Assessment of ELISA-based method for the routine examination of serum indoxyl sulfate in patients with chronic kidney disease

Shuangdi Duan; Jiayi Pi; Chun-Hsiang Wang; Yi-Chou Hou; Chung-Ying Andy Lee; Cheng-Jui Lin; Liyang Shi; Kung-Chia Young; Hung-Yu Sun

doi:10.1016/j.heliyon.2022.e12220

Assessment of ELISA-based method for the routine examination of serum indoxyl sulfate in patients with chronic kidney disease

Heliyon. 2022 Dec 14;8(12):e12220. doi: 10.1016/j.heliyon.2022.e12220. eCollection 2022 Dec.

Authors

Shuangdi Duan^{1

2}, Jiayi Pi^{1

2}, Chun-Hsiang Wang³, Yi-Chou Hou^{4

5}, Chung-Ying Andy Lee⁶, Cheng-Jui Lin^{7

8

9}, Liyang Shi¹, Kung-Chia Young^{10

11

12}, Hung-Yu Sun^{11

13}

Affiliations

¹ College of Biology, Hunan University, Changsha 410082, China.
² Institute of Pathogen Biology and Immunology of College of Biology, Hunan Provincial Key Laboratory of Medical Virology, Hunan University, Changsha 410082, China.
³ Division of Gastroenterology, Tainan Municipal Hospital, Tainan 700, Taiwan.
⁴ Division of Nephrology, Department of Medicine, Cardinal-Tien Hospital, New Taipei City 23148, Taiwan.
⁵ School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan.
⁶ Dalian Zhen-Ao Bio-Tech Co., Ltd, Dalian 116000, China.
⁷ Division of Nephrology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 100, Taiwan.
⁸ Department of Medicine, Mackay Medical College, New Taipei City 252, Taiwan.
⁹ Mackay Junior College of Medicine, Nursing and Management, Taipei 100, Taiwan.
¹⁰ Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
¹¹ Institute of Basic Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
¹² Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
¹³ Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Abstract

Introduction: Indoxyl sulfate (IS), a protein-bound uremic toxin, is associated with kidney function and chronic kidney disease (CKD)-related complications. Currently, serum IS levels are primarily quantified using mass spectrometry-based methods, which are not feasible for routine clinical examinations.

Methods: The efficiencies of three commercial ELISA kits in determination of serum IS were validated by comparing with ultra-performance liquid chromatography (UPLC)-MS/MS-based method using Bland-Altman analysis. The associations between kidney parameters and serum IS levels determined by ELISA kit from Leadgene and UPLC-MS/MS were evaluated by Spearman correlation coefficient in a CKD validation cohort.

Results: ELISA kit from Leadgene showed clinical agreement with UPLC-MS/MS in the determination of serum IS levels (p = 0.084). In patients with CKD, Spearman's correlation analysis revealed a perfect correlation between the IS levels determined using the Leadgene ELISA kit and UPLC-MS/MS (r = 0.964, p < 0.0001). IS levels determined using the Leadgene ELISA kit were associated with the estimated glomerular filtration rate (r = -0.772, p < 0.0001) and serum creatinine concentration (r = 0.824, p < 0.0001) in patients with CKD, and on dialysis (r = 0.557, p = 0.006).

Conclusions: The Leadgene ELISA kit exhibits comparable efficacy to UPLC-MS/MS in quantifying serum IS levels, supporting that ELISA would be a personalized method for monitoring the dynamic changes in serum IS levels in dialysis patients to prevent the progression of CKD.

Keywords: Chronic kidney disease; ELISA; Indoxyl sulfate; UPLC-MS/MS.