PTM-Fetuin-A: A Novel Biomarker for Early Detection of Diabetic Kidney Disease
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Abstract
Chronic Kidney Disease (CKD) is a significant public health issue with a rising prevalence globally. Diabetic kidney disease (DKD), a leading cause of CKD, necessitates improved biomarkers for early detection and effective management. Traditional markers such as serum creatinine, estimated glomerular filtration rate (eGFR), and albuminuria have notable limitations in sensitivity and specificity, especially for early detection. Fetuin-A, specifically its post-translationally modified form (PTM-Fetuin-A), has emerged as a potential novel biomarker for DKD. This study evaluates PTM-Fetuin-A in a cohort of Bulgarian patients with type 1 and type 2 diabetes, assessing its correlation with traditional markers such as albuminuria and eGFR. Significant correlations were observed between PTM-Fetuin-A and these indicators (e.g., Pearson’s r = 0.447, p = 0.025 for albuminuria), highlighting its ability to detect early kidney function decline. Furthermore, PTM-Fetuin-A demonstrated potential as a non-invasive tool for identifying normoalbuminuric DKD, addressing gaps left by conventional biomarkers. By offering additional prognostic value, PTM-Fetuin-A could improve the early diagnosis and clinical management of diabetic patients, reducing the burden of CKD.
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KDIGO. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3(1):1-150. Available from: https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf
Levin A, Ahmed SB, Carrero JJ, Foster B, Francis A, Hall RK, et al. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S). Available from: https://kdigo.org/wp-content/uploads/2017/02/KDIGO-2024-CKD-Guideline-Executive-Summary.pdf
United States Renal Data System. USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2023. Available from: https://usrds-adr.niddk.nih.gov/2023
Wolf GB, Ziyadeh FN. Molecular mechanisms of diabetic renal hypertrophy. Kidney Int. 1999;56(2):393–405. Available from: http://dx.doi.org/10.1046/j.1523-1755.1999.00590.x
International Diabetes Federation. IDF Diabetes Atlas. 10th ed. Brussels, Belgium: International Diabetes Federation; 2021. Available from: https://diabetesatlas.org/atlas/tenth-edition/
American Diabetes Association. Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S1-S291. Available from: https://diabetesjournals.org/care/issue/46/Supplement_1
Rule AD, Larson TS, Bergstralh EJ, Slezak JM, Jacobsen SJ, Cosio FG. Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease. Ann Intern Med. 2004;141(12):929-37. Available from: https://doi.org/10.7326/0003-4819-141-12-200412210-00009
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604-612. Available from: https://doi.org/10.7326/0003-4819-150-9-200905050-00006
Bakris GL, Molitch M. Microalbuminuria as a risk predictor in diabetes: The continuing saga. Diabetes Care. 2014;37(3):867-875. Available from: https://doi.org/10.2337/dc13-1870
Alkaff FF, Kremer D, Niekolaas TM, van den Born J, Rimbach G, Tseng TL, et al. Urinary vanin-1, tubular injury, and graft failure in kidney transplant recipients. Sci Rep. 2024;14:2283. Available from: https://doi.org/10.1038/s41598-024-52635-x
Al-Khoury S, Afzali B, Shah N, Covic A, Thomas S, Goldsmith DJ. Anaemia in diabetic patients with chronic kidney disease—prevalence and predictors. Diabetologia. 2006;49:1183-9. Available from: https://doi.org/10.1007/s00125-006-0254-z
Abebe CE, Muche ZT, Mariam AT, Ayele TM, Agidew MM, Azezew MT, et al. The structure, biosynthesis, and biological roles of fetuin-A: A review. Front Cell Dev Biol. 2022;10:945287. Available from: https://doi.org/10.3389/fcell.2022.945287
Ricken F, Can AD, Gräber S, Häusler M, Jahnen-Dechent W. Post-translational modifications glycosylation and phosphorylation of the major hepatic plasma protein fetuin-A are associated with CNS inflammation in children. PLoS One. 2022;17(10):e0268592. Available from: https://doi.org/10.1371/journal.pone.0268592
Schaefer C, Boegemann N, Eismann U. Fetuin-A and its role in calcium and bone metabolism in CKD. Kidney Blood Press Res. 2018;43(6):1798-1805.
Dzhanaev R, Hasberg C, Gorgels A, Schmitz C, Winkler CF, Malyaran H, et al. Application of the mineral-binding protein fetuin-A for the detection of calcified lesions. Theranostics. 2023;13(2):659-672. Available from: https://doi.org/10.7150/thno.78773
Ix JH, Shlipak MG, Brandenburg VM, Ali S, Ketteler M, Whooley MA. Association between human fetuin-A and the metabolic syndrome: data from the Heart and Soul Study. Circulation. 2006;113(14):1760-7. Available from: https://doi.org/10.1161/circulationaha.105.588723
Musolino M, Greco M, D'Agostino M, Tripodi L, Misiti R, Dragone F, et al. Urinary Post-Translationally Modified Fetuin-A (uPTM-FetA) in Chronic Kidney Disease Patients with and without Diabetic Kidney Disease. Medicina (Kaunas). 2024;60(3):363. Available from: https://doi.org/10.3390/medicina60030363
Chu D, Wang Y, He Y. Urinary Fetuin-A as a potential biomarker for diabetic nephropathy. Nephrology. 2022;27(8):644-650.
Chuanga K, Nguyen C, Nair A. Potential of PTM-Fetuin-A in predicting kidney function decline in diabetes. Diabetes Res Clin Pract. 2024;190:109985.
Chuang GT, Kremer D, Huang CH, Alkaff FF, Lin CH, Tseng TL, et al. Urinary fetuin-A fragments predict progressive eGFR decline in two independent type 2 diabetes cohorts of different ethnicities. Am J Nephrol. 2024;55:106-114. Available from: https://doi.org/10.1159/000534514
Catanese L, Siwy J, Mavrogeorgis E, Amann K, Mischak H, Beige J, et al. A Novel Urinary Proteomics Classifier for Non-Invasive Evaluation of Interstitial Fibrosis and Tubular Atrophy in Chronic Kidney Disease. Proteomes. 2021;9(3):32. Available from: https://doi.org/10.3390/proteomes9030032
Kumar Bandi R, Eghbali-Fatourechi G, Ahmed SB, et al. Evaluation of PTM-Fetuin-A as a biomarker for CKD progression. Clin Nephrol. 2022;98(3):135-142.
Bandi VK, Narilla NSSH, Chaganti S, Yarlagadda S, Eadala S, et al. #6545 Urinary Fetuin-A Fragment Excretion In Patients With Type 2 Diabetes And Its Correlation With Renal Function. Nephrol Dial Transplant. 2023;38(Suppl_1):gfad063c_6545. Available from: https://doi.org/10.1093/ndt/gfad063c_6545
Chuang LM, Huang CH, Lin CH, Tseng TL. POS-362 Development Of Biomarkers For Predicting Dkd Progression In Non-Proteinuric Type 2 Diabetes: The Ntuh-Dkd Cohort Study. Kidney Int Rep. 2022;7(2):S163. Available from: https://doi.org/10.1016/j.ekir.2022.01.384