Effects of Nutritional Supplementation Combined with Exercise Training on Frailty, Physical Function, and Quality of Life in Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Objective: A combined intervention strategy of nutritional supplementation and exercise training has the potential to support the treatment of frailty and improve health outcomes in patients with chronic kidney disease (CKD). This study aimed to evaluate the effectiveness of nutritional supplementation combined with an exercise training intervention on frailty characteristics, physical function, and health-related quality of life in patients with CKD.

Design And Methods: PubMed, Embase, Web of Science, and Scopus were searched from inception to October 22, 2022, and the search was updated in May 2023. A randomized controlled trial (RCT) compared nutritional supplementation combined with exercise training to usual care/single nutritional supplementation or exercise training to assess the effect on Fried-based frailty characteristics and physical function in CKD patients was included. Two authors independently selected literature, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool 2. The outcome was analyzed using a random-effect model using the Hartung-Knapp-Sidik-Jonkman method or a fixed-effect model using restricted maximum likelihood. Using the "leave-one-out" method for sensitivity analysis.

Results: Seven articles (nine trials with a total of 324 patients) were included. Meta-analysis showed that nutritional supplementation combined with an exercise training intervention may improve frailty characteristics of dialysis patients, such as walking speed (mean difference (MD): 0.09 m/s, 95% (confidence interval) CI 0.02 to 0.16), and physical functioning, such as cardiorespiratory fitness (standardized mean difference (SMD): 0.56, 95% CI 0.20 to 0.93), and lower extremity mobility as assessed by the timed up and go test (MD: -1.11 s, 95% CI -1.79 to -0.43). However, the effect of combined interventions on other indicators such as body weight (MD: 1.28 kg, 95% CI -2.06 to 4.62), fatigue (SMD: 0.57, 95% CI -1.44 to 0.30), and health-related quality of life is uncertain. These results should be interpreted with caution because of the heterogeneity of the included studies and the relatively small sample size.

Conclusion: An intervention strategy of nutritional supplementation combined with exercise training may help improve frailty and physical functioning in CKD patients, particularly walking speed, cardiorespiratory fitness, and lower extremity mobility. Future studies should focus on larger sample sizes and longer-term follow-up to confirm these preliminary findings and explore potential effects on other health indicators.