Retrospective Cohort Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jun 15, 2024; 15(6): 1212-1225
Published online Jun 15, 2024. doi: 10.4239/wjd.v15.i6.1212
Evaluating new biomarkers for diabetic nephropathy: Role of α2-macroglobulin, podocalyxin, α-L-fucosidase, retinol-binding protein-4, and cystatin C
Jing-Jing Li, Ru-La Sa, Yu Zhang, Zhao-Li Yan
Jing-Jing Li, Department of Infectious Diseases, Inner Mongolia Medical University, Hohhot First Hospital, Hohhot 010000, Inner Mongolia Autonomous Region, China
Ru-La Sa, Zhao-Li Yan, Department of Endocrinology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010000, Inner Mongolia Autonomous Region, China
Yu Zhang, Department of Dermatology, Inner Mongolia Autonomous Region People’s Hospital, Hohhot 010000, Inner Mongolia Autonomous Region, China
Author contributions: Li JJ and Sa RL designed the research; Li JJ, Zhang Y, and Yan ZL performed the research; Zhang Y and Yan ZL contributed new reagents/analytic tools; Li JJ and Sa RL analyzed the data; Li JJ, Sa RL, and Zhang Y wrote the paper.
Supported by the Natural Science Foundation of Inner Mongolia Autonomous Region, No. 2022MS08057.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the Affiliated Hospital of Inner Mongolia Medical University (Approval No. WZ2024004).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The author declares no conflict of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhao-Li Yan, FAASLD, Chief Doctor, Research Fellow, Department of Endocrinology, The Affiliated Hospital of Inner Mongolia Medical University, No. 1 Tongdao North Road, Hohhot 010000, Inner Mongolia Autonomous Region, China. aliceyzl@126.com
Received: January 7, 2024
Revised: February 27, 2024
Accepted: April 30, 2024
Published online: June 15, 2024
Processing time: 154 Days and 5.4 Hours
Abstract
BACKGROUND

The intricate relationship between type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) presents a challenge in understanding the significance of various biomarkers in diagnosis.

AIM

To elucidate the roles and diagnostic values of α2-macroglobulin (α2-MG), podocalyxin (PCX), α-L-fucosidase (AFU), retinol-binding protein-4 (RBP-4), and cystatin C (CysC) in DN.

METHODS

From December 2018 to December 2020, 203 T2DM patients were enrolled in the study. Of these, 115 were diagnosed with DN (115 patients), while the remaining 88 patients were classified as non-DN. The urinary levels of α2-MG, PCX, and AFU and the serum concentrations RBP-4 and CysC were measured in conjunction with other relevant clinical indicators to evaluate their potential correlations and diagnostic utility.

RESULTS

After adjustments for age and gender, significant positive correlations were observed between the biomarkers CysC, RBP-4, α2-MG/urinary creatinine (UCr), PCX/UCr, and AFU/UCr, and clinical indicators such as urinary albumin-to-creatinine ratio (UACR), serum creatinine, urea, 24-h total urine protein, and neutrophil-to-lymphocyte ratio (NLR). Conversely, these biomarkers exhibited negative correlations with the estimated glomerular filtration rate (P < 0.05). Receiver operating characteristic (ROC) curve analysis further demonstrated the diagnostic performance of these biomarkers, with UACR showcasing the highest area under the ROC curve (AUCROC) at 0.97.

CONCLUSION

This study underscores the diagnostic significance of α2-MG, PCX, and AFU in the development of DN. The biomarkers RBP-4, CysC, PCX, AFU, and α2-MG provide promising diagnostic insights, while UACR is the most potent diagnostic biomarker in assessing DN.

Keywords: α2-macroglobulin; Podocalysin; α-L-fucosidase; Retinol binding protein-4; Cystatin C; Diabetic nephropathy

Core Tip: This study elucidates the diagnostic value of α2-macroglobulin (α2-MG), podocalyxin (PCX), α-L-fucosidase (AFU), retinol-binding protein-4 (RBP-4), and cystatin C (CysC) in type 2 diabetes mellitus and diabetic nephropathy (DN). It reveals that these biomarkers, especially urinary albumin to creatinine ratio (UACR), are strongly correlated with renal damage indicators. The research demonstrates the superior diagnostic capability of UACR for DN, while highlighting the importance of α2-MG, PCX, AFU, RBP-4, and CysC as complementary diagnostic tools. These findings provide valuable insights into the mechanisms of DN and enhance diagnostic accuracy in clinical practice.