INTRODUCTION:
Chronic Kidney Disease (CKD) is characterized by a progressive decline in kidney function which has widespread effects on various organ systems including skeletal muscle. By the time renal replacement therapy is required, most patients have become so deconditioned that opportunities for exercise participation are very limited. Therefore, lifestyle interventions focused at maintaining or improving muscle health should be implemented at an earlier stage in the disease process. The present study compares the capacity of skeletal muscle tissue to respond to resistance exercise and protein supplementation between patients with CKD and healthy matched controls.
METHODS:
Twenty patients with advanced CKD but not on dialysis (stage G3b-G4, 3F/17M, age 66±13 y, BMI 30±5 kg/m2) and twenty sex-, age-, and BMI-matched controls (CON; 3F/17M, age 65±14 y, BMI 29±4 kg/m2) participated in this study. Baseline assessments included cardiopulmonary exercise testing, leg strength, and dual-energy x-ray absorptiometry. In a randomized cross-over design, participants followed their habitual lifestyle for 7 days and completed a 7-day intervention composed of 3 resistance exercise sessions with post-exercise ingestion of 20 g protein. To assess muscle protein synthesis rates, participants ingested deuterium oxide (2H2O) throughout the study period with blood and muscle samples being collected before (t=0) and after the first (t=7) and second week (t=14). Furthermore, mitochondrial respiration was assessed in muscle tissue obtained before and after the intervention. Cross-sectional and longitudinal data were compared using independent t-tests and two-way repeated measures ANOVA, respectively.
RESULTS:
Patients with advanced CKD were characterized by lower aerobic capacity compared with CON (21.3±5.9 vs 30.3±11.2 mL/kg/min, respectively; P=0.004), whereas lean mass (59±7 vs 61±11 kg, P=0.592) and leg strength (95±30 vs 106±44 kg, P=0.358) did not differ between groups. Maximal mitochondrial respiration was lower in patients with CKD compared with CON at baseline (376±71 vs 443±128 pmol/s/mg dry wt, respectively; P=0.048) and increased following the exercise intervention in both groups (408±94 vs 459±132 pmol/s/mg dry wt, respectively; P-time=0.025) with no differences in the responsiveness between groups (P-time*group=0.453). In line, habitual muscle protein synthesis rates were lower in CKD vs CON (1.13±0.23 vs 1.33±0.36 %/d, respectively; P=0.046) and were ~20% higher during the exercise intervention week in both groups (1.35±0.25 vs 1.60±0.39 %/d, respectively; P-time<0.001, P-time*group=0.675).
CONCLUSION:
Skeletal muscle in patients with CKD remains highly responsive to resistance exercise plus protein supplementation, with rapid increases in muscle protein synthesis rates and mitochondrial respiration. Exercise and nutritional prehabilitation seems warranted for CKD patients prior to the onset of renal replacement therapy.