Altered vascular function in chronic kidney disease: evidence from passive leg movement

Abstract

Chronic kidney disease (CKD) is an independent risk factor for the development of cardiovascular disease and is characterized by reduced nitric oxide (NO) bioavailability and vascular dysfunction, typically assessed using brachial artery flow-mediated dilation (FMD). It has been previously reported that passive leg movement (PLM)-induced hyperemia, an assessment of lower extremity vascular function, is highly dependent on NO, but has not yet been utilized to assess vascular function in patients with CKD. The purpose of this study was to comprehensively assess vascular function in patients with CKD using PLM, in addition to the traditional FMD technique. Assessment of vascular function via PLM and FMD was performed on 12 patients (CKD, 66 ± 3 years) and 16 age-matched healthy controls (CON, 60 ± 2 years). Blood velocity and artery diameters during PLM and FMD were measured using duplex ultrasound of the femoral and brachial arteries, respectively. Habitual physical activity, assessed by accelerometry, was performed in a subset of each group. CKD patients had reduced peak leg blood flow (LBF) (384 ± 39 vs. 569 ± 77 mL/min, P < 0.05) and change in LBF from baseline to peak (∆peakLBF) (143 ± 22 vs. 249 ± 34 mL/min, P < 0.05) during PLM compared to CON. Additionally, PLM responses were significantly associated with kidney function and physical activity levels. As anticipated, FMD was significantly attenuated in CKD patients (5.2 ± 1.1 vs. 8.8 ± 1.2%, P < 0.05). In conclusion, both upper and lower extremity measures of vascular function indicate impairment in CKD patients when compared to controls. PLM appears to be a novel and feasible approach to assessing lower extremity vascular function in CKD.

Keywords: CKD; PLM; endothelial function; flow-mediated dilation; nitric oxide.

Figure 1

Hyperemia induced by passive leg movement (PLM). Second‐by‐second average LBF responses during PLM for CKD patients and healthy controls (CON) (A). Note: Figure A illustrates general blood flow trends that occurred during PLM. As the analyses were performed on data from individuals who exhibited varying response kinetics, second‐by‐second averaging removes some of the information obtained in individual recordings. Therefore, mean values for peak LBF (B) and ∆peakLBF (C) achieved within each group are also illustrated separately. LBF, leg blood flow; ∆peakLBF, change in leg blood flow from baseline to peak; CON, healthy controls; CKD, chronic kidney disease; *P < 0.05.

Figure 2

Associations between renal function and hyperemia evoked by passive leg movement (PLM). Renal function as indicated by eGFR was significantly associated with peak LBF (A) and ∆peakLBF (B) achieved during PLM in all subjects (solid line). Correlations between PLM‐induced hyperemia and eGFR for only patients with CKD are also presented (dashed line). eGFR, estimated glomerular filtration rate; LBF, leg blood flow; ∆peakLBF, change in leg blood flow from baseline to peak; *P < 0.05.

Figure 3

Brachial artery responsiveness to flow‐mediated dilation (FMD). Brachial artery responsiveness, as quantified by the maximal percent change in diameter from baseline (%FMD) during the 2 min immediately following the release of cuff occlusion, was significantly reduced in CKD patients when compared to controls. CON, healthy controls; CKD, chronic kidney disease; *P < 0.05.

Figure 4

Associations between habitual physical activity and hyperemia evoked by passive leg movement (PLM). Habitual physical activity as expressed in average steps per day was significantly associated with both peak LBF (A) and ∆peakLBF (B) for all participants. Moderate‐to‐vigorous intensity physical activity (MVPA) as measured in minutes per week was also correlated with peak LBF (C) and ∆peakLBF (D). BF, leg blood flow; ∆peakLBF, change in leg blood flow from baseline to peak; CON, healthy controls; CKD, chronic kidney disease; *P < 0.05.

Figure 5

ADMA and MDA serum concentrations. ADMA concentrations were significantly higher in CKD patients when compared to controls (A). MDA concentrations were greater in CKD versus controls (B), however this difference was not statistically significant. ADMA, asymmetric dimethylarginine; MDA, malondialdehyde; CKD, chronic kidney disease, CON, healthy controls; *P < 0.05.