Sex-specific effects of mild kidney dysfunction on vascular function in midlife and older adults

Mild kidney dysfunction (MKD) increases cardiovascular disease (CVD) risk. Vascular dysfunction, including vascular endothelial dysfunction and aortic stiffening, is a key antecedent to CVD, but the impact of MKD on vascular function in midlife/older (ML/O) adults is not established. Moreover, sex is a biological variable that influences vascular function, but whether sex modulates the effects of MKD on vascular function is unclear. Vascular endothelial function (brachial artery flow-mediated dilation, FMD_BA) and aortic stiffness (carotid-femoral pulse wave velocity, PWV_CF) were compared in 93 ML/O men and postmenopausal women with MKD [estimated glomerular filtration rate (eGFR): 60-89 mL/min/1.73 m²] versus 78 ML/O adults without MKD (healthy controls; eGFR: ≥90 mL/min/1.73 m²) (age: 50+ yr). Circulating markers of inflammation and oxidative stress were also assessed. FMD_BA was lower in men with MKD (4.0 ± 0.3%) versus healthy controls (5.5 ± 0.5%; P = 0.0097) and correlated with eGFR (r_s = 0.30, P = 0.0073). There was no difference in FMD_BA between women with MKD (4.7 ± 0.4%) and healthy controls (4.8 ± 0.5%; P = 0.86) and no relation with eGFR. PWV_CF was higher in men with MKD (9.4 ± 0.2 m/s) versus controls (8.4 ± 0.3 m/s; P = 0.030) and correlated with eGFR (r = -0.34, P = 0.0013). However, PWV_CF was not different between women with MKD (9.3 ± 0.5 m/s) and controls (10.1 ± 0.4 m/s; P = 0.099) and not related to eGFR. The observed effects of MKD on vascular function were independent of traditional CVD risk factors and medication use. There were no differences in markers of inflammation nor oxidative stress between controls and MKD. Our findings suggest that vascular dysfunction may contribute to increased CVD risk associated with MKD in ML/O men but not in postmenopausal women.NEW & NOTEWORTHY Midlife/older (ML/O) adults with mild kidney dysfunction (MKD) are at an increased CVD risk compared with ML/O adults with normal kidney function. We assessed whether ML/O men and postmenopausal women with MKD exhibit vascular dysfunction compared with ML/O adults without MKD. We observed MKD-related vascular dysfunction in men but not in women. Thus, vascular dysfunction may contribute to MKD-associated increases in CVD risk in men but is unlikely to contribute to the increased risk in postmenopausal women.