Kidoguchi Shuhei, Torii Kunio, Okada Toshiharu, Yamano Tomoko, Iwamura Nanami, Miyagi Kyoko, Toyama Tadashi, Iwano Masayuki, Miyazaki Ryoichi, Shigematsu Yosuke, Kimura Hideki
Department of Clinical Laboratory, University of Fukui Hospital, Fukui 910-1193, Japan.
Department of Clinical Laboratory, Japanese Red Cross Fukui Hospital, Fukui 918-8501, Japan.
Diagnostics (Basel). 2024 Oct 16;14(20):2295. doi: 10.3390/diagnostics14202295.
BACKGROUND/OBJECTIVES: Lipid metabolism and adiponectin modulate erythropoiesis in vitro and in general population studies and may also affect responsiveness to erythropoietin in patients undergoing haemodialysis (HD). However, little is known about the impact of lipid-associated biomarkers on reticulocyte production and erythropoietin resistance index (ERI) in patients undergoing HD. Therefore, we aimed to investigate their impacts in 167 stable patients undergoing HD.
Pre-dialysis blood samples were collected and analysed for reticulocyte counts and serum lipid profiles by routine analyses and serum carnitine profiles (C0-C18) by LC-MS/MS. ERI was calculated as erythropoietin dose/kg/week normalized for haemoglobin levels.
The independent positive determinants of reticulocyte count were log [Triglyceride (TG)] and logC18:1. A large proportion of longer-chain acylcarnitines was positively correlated with reticulocyte counts, possibly resulting from the accumulation of acylcarnitines in mitochondria undergoing fateful exocytosis from reticulocytes. These results indicate a possible association between reticulocyte formation and reduced β-oxidation, which occurs during the peripheral phase of erythroblast enucleation. Total cholesterol (TC) and log [C2/(C16 + C18:1)] as a putative marker of β-oxidation efficiency were negative independent determinants of ERI. Moreover, acyl chain length had a significantly positive impact on the correlation coefficients of individual acylcarnitines with ERI, suggesting that enhanced β-oxidation may be associated with reduced ERI. Finally, adiponectin had no independent association with reticulocyte counts or ERI despite its negative association with HDL-C levels.
Enhanced fatty acid β-oxidation and higher TC levels may be associated with lower ERI, whereas higher TG levels and longer acylcarnitines may be related to the latest production of reticulocytes in stable patients undergoing HD.
背景/目的:脂质代谢和脂联素在体外及一般人群研究中调节红细胞生成,也可能影响血液透析(HD)患者对促红细胞生成素的反应性。然而,关于脂质相关生物标志物对HD患者网织红细胞生成和促红细胞生成素抵抗指数(ERI)的影响知之甚少。因此,我们旨在研究它们对167例稳定HD患者的影响。
采集透析前血样,通过常规分析检测网织红细胞计数和血清脂质谱,通过液相色谱-串联质谱法检测血清肉碱谱(C0 - C18)。ERI计算为根据血红蛋白水平标准化的促红细胞生成素剂量/千克/周。
网织红细胞计数的独立正向决定因素是log[甘油三酯(TG)]和logC18:1。大部分长链酰基肉碱与网织红细胞计数呈正相关,这可能是由于酰基肉碱在经历网织红细胞致命性胞吐作用的线粒体中积累所致。这些结果表明网织红细胞形成与红细胞去核外周阶段发生的β-氧化减少之间可能存在关联。总胆固醇(TC)和作为β-氧化效率推定标志物的log[C2/(C16 + C18:1)]是ERI的负向独立决定因素。此外,酰基链长度对个体酰基肉碱与ERI的相关系数有显著正向影响,表明增强的β-氧化可能与降低的ERI相关。最后,尽管脂联素与高密度脂蛋白胆固醇(HDL-C)水平呈负相关,但与网织红细胞计数或ERI无独立关联。
脂肪酸β-氧化增强和较高的TC水平可能与较低的ERI相关,而较高的TG水平和较长的酰基肉碱可能与稳定HD患者中网织红细胞的最新生成有关。