Syndecan-1 as a Prognostic Biomarker for Early Diabetic Kidney Disease Progression: A Cohort Study

DOI: https://doi.org/10.62517/jmpe.202518506

Author(s)

Yiqun Peng1, Dongguang Wang1, Kaifa Guo1,*, Liang Peng2,3,*

Affiliation(s)

1Department of Agriculture and Biotechnology, Hunan University of Humanities, Science and Technology. Loudi, China 2Department of Nephrology, The Second Affiliated Hospital of the University of South China, Hengyang, China 3Department of Nephrology, Loudi Central hospital of Hunan Province, Loudi, China *Corresponding author

Abstract

This study aimed to investigate the role of serum Syndecan-1 levels in the progression of Diabetic kidney disease (DKD) and their predictive value for adverse renal outcomes. Two hundred thirty-eight participants were included in the study cohort, consisting of 90 DKD patients (estimated glomerular filtration rate (eGFR)>60ml/min/1.73m2), 88 diabetes mellitus(DM) patients without kidney disease, and 60 healthy individuals. Baseline levels of Syndecan-1 and relevant clinical indicators were measured for all participants. A 2-year follow-up study defined the primary endpoint as a ≥30% drop in eGFR or an eGFR below 60 mL/min/1.73 m², and the secondary endpoint as a ≥30% rise in proteinuria. Multivariate logistic regression and ROC curve analysis were used. Baseline Syndecan-1 levels differed significantly among the three groups: the DKD group had substantially higher Syndecan-1 levels than the DM group, while the healthy group had the lowest levels. DKD patients were divided into high and low Syndecan-1 expression groups, with the high-expression group experiencing more primary and secondary endpoint events. Multivariate logistic regression analysis confirmed that baseline Syndecan-1 concentration was an independent risk factor for both proteinuria progression and eGFR decline in DKD patients (P<0.05).ROC curve analysis demonstrated that Syndecan-1 had a specific predictive value for DKD progression (AUC = 0.804, P<0.05). Syndecan-1 is highly expressed in DKD patients and is independently associated with adverse renal outcomes. It may serve as a potential biomarker for assessing the risk of DKD progression.

Keywords

Diabetes Mellitus; Diabetic Kidney Disease; Syndecan-1; Progression

References

[1]Luxia Z, Fang W, Li W, Wenke W, Bicheng L, Jian L, Menghua C, Qiang H, Yunhua L, Xueqing Y et al: Prevalence of chronic kidney disease in China: a cross-sectional survey. Lancet 2012, 379(9818). [2]Sonali G, Mary D, Ladan G: Diabetic Kidney Disease: An Update. Med Clin North Am 2023, 107(4). [3]Sopida T: Early detection of diabetic nephropathy in patient with type 2 diabetes mellitus: A review of the literature. Diab Vasc Dis Res 2021, 18(6). [4]Jiayun Y, Caiyan Z, Yaodong W, Tingyan L, Zhenhao Y, Kexin W, Weiming C, Yufeng Z, Guoping L: Sulodexide improves vascular permeability via glycocalyx remodelling in endothelial cells during sepsis. Front Immunol 2023, 14(0). [5]Ryo U, Eric P S, Nathan I S: The glycocalyx: a novel diagnostic and therapeutic target in sepsis. Crit Care 2019, 23(1). [6]Derih A, Mesut E, Sadık Ahmet S, Filiz A, Rahime Feyza K, Yasemin U, Senol Y, Ahmet Fatih Ö: Syndecan-1 as a marker to predict acute kidney injury after isolated coronary artery bypass graft operations. Rev Assoc Med Bras (1992) 2023, 69(1). [7]Radu-Stefan M, Irina-Iuliana C, Daniela C, Ovidiu M, Amalia-Stefana T, Monica H, Daniela-Anicuta L, Ionela-Larisa M, Raul-Alexandru J, Alexandru-Florinel O et al: Syndecan-1: From a Promising Novel Cardiac Biomarker to a Surrogate Early Predictor of Kidney and Liver Injury in Patients with Acute Heart Failure. Life (Basel) 2023, 13(4). [8]K G A, P Z Z: Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998, 15(7). [9]Andrew S L, Lesley A S, Christopher H S, Yaping Lucy Z, Alejandro F 3rd C, Harold I F, John W K, Paul E, Frederick VL, Tom G et al: A new equation to estimate glomerular filtration rate. Ann Intern Med 2009, 150(9). [10]Yi-Chih L, Yu-Hsing C, Shao-Yu Y, Kwan-Dun W, Tzong-Shinn C: Update of pathophysiology and management of diabetic kidney disease. J Formos Med Assoc 2018, 117(8). [11]Mai S, Wai Lun Will P, Tetsuhiro T, Sydney C W T, Masaomi N: Update on diagnosis, pathophysiology, and management of diabetic kidney disease. Nephrology (Carlton) 2021, 26(6). [12]Chan-Young J, Tae-Hyun Y: Pathophysiologic Mechanisms and Potential Biomarkers in Diabetic Kidney Disease. Diabetes Metab J 2022, 46(2). [13]Rui T, Ranran L, Yang C, Di L, Yinjiaozhi L, Shiyuan H, Tingting P, Hongping Q, Ruoming T: Shenfu injection ameliorates endotoxemia-associated endothelial dysfunction and organ injury via inhibiting PI3K/Akt-mediated glycolysis. J Ethnopharmacol 2024, 335(0). [14]Man G, Jiarui X, Shuan Z, Daoqi S, Wuhua J, Lin Z, Xiaoqiang D, Xialian X: Suppressing Syndecan-1 Shedding to Protect Against Renal Ischemia/Reperfusion Injury by Maintaining Polarity of Tubular Epithelial Cells. Shock 2021, 57(2). [15]Daoqi S, Liyu L, Yiqi S, Ying H, Yaqiong W, Jiarui X, Wuhua J, Zhen Z, Xiaoqiang D, Xialian X: Syndecan-1 regulates lipid metabolism and mitigates fibrosis during the transition from acute kidney injury to chronic kidney disease. Metabolism 2025, 172(0).