Background: Patients with CKD and diabetes are at higher risk of developing cardiovascular disease, in part, because of impaired endothelial function. Cardioprotective compounds such as resveratrol could improve endothelial function and attenuate the cardiovascular burden in patients with CKD and diabetes. We hypothesized that resveratrol supplementation would improve endothelial function in patients with CKD and diabetes. Methods: Twenty-eight adults aged 68±7 years (84% men) with stage 3 CKD and diabetes were enrolled in a randomized, double-blind, placebo-controlled, crossover study to investigate the effects of 6-week resveratrol supplementation (400 mg/d) on endothelial function. Endothelial function was determined through brachial artery flow-mediated dilation. Results: The mean values for eGFR and hemoglobin A_1c were 40±9 ml/min per 1.73 m² and 7.36%±0.72%, respectively. Compared with placebo, resveratrol supplementation increased flow-mediated dilation (ratio of geometric mean changes and 95% confidence interval for between-group comparisons, 1.43 (1.15 to 1.77); P value = 0.001). eGFR, hemoglobin A_1c, BP, and nitroglycerin-mediated dilation were unchanged with resveratrol or placebo (P = 0.15), suggesting the observed change in flow-mediated dilation was likely independent of changes in traditional cardiovascular risk factors. Conclusions: Resveratrol supplementation improved endothelial function in patients with CKD and diabetes. Clinical Trial registry name and registration number: Resveratrol and Vascular Function in CKD, NCT03597568. Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_11_20_CJN0000000000000337.mp3

Chronic kidney disease (CKD) increases the risk of cardiovascular disease and cognitive impairment. Curcumin is a polyphenol that improves vascular and cognitive function in older adults; however, its effects on vascular and cognitive function in patients with CKD are unknown. We hypothesized that curcumin supplementation would improve vascular and cognitive function in patients with CKD. Eighty-eight adults diagnosed with stage 3b or 4 CKD (aged 66 ± 8 years, 75% male) participated in a 12-month, randomized, double-blind, placebo-controlled study to test the effects of curcumin (Longvida^®, 2000 mg/day) on vascular and cognitive function. Our primary outcome was brachial artery flow-mediated dilation (FMD). Our secondary outcomes were nitroglycerin-mediated dilation, carotid–femoral pulse wave velocity (cfPWV), and cognitive function assessed via the NIH Toolbox Cognition Battery. At baseline, the mean estimated glomerular filtration rate was 34.7 ± 10.8, and the median albumin/creatinine ratio was 81.9 (9.7, 417.3). A total of 44% of participants had diabetes. Compared with placebo, 12 months of curcumin did not improve FMD (median change from baseline was −0.7 (−2.1, 1.1) and −0.1 (−1.5, 1.5) for curcumin and placebo, respectively, with p = 0.69). Similarly, there were no changes in nitroglycerin-mediated dilation, cfPWV, or cognitive outcomes. These results do not support chronic curcumin supplementation to improve vascular and cognitive function in patients with CKD.

Endothelial glycocalyx thickness and vascular endothelial function decline with advancing age. Endocalyx Pro is a glycocalyx-targeted therapy that may improve endothelial glycocalyx thickness and vascular endothelial function in older adults. This study demonstrated that 12-wk Endocalyx Pro supplementation did not improve overall endothelial glycocalyx thickness or flow-mediated dilation in older adults; however, Endocalyx Pro did increase capillary glycocalyx thickness in individuals not taking antihypertensive medication and improve flow-mediated dilation normalized to the shear stimulus.

The endothelial glycocalyx’s role in modulating vascular endothelial dysfunction with aging and disease is becoming increasingly recognized. This study presents novel findings that acute heparin administration is not a feasible method to experimentally degrade the endothelial glycocalyx and measure concurrent changes in vascular endothelial function in healthy humans. Alternative approaches will be needed to translate findings from preclinical studies and test the effects of acute endothelial glycocalyx degradation on vascular endothelial function in humans.

The novel finding is that load-dependent stiffness, not structural stiffness, is the primary mechanism of aortic stiffness, and is associated with reduced baroreflex sensitivity in women with a history of preeclampsia. These findings may help tailor high blood pressure prevention and management strategies in this population to prevent structural aortic stiffening, altered baroreflex control, and increased lifetime cardiovascular disease (CVD) risk.

Endothelial glycocalyx thickness declines with age, potentially increasing cardiovascular disease risk. However, sex differences in glycocalyx thickness and responses to glycocalyx‐targeted therapies remain unclear. This post hoc analysis examined sex differences in glycocalyx thickness and the effects of Endocalyx Pro supplementation in older adults. We analyzed data from 22 participants in a prior clinical trial (NCT06071728) that assessed 12‐week Endocalyx Pro (3712 mg/day) supplementation on vascular function. Glycocalyx thickness was estimated as the perfused boundary region (PBR) using the GlycoCheck, with higher PBR indicating smaller glycocalyx thickness. Postmenopausal females had higher PBR 4–25 than older males (2.11 ± 0.14 vs. 1.97 ± 0.13 μm; p = 0.02), particularly in microvessels 9–17 μm in diameter. Male sex (B [95% CI], −0.14 [−0.26, −0.02]; p = 0.02) and body mass index (BMI) (B [95% CI], −0.02 [−0.04, −0.01]; p = 0.01) were associated with lower PBR 4–25 in univariate analyses; however, when included in a multivariate model, the association with sex was attenuated (p = 0.15), while BMI remained significant (p = 0.04). After 12 weeks of Endocalyx Pro, PBR 4–25 increased in older males (+0.087 ± 0.148 μm) but decreased in postmenopausal females (−0.178 ± 0.148 μm; p = 0.009). In conclusion, we observed that postmenopausal females had smaller glycocalyx thickness, partially explained by BMI, and demonstrated a greater improvement with Endocalyx Pro, suggesting sex‐specific therapy effects.