Abstract

Introduction: Increased susceptibility of endothelial dysfunction and skeletal muscle impairments suggest peripheral limitations as an explanation for diminished aerobic capacity in chronic kidney disease (CKD) patients. However, data on peripheral limitations in CKD patients is limited. Hypothesis: We hypothesized CKD patients would experience reduced muscle oxygenation responses to acute exercise and cellular evidence of declines in vascular health compared to those without CKD. Methods: Sixteen male Veterans (CKD: n=9, age 74±6 yrs, eGFR, 41.7±10 mL/min/1.73 m 2 ; non-CKD controls (CON): n=7, age, 67±8 yrs, eGFR, 75±10.6 mL/min/1.73 m 2 ) completed treadmill cardiopulmonary exercise testing via the Modified Bruce protocol. Oxygenation responses were obtained from the medial gastrocnemius using near-infrared spectroscopy. Blood samples were collected at rest and analyzed for colony-forming units (CFU), flow-cytometry of mononuclear cells (MNCs) focusing on endothelial lineage cells and gene expression of MNCs. Effect sizes between groups were determined using Hedge’s g (g). Results: At peak exercise, oxygen consumption (VO 2peak 19±5 vs 25.8±5.2 ml/kg/min -1 , g=1.2), heart rate (HR peak 132±21 vs 160±9 bpm, g=1.6), oxygen extraction (Δ[HHb] 14.8±10.8 vs 24.9±6.8 a.u., g=1.0), and change in total hemoglobin concentration (Δ[tHb] 8.9±5.1 vs 22.5±12.8 a.u., g=1.4) were lower in CKD compared to CON. At an exercise intensity of 3.4 METs, Δ[HHb] and Δ[tHb] were 42% and 54% lower (8.0±7.8 vs 13.8±8.8 a.u., g=0.6 and 4.9±4.1 vs 10.7±4.5 a.u., g=1.2) in CKD vs CON, despite no differences in oxygen consumption or heart rate. CD34 + 184 expression was 47% lower in CKD vs CON (0.2±0.04 vs 0.38±0.48 %, g=0.5). CFU was significantly inversely correlated with body mass index and waist circumference (r=-0.67, p=0.034; r=-0.65, p=0.041). Conclusions: Preliminary data from this ongoing study suggest oxygen extraction and capillary blood volume expansion are impaired during exercise in CKD patients when compared to those without CKD. CD34 + 184 expression was lower in CKD patients versus those without CKD, indicating poor hematopoietic stem cell migratory function in the CKD group. In addition, an inverse association between CFU and body habitus was observed.

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