Effects of long-term intradialytic oral nutrition and exercise on muscle protein homeostasis and markers of mitochondrial content in patients on hemodialysis

Patients with end-stage kidney disease on maintenance hemodialysis commonly develop protein-energy wasting, a syndrome characterized by nutritional and metabolic abnormalities. Nutritional supplementation and exercise are recommended to prevent protein-energy wasting. In a 6-mo prospective randomized, open-label, clinical trial, we reported that the combination of resistance exercise and nutritional supplementation does not have an additive effect on lean body mass measured by dual-energy X-ray absorptiometry. To provide more mechanistic data, we performed a secondary analysis where we hypothesized that the combination of nutritional supplementation and resistance exercise would have additive effects on muscle protein accretion by stable isotope protein kinetic experiments, muscle mass by MRI, and mitochondrial content markers in muscle. We found that 6 mo of nutritional supplementation during hemodialysis increased muscle protein net balance [baseline: 2.5 (-17.8, 13.0) mu g.100 mL(-1).min(-1) vs. 6 mo: 43.7 (13.0, 98.5) mu g.100 mL(-1).min(-1), median (interquartile range), P = 0.04] and mid-thigh fat area [baseline: 162.3 (104.7, 226.6) cm(2) vs. 6 mo: 181.9 (126.3, 279.2) cm(2), median (interquartile range), P = 0.04]. Three months of nutritional supplementation also increased markers of mitochondrial content in muscle. Although the study is underpowered to detected differences, the combination of nutritional supplementation and exercise failed to show further benefit in protein accretion or muscle cross-sectional area. We conclude that long-term nutritional supplementation increases the skeletal muscle anabolic effect, the fat cross-sectional area of the thigh, and markers of mitochondrial content in skeletal muscle.