Oral Nutritional Supplement Adherence and Nutritional Outcomes in Hemodialysis Patients—A Prospective Study

Background/Objectives: Protein-energy wasting (PEW) affects up to 75% of hemodialysis (HD) patients, yet adherence to oral nutritional supplements (ONSs) remains poorly understood. This study evaluated ONS adherence patterns, associated socio-demographic and psychological factors, and clinical outcomes over 24 months in chronic HD patients. Methods: A 24-month prospective study was conducted in 101 HD patients. Adherence was assessed using the 4-item Morisky Medication Adherence Scale (MMAS-4), and depressive symptoms with the Beck Depression Inventory (BDI). Nutritional status was evaluated using the Malnutrition–Inflammation Score (MIS) and anthropometric measurements. Laboratory markers were obtained. Individualized nutritional education was provided at each visit. Results: Regular ONS use was reported in 50.5% of patients. High adherence (MMAS-4 = 0) was observed in 36.6% of the cohort. Forgetfulness (45.3%) and adverse effects (34.4%) were the most common obstacles. Adherence was significantly associated with sex (p = 0.007), with men more frequently demonstrating low adherence. Education level showed a weak, but significant positive correlation with MMAS-4 score (Spearman’s ρ = 0.25, p = 0.018), indicating slightly lower adherence among more educated patients. MMAS-4 and BDI scores were positively correlated (Spearman’s ρ = 0.25, p = 0.04), indicating that greater depressive symptom burden was associated with lower adherence. Regular ONS users demonstrated improved nutritional status (lower MIS; 9 vs. 7, p < 0.001), higher hemoglobin (106 vs. 114 g/L, p = 0.03), and increased mid-upper arm circumference (MUAC; 26 vs. 28 cm, p = 0.02). Lean tissue mass was preserved over time (p = 0.009). However, individualized education had limited effect on patients with initially low adherence. Individualized nutritional education was associated with improved acceptance and implementation of recommendations. Over two years of follow-up, nutritional education was associated with preserved lean and fat tissue index (LTI, p = 0.009; FTI, p = 0.08), reductions in interdialytic weight gain, and significant improvements in MUAC, waist circumference, and scapular skinfold thickness (p = 0.03; p < 0.001; p = 0.02). Prealbumin and hemoglobin levels also increased significantly (p = 0.02; p = 0.04). However, education alone was insufficient for certain subgroups, particularly older patients and those initially classified as non-adherent. During follow-up, 17 patients died. Lower MUAC (OR = 2.97, 95% CI: 1.45–6.08) and triceps skinfold thickness (OR = 1.37, 95% CI: 1.12–1.68) were the strongest independent predictors of mortality. Conclusions: Adherence to ONSs remains suboptimal in HD patients. Individualized nutritional education was associated with improved adherence and nutritional status in some subgroups but may be insufficient in older or initially non-adherent patients. Simple anthropometric markers are strong mortality predictors and may offer practical value for routine monitoring.