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.

Cardiovascular disease is the leading cause of mortality in chronic kidney disease (CKD). Mitochondrial dysfunction secondary to CKD is a potential source of oxidative stress that may impair vascular function. This study sought to determine if mitochondria-derived reactive oxygen species contribute to microvascular dysfunction in stage 3-5 CKD. Cutaneous vasodilation in response to local heating was assessed in 20 CKD patients [60 ± 13 yr; estimated glomerular filtration rate (eGFR) 46 ± 13 ml·kg·1.73 m] and 11 matched healthy participants (58 ± 2 yr; eGFR >90 ml·kg·1.73 m). Participants were instrumented with two microdialysis fibers for the delivery of 1) Ringer solution, and 2) the mitochondria- specific superoxide scavenger MitoTempo. Skin blood flow was measured via laser Doppler flowmetry during standardized local heating (42°C). Cutaneous vascular conductance (CVC) was calculated as a percentage of the maximum conductance achieved with sodium nitroprusside infusion at 43°C. Urinary isofuran/F-isoprostane ratios were assessed by gas-chromatography mass spectroscopy. Isofuran-to-F-isoprostane ratios were increased in CKD patients (3.08 ± 0.32 vs. 1.69 ± 0.12 arbitrary units; P < 0.01) indicative of mitochondria-derived oxidative stress. Cutaneous vasodilation was impaired in CKD compared with healthy controls (87 ± 1 vs. 92 ± 1%CVC; P < 0.01). Infusion of MitoTempo significantly increased the plateau phase CVC in CKD patients (CKD Ringer vs. CKD MitoTempo: 87 ± 1 vs. 93 ± 1%CVC; P < 0.01) to similar levels observed in healthy controls ( P = 0.9). These data provide in vivo evidence that mitochondria-derived reactive oxygen species contribute to microvascular dysfunction in CKD and suggest that mitochondrial dysfunction may be a potential therapeutic target to improve CKD-related vascular dysfunction.

Background Reductions in exercise capacity associated with exercise intolerance augment cardiovascular disease risk and predict mortality in chronic kidney disease. This study utilized cardiopulmonary exercise testing to (a) investigate mechanisms of exercise intolerance; (b) unmask subclinical abnormalities that may precede cardiovascular disease in chronic kidney disease. Design The design of this study was cross-sectional. Methods Cardiopulmonary exercise testing was carried out in 31 Stage 3-4 chronic kidney disease patients (60 ± 11 years; estimated glomerular filtration rate 43 ± 13 ml/min/1.73 m) and 21 matched healthy individuals (healthy controls; 56 ± 5 years; estimated glomerular filtration rate>90 ml/min/1.73 m) on a cycle ergometer with workload increased by 15 W every minute until volitional fatigue. Breath-by-breath respiratory gas analysis was performed with an automated gas analyzer and averaged over 10 s intervals. Results Peak oxygen uptake was reduced in chronic kidney disease compared to healthy controls (17.43 ± 1.03 vs 28 ± 2.05 ml/kg/min; p < 0.01), as was oxygen uptake at the ventilatory threshold (9.44 ± 0.53 vs15.55 ± 1.34 ml/kg/min; p < 0.01). A steeper minute ventilation rate/carbon dioxide production slope (32 ± 0.8 vs 28 ± 1; p < 0.01) and a lower expired carbon dioxide pressure in chronic kidney disease (27 ± 0.6 vs 31 ± 0.9 vs 0.9; p < 0.01) indicated ventilation perfusion mismatching in these patients. The ventilatory cost of oxygen uptake was higher in chronic kidney disease (37 ± 0.8 vs 33 ± 1; p < 0.01). Maximum heart rate (134 ± 5 vs 159 ± 3 bpm) and one-minute heart rate recovery (15 ± 1 vs 20 ± 2 bpm) were reduced in chronic kidney disease ( p < 0.01). Conclusion This study suggests that both central and peripheral limitations likely contribute to reduced exercise capacity in non-dialysis chronic kidney disease. Additionally, cardiopulmonary exercise testing revealed subclinical cardiopulmonary abnormalities in these patients in the absence of overt cardiovascular disease. Cardiopulmonary exercise testing could potentially be a tool for unmasking cardiopulmonary abnormalities preceding cardiovascular disease in chronic kidney disease.

High dietary sodium intake can lead to hypertension and increased incidence of cardiovascular disease. We sought to determine the effect of short-term dietary sodium loading on central blood pressure and arterial stiffness in young (YG; 22–40 years) and middle-aged (MA; 41–60 years) normotensive adults. YG (n=49; age: 27±1 yrs) and MA (n=36; age: 52±1 yrs) subjects were randomized, in a cross-over design, to 7 days of low sodium (20mmol/day) or high sodium (300mmol/day) diet. On the last day of each diet, central pressures, forward and reflected wave amplitudes (via radial artery applanation tonometry) and carotid-femoral pulse wave velocity (CF-PWV) were assessed. Central systolic blood pressure (cSBP) was greater after HS in both YG (LS: 96±1 vs. HS: 99±1mmHg; p=0.012) and MA (LS: 106±2 vs. HS: 115±3mmHg; p<0.001). However, the increase in cSBP was greater in MA (YG: 4±1 vs. MA: 9±2; p=0.02). In MA subjects, HS elicited greater forward (LS: 25±1 vs. HS: 29±1mmHg; p<0.001) and reflected (LS: 19±1 vs. HS: 23±1mmHg; p<0.001) wave amplitudes. CF-PWV was also greater in MA on HS but after adjustment for MAP the difference was no longer significant. Our data indicate that HS intake leads to a greater increase in cSBP in MA adults, which may be the result of increased forward and reflected wave amplitudes.

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