Iwata Yasunori, Nakade Yusuke, Kinoshita Masashi, Sabit Hemragul, Nakajima Riho, Furuichi Kengo, Mita Masashi, Nakane Maiko, Sakai Norihiko, Kitajima Shinji, Toyama Tadashi, Miyagawa Taro, Hara Akinori, Shimizu Miho, Sato Kouichi, Oshima Megumi, Nakagawa Shiori, Yamamura Yuta, Ogura Hisayuki, Koshino Yoshitaka, Nakada Mitsutoshi, Wada Takashi
Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan.
Division of Infection Control, Kanazawa University Hospital, Kanazawa, Japan.
Kidney Dis (Basel). 2023 Jan 13;9(2):118-129. doi: 10.1159/000527798. eCollection 2023 Apr.
The number of patients with chronic kidney disease (CKD) is increasing worldwide. Cognitive impairment is one of the comorbidities of CKD. With the increased number of aged population, novel biomarkers of impaired cognitive function are required. Intra-body profile of amino acid (AA) is reportedly altered in patients with CKD. Although some AAs act as neurotransmitters in the brain, it is not clear whether altered AA profile are associated with cognitive function in patients with CKD. Therefore, intra-brain and plasma levels of AAs are evaluated with respect to cognitive function in patients with CKD.
Plasma levels of AAs were compared between 14 patients with CKD, including 8 patients with diabetic kidney disease, and 12 healthy controls to identify the alteration of specific AAs in CKD. Then, these AAs were evaluated in the brains of 42 patients with brain tumor using non-tumor lesion of the resected brain. Cognitive function is analyzed with respect to intra-brain levels of AAs and kidney function. Moreover, plasma AAs were analyzed in 32 hemodialyzed patients with/without dementia.
In patients with CKD, plasma levels of asparagine (Asn), serine (Ser), alanine (Ala), and proline (Pro) were increased as compared to patients without CKD. Among these AAs, L-Ser, L-Ala, and D-Ser show higher levels than the other AAs in the brain. Intra-brain levels of L-Ser was correlated with cognitive function and kidney function. The number of D-amino acid oxidase or serine racemase-positive cells was not correlated with kidney function. Moreover, the plasma levels of L-Ser are also decreased in patients with declined cognitive function who are treated with chronic hemodialysis.
The decreased levels of L-Ser are associated with impaired cognitive function in CKD patients. Especially, plasma L-Ser levels may have a potential for novel biomarker of impaired cognitive function in patients with hemodialysis.
全球慢性肾脏病（CKD）患者数量正在增加。认知障碍是CKD的合并症之一。随着老年人口数量的增加，需要新的认知功能受损生物标志物。据报道，CKD患者体内氨基酸（AA）谱发生改变。虽然一些氨基酸在大脑中充当神经递质，但尚不清楚AA谱改变是否与CKD患者的认知功能相关。因此，针对CKD患者的认知功能，对其脑内和血浆中的氨基酸水平进行了评估。
比较了14例CKD患者（包括8例糖尿病肾病患者）和12例健康对照者的血浆氨基酸水平，以确定CKD中特定氨基酸的变化。然后，使用切除脑的非肿瘤病变，对42例脑肿瘤患者脑内的这些氨基酸进行评估。针对脑内氨基酸水平和肾功能分析认知功能。此外，还对32例有/无痴呆的血液透析患者的血浆氨基酸进行了分析。
与非CKD患者相比，CKD患者血浆中天冬酰胺（Asn）、丝氨酸（Ser）、丙氨酸（Ala）和脯氨酸（Pro）水平升高。在这些氨基酸中，L-丝氨酸、L-丙氨酸和D-丝氨酸在脑中的水平高于其他氨基酸。脑内L-丝氨酸水平与认知功能和肾功能相关。D-氨基酸氧化酶或丝氨酸消旋酶阳性细胞的数量与肾功能无关。此外，接受慢性血液透析且认知功能下降的患者血浆L-丝氨酸水平也降低。
L-丝氨酸水平降低与CKD患者认知功能受损有关。特别是，血浆L-丝氨酸水平可能有潜力成为血液透析患者认知功能受损的新型生物标志物。
