Combined leucine supplementation and exercise to counteract sarcopenia in patients with end-stage kidney disease undergoing maintenance hemodialysis: a single-center randomized pilot study

Background: Sarcopenia affects approximately 30%-40% of patients with end-stage kidney disease (ESKD) undergoing maintenance hemodialysis (HD), a prevalence substantially higher than that observed in community-dwelling older adults. Muscle wasting in this population is driven by chronic inflammation, amino acid losses during dialysis, and anabolic resistance, which blunt muscle protein synthesis despite nutritional intake or exercise. Leucine, a branched-chain amino acid that activates mechanistic target of rapamycin complex 1 signaling, plays a key role in muscle anabolism but is often depleted in patients undergoing HD. This pilot study evaluated the feasibility and preliminary effects of combining leucine supplementation with exercise on muscle-related outcomes in ESKD patients. Methods: In this single-center randomized pilot trial, 24 patients undergoing maintenance HD were assigned to either exercise alone or exercise plus leucine supplementation for 12 weeks. The intervention group received 6 g/day of leucine in beverage and capsule form. The primary outcome was the change in handgrip strength. Secondary outcomes included physical performance measures (gait speed, five-times sit-to-stand, and Short Physical Performance Battery), skeletal muscle mass indices, body composition, and biochemical markers. Exploratory analyses included responder analysis and metabolomic correlation analysis in an independent cohort. Results: Baseline characteristics were generally comparable between groups. The intervention group showed higher responder rates for handgrip strength and gait speed compared with the exercise-only group, while modest increases in skeletal muscle index were observed only in the intervention group. Several biochemical markers, including total protein, blood urea nitrogen, creatinine, and red blood cell count, showed directional increases in the intervention group. Independent metabolomic profiling demonstrated lower circulating leucine levels and disrupted amino acid correlations in HD patients compared with healthy controls. Conclusion: Adjunct leucine supplementation combined with exercise showed preliminary improvements in muscle function and selected biochemical markers in patients with ESKD undergoing HD. These findings support the potential role of leucine-based nutritional strategies in mitigating sarcopenia in this population, although larger and longer-term trials are required to confirm efficacy.