The effect of exercise on vascular health in chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials

Abstract

Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease. This increased risk cannot be fully explained by traditional risk factors such as hypertension. Endothelial dysfunction and arterial stiffness have been suggested as factors that explain some of the increased risk and are independently associated with important cardiovascular outcomes in patients with CKD. Studies in other disease populations have shown the positive effects of exercise on vascular dysfunction. The aim of this review was to determine whether exercise training interventions improve measures of vascular function and morphology in patients across the spectrum of CKD and which exercise training interventions are most efficacious. A systematic search of Medline, Embase, and the Cochrane Central Register identified 25 randomized controlled trials. Only randomized control trials using an exercise intervention with a nonexercising control group and at least one measure of vascular function or morphology were included. Participants were patients with nondialysis CKD or transplant patients or those requiring dialysis therapy. A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A meta-analysis was completed for pulse wave velocity, augmentation index, and measures of endothelium-dependent vasodilation. Data from 25 studies with 872 participants showed that exercise training reduced pulse wave velocity and augmentation index but had no effect on endothelium-dependent vasodilation. Subgroup analyses suggested that exercise interventions of at least moderate intensity were more likely to be effective. Limitations included the absence of observational studies or other interventions aimed at increasing habitual physical activity. Further studies are warranted to investigate which are the most effective exercise interventions.NEW & NOTEWORTHY A thorough systematic review and meta-analysis of the effects of exercise training on measures of vascular function in patients with chronic kidney disease, including arterial stiffness and endothelial function, were conducted. Subgroup analyses investigated how differences in exercise training, according to frequency, intensity, type, and timing, have an impact on the efficacy of the intervention.

Keywords: arterial stiffness; chronic kidney disease; endothelial; exercise.

Graphical abstract

Figure 1.

PRISMA 2020-compliant flow diagram using the PRISMA2020 R package (64). Automation tools were used to remove non-English language studies and conference abstracts in the Embase search. In reasons for exclusion, “Comparator” includes single-arm studies without a comparator as well as studies with an inappropriate comparator (e.g., comparator did not receive dietary intervention when the intervention arm did), and “Other” includes one article that was a protocol only, a review article, and a study that was an extended followup of an included study. Some studies may have had multiple reasons for exclusion; the reason recorded is in the order of participant, intervention, comparison, outcomes, and study design (PICOS). PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Figure 2.

RoB2 traffic light plot for the risk of bias of all included studies. This was produced using the R package robvis (90).

Figure 3.

Forest plots of the effect estimates [mean difference (MD)] with 95% confidence intervals (CI) for pulse wave velocity (in m/s) between exercise interventions and control groups for all included studies, with subgroup analysis of the chronic kidney disease (CKD) population. cf-PWV, carotid-femoral PWV; HD, hemodialysis; PD, peritoneal dialysis; I², estimate of the proportion of observed variance that is due to real differences in effect size; τ, estimate of the SD of the true effect size.

Figure 4.

Forest plots of the effect estimates [mean difference (MD)] with 95% confidence intervals (CI) for the augmentation index (in %) between exercise interventions and control groups for all included studies, with subgroup analysis of the chronic kidney disease (CKD) population. HD, hemodialysis; I², estimate of the proportion of observed variance that is due to real differences in effect size; τ, estimate of the SD of the true effect size.

Figure 5.

Forest plots of effect estimates [standardized mean difference (SMD)] with 95% confidence intervals (CI) for endothelial function measures between exercise interventions and control groups for all included studies [flow-mediated dilation (FMD) and reactive hyperemia index (RHI) as measured by peripheral arterial tonometry]. All results are end of trial means, not changes from baseline. I², estimate of the proportion of observed variance that is due to real differences in effect size; τ, estimate of the SD of the true effect size.

Figure 6.

Funnel plot of the mean difference in pulse wave velocity (PWV) among patients with chronic kidney disease after exercise training interventions compared with control. Individual mean differences (in m/s) in PWV in each study are plotted against a measure of each study’s precision (the SE of the mean difference); any asymmetry in the plot indicates the degree of publication bias in the effect estimates. cf-PWV, carotid-femoral PWV.

Figure 7.

Funnel plot of the mean difference in augmentation index among patients with chronic kidney disease after exercise training interventions compared with control. Individual mean differences (in %) in the augmentation index in each study are plotted against a measure of each study’s precision (the SE of the mean difference); any asymmetry in the plot indicates the degree of publication bias in the effect estimates.