AGEs accumulation is related to muscle degeneration and vascular calcification in peritoneal dialysis patients

Abstract Background: Patients with chronic kidney disease (CKD) are affected by dynapenia, sarcopenia, and vascular calcification. Advanced glycation end products (AGEs) may accumulate in peritoneal dialysis (PD) patients and favor sarcopenia via changes in collagen cross-linking, muscle protein breakdown, and the calcification of arterial smooth muscle cells via p38-MAPK activation. The aim of this study is to explore the relationships between AGEs, muscle degeneration, and coronary artery calcification. Methods: This was a clinical observational study in patients with CKD undergoing PD, in which serum and skin AGEs (AGEs-sAF), cumulative glucose load, muscle strength and functional tests, muscle ultrasounds with elastography, coronary artery calcium (CAC) quantification, and muscle density by multislice computed tomography were measured. Results: 27 patients aged 48±16 years, dialysis vintage of 27±17 months, had AGEs-sAF levels of 3.09±0.65 AU (elevated in 13 [87%] patients), grip strength levels of 26.2±9.2 kg (11 [42%] patients with dynapenia), gait speed of 1.04±0.3 m/s (abnormal in 14 [58%] patients) and "timed-up-and-go test" (TUG) of 10.5±2.2s (abnormal in 7 [26%] patients). Correlations between AGEs-sAF levels and femoral rectus elastography (R=-0.74; p=0.02), anterior-tibialis elastography (R= -0.68; p=0.04) and CAC (R=0.64; p=0.04) were detected. Cumulative glucose load correlated with femoral rectal elastography (R=-0.6; p=0.02), and serum glycated hemoglobin concentrations correlated with psoas muscle density (R= -0.58; p=0.04) and CAC correlated with psoas muscle density (R=0.57; p=0.01) and lumbar square muscle density (R=-0.63; p=0.005). Conclusions: The study revealed associations between AGEs accumulation and lower muscle stiffness/density. Associations that linked muscle degeneration parameters with vascular calcification were observed.

摘要 背景：慢性肾脏病（CKD）患者常合并肌力减少、肌少症及血管钙化。晚期糖基化终末产物（AGEs）可在腹膜透析（PD）患者体内蓄积，通过胶原交联改变、肌肉蛋白分解以及经p38丝裂原活化蛋白激酶（p38-MAPK）激活诱导动脉平滑肌细胞钙化，进而促进肌少症发生。本研究旨在探讨晚期糖基化终末产物、肌肉退变与冠状动脉钙化之间的关联。
方法：本研究为针对接受腹膜透析的慢性肾脏病患者的临床观察性研究，检测了受试者血清及皮肤晚期糖基化终末产物-皮肤自体荧光（AGEs-sAF）、累计糖负荷、肌肉力量与功能指标、弹性成像超声肌肉检查结果、冠状动脉钙化（CAC）定量结果，以及通过多层计算机断层扫描获取的肌肉密度数据。
结果：本研究共纳入27例患者，年龄为48±16岁，透析时长为27±17个月；其AGEs-sAF水平为3.09±0.65任意单位（AU），其中13例（87%）患者水平升高；握力为26.2±9.2kg，11例（42%）患者存在肌力减少；步速为1.04±0.3m/s，14例（58%）患者步速异常；“计时起立行走测试（TUG）”时长为10.5±2.2s，7例（26%）患者测试结果异常。研究检测到AGEs-sAF水平与股直肌弹性成像（R=-0.74；P=0.02）、胫骨前肌弹性成像（R=-0.68；P=0.04）及冠状动脉钙化（R=0.64；P=0.04）存在相关性。累计糖负荷与股直肌弹性成像（R=-0.6；P=0.02）相关；血清糖化血红蛋白浓度与腰大肌密度（R=-0.58；P=0.04）相关；冠状动脉钙化与腰大肌密度（R=0.57；P=0.01）及腰方肌密度（R=-0.63；P=0.005）相关。
结论：本研究揭示了晚期糖基化终末产物蓄积与肌肉硬度/密度降低之间存在关联，同时观察到肌肉退变相关参数与血管钙化之间存在相关性。