Association of endothelial dysfunction and peripheral arterial disease with sarcopenia in chronic kidney disease

Background Endothelial dysfunction and peripheral arterial disease (PAD), which disturb skeletal muscle microperfusion, are highly prevalent in patients with chronic kidney disease (CKD). We evaluated the association of endothelial dysfunction and PAD with sarcopenia in patients with non-dialysis CKD. Methods This cross-sectional study included 420 patients with stages 3-5 non-dialysis CKD aged 69.0 +/- 11.8 years. Skeletal muscle index (skeletal muscle mass/height(2)), handgrip strength, 6-m gait speed and strength of hip flexion and knee extension were measured. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019. Endothelial dysfunction and PAD were assessed using the vascular reactivity index (VRI) and ankle-brachial index (ABI), respectively. A VRI < 1.0 was classified as poor endothelial function, and an ABI < 0.9 was defined as PAD. Additionally, endothelial and inflammatory biomarkers, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), asymmetric dimethylarginine, endothelin-1 (ET-1) and interleukin-6, were measured in a subgroup of 262 patients. Results Among the participants, 103 (24.5%) were classified as having sarcopenia. Compared with patients without sarcopenia, those with sarcopenia had significantly lower ABI (1.04 +/- 0.16 vs. 1.08 +/- 0.15, P = 0.028 for the right ABI; 1.01 +/- 0.16 vs. 1.06 +/- 0.16, P = 0.002 for the left ABI) and VRI (0.83 +/- 0.57 vs. 1.08 +/- 0.56, P < 0.001) and had higher serum levels of ICAM-1 (P < 0.001), VCAM-1 (P = 0.003) and ET-1 (P = 0.037). Multivariate logistic regression revealed that, beyond age and body mass index, the average ABI (odds ratio [OR]: 0.81/0.1 increase; 95% confidence interval [CI]: 0.67-0.98; P = 0.032) and VRI (OR: 0.93/0.1 increase; 95% CI: 0.88-0.98; P = 0.010) were independently associated with sarcopenia. Among the endothelial biomarkers measured, ICAM-1 (OR: 2.47/1-SD increase; 95% CI: 1.62-3.75) and VCAM-1 (OR: 1.91/1-SD increase; 95% CI: 1.27-2.87) were independent predictors of sarcopenia. Group stratification based on the cut-offs of VRI and ABI showed that those with both poor VRI and ABI had the greatest risk for sarcopenia (OR: 4.22; 95% CI: 1.69-10.49), compared with those with normal VRI and ABI. Conclusions Endothelial dysfunction and PAD are independently associated with sarcopenia in patients with stages 3-5 CKD, suggesting the dominant role of vascular dysfunction in sarcopenia.