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BackgroundThe anabolic response to progressive resistance exercise training (PRET) in haemodialysis patients is unclear. This pilot efficacy study aimed to determine whether high-intensity intradialytic PRET could reverse atrophy and consequently improve strength and physical function in haemodialysis patients. A second aim was to compare any anabolic response to that of healthy participants completing the same program.MethodsIn a single blind controlled study, 23 haemodialysis patients and 9 healthy individuals were randomly allocated to PRET or an attention control (SHAM) group. PRET completed high-intensity exercise leg extensions using novel equipment. SHAM completed low-intensity lower body stretching activities using ultra light resistance bands. Exercises were completed thrice weekly for 12 weeks, during dialysis in the haemodialysis patients. Outcomes included knee extensor muscle volume by magnetic resonance imaging, knee extensor strength by isometric dynamometer and lower body tests of physical function. Data were analysed by a per protocol method using between-group comparisons.ResultsPRET elicited a statistically and clinically significant anabolic response in haemodialysis patients (PRET—SHAM, mean difference [95 % CI]: 193[63 to 324] cm3) that was very similar to the response in healthy participants (PRET—SHAM, 169[−41 to 379] cm3). PRET increased strength in both haemodialysis patients and healthy participants. In contrast, PRET only enhanced lower body functional capacity in the healthy participants.ConclusionsIntradialytic PRET elicited a normal anabolic and strength response in haemodialysis patients. The lack of a change in functional capacity was surprising and warrants further investigation.

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Cardiovascular disease (CVD) is a major contributor to longterm mortality after liver transplantation (LT) necessitating aggressive modification of CVD risk. However, it is unclear how coronary artery disease (CAD) and the development of dyslipidemia following LT impacts clinical outcomes and how management of these factors may impact survival. Patients undergoing LT at Virginia Commonwealth University from January 2007 to January 2017 were included (n = 495). CAD and risk factors in all potential liver transplantation recipients (LTRs) over the age of 50 years were evaluated via coronary angiography. The impact of pre‐LT CAD after transplantation was evaluated via a survival analysis. Additionally, factors associated with new‐onset dyslipidemia, statin use, and mortality were assessed using multiple logistic regression or Cox proportional hazards models. The mean age of the cohort was 55.3 ± 9.3 years at the time of LT, and median follow‐up was 4.5 years. CAD was noted in 129 (26.1%) patients during the pre‐LT evaluation. The presence or severity of pre‐LT CAD did not impact post‐LT survival. Dyslipidemia was present in 96 patients at LT, and 157 patients developed new‐onset dyslipidemia after LT. Statins were underused as only 45.7% of patients with known CAD were on therapy. In patients with new‐onset dyslipidemia, statin therapy was initiated in 111 (71.1%), and median time to initiation of statin therapy was 2.5 years. Statin use conferred survival benefit (hazard ratio, 0.25; 95% confidence interval, 0.12‐0.49) and was well tolerated with only 12% of patients developing an adverse event requiring the cessation of therapy. In conclusion, pre‐LT CAD did not impact survival after LT, potentially suggesting a role of accelerated atherosclerosis that may not be captured on pre‐LT testing. Although statin therapy confers survival benefit, it is underused in LTRs.

Endothelial dysfunction and arterial stiffness are nontraditional risk factors of chronic kidney disease (CKD)-related cardiovascular disease (CVD) that could be targeted with exercise. This study investigated the effect of moderate to vigorous aerobic exercise on vascular function in nondialysis CKD. In this randomized, controlled trial, 36 nondialysis patients with CKD (means ± SE, age: 58 ± 2 yr, estimated glomerular filtration rate: 44 ± 2 ml·min−1·1.73 m−2) were allocated to an exercise training (EXT) or control (CON) arm. The EXT group performed 3 × 45 min of supervised exercise per week at 60–85% heart rate reserve for 12 wk, whereas the CON group received routine care. Outcomes were assessed at 0 and 12 wk. The primary outcome, microvascular function, was assessed via cutaneous vasodilation during local heating measured by laser-Doppler flowmetry coupled with microdialysis. Participants were instrumented with two microdialysis fibers for the delivery of 1) Ringer solution and 2) the superoxide scavenger tempol. Conduit artery function was assessed via brachial artery flow-mediated dilation. Aortic pressure waveforms and pulse wave velocity were acquired with tonometry and oscillometry. Microvascular function improved after EXT ( week 0 vs . week 12, EXT: 87 ± 2% vs. 91 ± 2% and CON: 86 ± 2% vs. 84 ± 3%, P = 0.03). At baseline, pharmacological delivery of tempol improved microvascular function (Ringer solution vs. tempol: 86 ± 1% vs. 90 ± 1%, P = 0.02) but was no longer effective after EXT (91 ± 2% vs. 87 ± 1%, P = 0.2), suggesting that an improved redox balance plays a role in EXT-related improvements. Brachial artery flow-mediated dilation was maintained after EXT (EXT: 2.6 ± 0.4% vs. 3.8 ± 0.8% and CON: 3.5 ± 0.6% vs. 2.3 ± 0.4%, P = 0.02). Central arterial hemodynamics and arterial stiffness were unchanged after EXT. Aerobic exercise improved microvascular function and maintained conduit artery function and should be considered as an adjunct therapy to reduce CVD risk in CKD.

This review discusses the associations of muscular strength (MusS) with cardiovascular disease (CVD), CVD-related death, and all-cause mortality, as well as CVD risk factors, such as metabolic syndrome, diabetes, obesity, and hypertension. We then briefly review the role of resistance exercise training in modulating CVD risk factors and incident CVD. The role of MusS has been investigated over the years, as it relates to the risk to develop CVD and CVD risk factors. Reduced MusS, also known as dynapenia, has been associated with increased risk for CVD, CVD-related mortality, and all-cause mortality. Moreover, reduced MusS is associated with increased cardiometabolic risk. The majority of the studies investigating the role of MusS with cardiometabolic risk, however, are observational studies, not allowing to ultimately determine association versus causation. Importantly, MusS is also essential for the identification of nutritional status and body composition abnormalities, such as frailty and sarcopenia, which are major risk factors for CVD.

Background/Aims: According to mathematical modeling, intradialytic exercise of sufficient intensity and duration implemented in the second half of dialysis should be as efficacious as increasing dialysis time for dialysis adequacy. This assumption has not been tested in vivo. Methods: In this controlled trial, 11 hemodialysis (HD) patients (mean (SD) age 56 (13) years) were recruited. Each patient completed three trial arms in a randomized order: routine care (CONT), increased HD time of 30 min (TIME), and intradialytic exercise (EXER), 60 min of cycling at 90% of the lactate threshold in the last 90 min of HD. The primary outcome was eKt/V_urea. Secondary outcomes included reduction and rebound ratios of urea, creatinine, phosphate and β₂-microglobulin.Outcomes were calculated from blood sampling collected pre-, post- and 30 min post-HD and confirmed with dialysate sampling. Results: Exercise was not as efficacious as increased HD time for eKt/V_urea (EXER vs. CONT, mean change (95% CI): 0.03 (-0.05 to 0.12); TIME vs. CONT: 0.15 (0.05-0.26)). Exercise was less efficacious at improving reduction ratios of urea and creatinine. However, exercise was more efficacious than increased dialysis time for phosphate reduction ratio (EXER vs. CONT: 8.6% (0.5-16.7); TIME vs. CONT: 5.0% (-1.0 to 11.1)). Conclusion: This study utilized a rigorously controlled in vivo design to test mathematical models and assumptions regarding dialysis adequacy. Intradialytic exercise towards the end of HD cannot replace the prescription of increased HD time for dialysis adequacy, but may be an adjunctive therapy for serum phosphate control.

Cardiovascular diseases (CVD) affect 1 in 3 adults and remain the leading causes of death in America. Advancing age is the major risk factor for CVD. Recent plateaus in CVD-related mortality rates in high income countries after decades of decline highlight a critical need to identify novel therapeutic targets and strategies to mitigate and manage the risk of CVD development and progression. Vascular dysfunction, characterized by endothelial dysfunction and large elastic artery stiffening, is independently associated with an increased CVD risk and incidence and is therefore an attractive target for CVD prevention and management. Vascular mitochondria have emerged as an important player in maintaining vascular homeostasis. As such, age and disease related impairments in mitochondrial function contribute to vascular dysfunction and consequent increases in CVD risk. This review outlines the role of mitochondria in vascular function and discusses the ramifications of mitochondrial dysfunction on vascular health in the setting of age and disease. The adverse vascular consequences of increased mitochondria derived reactive oxygen species, impaired mitochondrial quality control and defective mitochondrial calcium cycling are emphasized, in particular. Current evidence for both lifestyle and pharmaceutical mitochondrial-targeted strategies to improve vascular function is also presented.