Intra-Brain and Plasma Levels of L-Serine Are Associated with Cognitive Status in Patients with Chronic Kidney Disease

Yasunori Iwata; Yusuke Nakade; Masashi Kinoshita; Hemragul Sabit; Riho Nakajima; Kengo Furuichi; Masashi Mita; Maiko Nakane; Norihiko Sakai; Shinji Kitajima; Tadashi Toyama; Taro Miyagawa; Akinori Hara; Miho Shimizu; Kouichi Sato; Megumi Oshima; Shiori Nakagawa; Yuta Yamamura; Hisayuki Ogura; Yoshitaka Koshino; Mitsutoshi Nakada; Takashi Wada

doi:10.1159/000527798

Intra-Brain and Plasma Levels of L-Serine Are Associated with Cognitive Status in Patients with Chronic Kidney Disease

Kidney Dis (Basel). 2023 Jan 13;9(2):118-129. doi: 10.1159/000527798. eCollection 2023 Apr.

Authors

Yasunori Iwata^{1

2}, Yusuke Nakade¹, Masashi Kinoshita³, Hemragul Sabit³, Riho Nakajima⁴, Kengo Furuichi⁵, Masashi Mita⁶, Maiko Nakane⁶, Norihiko Sakai^{1

7}, Shinji Kitajima^{1

7}, Tadashi Toyama¹, Taro Miyagawa¹, Akinori Hara¹, Miho Shimizu¹, Kouichi Sato¹, Megumi Oshima¹, Shiori Nakagawa¹, Yuta Yamamura¹, Hisayuki Ogura¹, Yoshitaka Koshino⁸, Mitsutoshi Nakada³, Takashi Wada¹

Affiliations

¹ Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan.
² Division of Infection Control, Kanazawa University Hospital, Kanazawa, Japan.
³ Department of Neurosurgery, Kanazawa University, Kanazawa, Japan.
⁴ Department of Occupational Therapy, Kanazawa University, Kanazawa, Japan.
⁵ Division of Nephrology, Kanazawa Medical University School of Medicine, Kanazawa, Japan.
⁶ KAGAMI Inc., Ibaraki, Japan.
⁷ Division of Blood Purification, Kanazawa University Hospital, Kanazawa, Japan.
⁸ Department of Internal Medicine, Mizuho Hospital, Kahoku, Japan.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Chronic kidney disease; Cognitive impairment; L-Serine.

Grants and funding

This work was supported by JSPS KAKENHI (21K08224, YI) (21K07315 YN), Kanazawa University SAKIGAKE project 2020 (YI), and the Japan Agency for Medical Research and Development (TW).