group, randomized clinical trial that was carried out in 2024 on 52 hemodialysis patients at Imam Hossein Hospital in Tehran, Iran. The subjects were randomly assigned to receive a dosage of an oral protein powder supplement (intervention group) or receive no intervention (control group) for a duration of four months. The outcomes consisted of the occurring changes in erythropoietin resistance, serum iron profiles, hemoglobin levels, and PEW, evaluated prior to and following the intervention using the Malnutrition Universal Screening Tool (MUST) scores, and body composition analysis conducted using the InBody S10 device. A significant improvement of nutritional status was observed in the intervention group compared to the control after four months (91.7% vs. 43.5% non-malnourished; P < 0.001). Although favorable trends were observed in the intervention group, experimental parameters, including erythropoietin resistance index, ferritin, transferrin saturation, and TIBC, showed no significant differences among the two study groups (P > 0.05). Body composition analysis revealed a considerable weight gain in the intervention group (+ 1.47 vs. − 0.45 kg; P = 0.040) and a significant decrease in ECW/TBW ratio (P = 0.003), whereas changes in body mass index, skeletal muscle mass, and protein content were negligible (P > 0.05). Oral protein supplementation improved the overall nutritional status and fluid balance in hemodialysis patients with PEW. While the definitive impact of oral protein supplementation on EOP resistance remains inconclusive, supplementation can be integrated into the nutritional management of malnourished hemodialysis patients.