Asad Halah Nori, Al-Hakeim Hussein Kadhem, Moustafa Shatha Rouf, Maes Michael
Al Najaf Health Directorate, Higher Health Institute, Najaf, Iraq.
Department of Chemistry, College of Science, University of Kufa, Iraq.
CNS Neurol Disord Drug Targets. 2023;22(2):191-206. doi: 10.2174/1871527321666220401140747.
End-stage renal disease (ESRD) is associated with fatigue and physiosomatic symptoms.
The objective of this study is to delineate the associations between severity of fatigue and physio-somatic symptoms and glomerular filtration rate, inflammatory biomarkers, and Wnt/cateninpathway proteins.
The Wnt-pathway related proteins β-catenin, Dickkopf-related protein 1 (DKK1), R-spondin- 1, and sclerostin were measured by ELISA technique in 60 ESRD patients and 30 controls. The Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale was used to assess the severity of FF symptoms.
ESRD is characterized by a significant increase in the total FF score, muscle tension, fatigue, sadness, sleep disorders, gastro-intestinal (GI) symptoms, and a flu-like malaise. The total-FF score was significantly correlated with serum levels of urea, creatinine, and copper (positively), and β-catenin, eGFR, hemoglobin, albumin, and zinc (inversely). The total-FF score was associated with the number of total dialysis and weekly dialysis sessions, and these dialysis characteristics were more important in predicting FF scores than eGFR measurements. Partial Least Squares analysis showed that the FF score comprised two factors that are differently associated with biomarkers: a) 43.0% of the variance in fatigue, GI symptoms, muscle tension, sadness, and insomnia is explained by hemoglobin, albumin, zinc, β-catenin, and R-spondin-1; and b) 22.3% of the variance in irritability, concentration and memory impairments by increased copper and cations/chloride ratio, and male sex.
ESRD patients show high levels of fatigue and physio-somatic symptoms associated with hemodialysis and mediated by dialysis-induced changes in inflammatory pathways, the Wnt/catenin pathway, and copper.
终末期肾病（ESRD）与疲劳及身心症状相关。
本研究旨在描述疲劳和身心症状的严重程度与肾小球滤过率、炎症生物标志物及Wnt/连环蛋白信号通路蛋白之间的关联。
采用酶联免疫吸附测定（ELISA）技术，对60例ESRD患者和30例对照者检测Wnt信号通路相关蛋白β-连环蛋白、Dickkopf相关蛋白1（DKK1）、R-spondin-1和硬化蛋白。使用纤维肌痛和慢性疲劳综合征（FF）评定量表评估FF症状的严重程度。
ESRD的特征为FF总分、肌肉紧张、疲劳、悲伤、睡眠障碍、胃肠道（GI）症状及类流感不适显著增加。FF总分与血清尿素、肌酐和铜水平（正相关），以及β-连环蛋白、估算肾小球滤过率（eGFR）、血红蛋白、白蛋白和锌水平（负相关）显著相关。FF总分与总透析次数和每周透析次数相关联，且这些透析特征在预测FF评分方面比eGFR测量更为重要。偏最小二乘法分析显示，FF评分包含两个与生物标志物关联不同的因素：a）血红蛋白、白蛋白、锌、β-连环蛋白和R-spondin-1可解释疲劳、GI症状、肌肉紧张、悲伤和失眠方面43.0%的变异；b）铜和阳离子/氯离子比值升高及男性性别可解释易怒、注意力和记忆力损害方面22.3%的变异。
ESRD患者表现出高水平的疲劳和身心症状，这些症状与血液透析相关，并由透析诱导的炎症通路、Wnt/连环蛋白信号通路及铜的变化介导。
