Gembillo G, Soraci L, Spadaro G, Messina R, Cuzzola F, Calderone M, Ricca MF, Di Piazza S, Sudano F, Gambuzza ME, Princiotto M, Lo Cicero L, Santoro D. Serum biomarkers in diabetic kidney disease: A comprehensive narrative review. World J Diabetes 2026; 17(4): 113748 [DOI: 10.4239/wjd.v17.i4.113748]
Corresponding Author of This Article
Guido Gembillo, MD, Doctor, Unit of Nephrology and Dialysis, AOU “G. Martino”, University of Messina, Via Consolare Valeria, 1, Messina 98125, Sicilia, Italy. guidogembillo@live.it
Research Domain of This Article
Medicine, General & Internal
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Apr 15, 2026; 17(4): 113748 Published online Apr 15, 2026. doi: 10.4239/wjd.v17.i4.113748
Serum biomarkers in diabetic kidney disease: A comprehensive narrative review
Guido Gembillo, Luca Soraci, Giuseppe Spadaro, Rossella Messina, Felicia Cuzzola, Michela Calderone, Maria Federica Ricca, Simona Di Piazza, Flavia Sudano, Maria Elsa Gambuzza, Maria Princiotto, Lorenzo Lo Cicero, Domenico Santoro
Guido Gembillo, Giuseppe Spadaro, Rossella Messina, Felicia Cuzzola, Michela Calderone, Maria Federica Ricca, Simona Di Piazza, Flavia Sudano, Lorenzo Lo Cicero, Domenico Santoro, Unit of Nephrology and Dialysis, AOU “G. Martino”, University of Messina, Messina 98125, Sicilia, Italy
Luca Soraci, Unit of Geriatric Medicine, Italian National Research Center on Aging (IRCCS INRCA), Cosenza 87100, Calabria, Italy
Maria Elsa Gambuzza, Territorial Office of Messina, Ministry of Health, Messina 98125, Sicilia, Italy
Maria Princiotto, Laboratory of Pharmacoepidemiology and Biostatistics, Italian National Research Center on Aging (IRCCS INRCA), Cosenza 87100, Calabria, Italy
Co-corresponding authors: Guido Gembillo and Luca Soraci.
Author contributions: Gembillo G, Lo Cicero L, Santoro D, and Soraci L contributed to the literature search; Gembillo G, Santoro D, Spadaro G, and Cuzzola F contributed to conceptualization; Calderone M, Messina R, Di Piazza S, Gambuzza ME, and Princiotto M contributed to study selection; Gembillo G, Lo Cicero L, Ricca MF, Soraci L, and Sudano F contributed to manuscript drafting; Gembillo G and Soraci L played indispensable roles in experimental design, data interpretation and manuscript preparation as the co-corresponding authors; all authors have read and agreed to the published version of the manuscript.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Corresponding author: Guido Gembillo, MD, Doctor, Unit of Nephrology and Dialysis, AOU “G. Martino”, University of Messina, Via Consolare Valeria, 1, Messina 98125, Sicilia, Italy. guidogembillo@live.it
Received: September 2, 2025 Revised: December 5, 2025 Accepted: February 6, 2026 Published online: April 15, 2026 Processing time: 224 Days and 13.6 Hours
Abstract
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. Traditional biomarkers such as serum creatinine and estimated glomerular filtration rate lack sensitivity for early kidney injury detection, limiting timely intervention. This review comprehensively evaluates serum biomarkers for DKD, focusing on their diagnostic and prognostic utility, mechanistic insights, and clinical applicability. Novel serum biomarkers, including cystatin C, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and tumor necrosis factor receptors (TNFRs) (TNFR1, TNFR2), demonstrate superior sensitivity for early renal damage and progression prediction. Emerging markers, such as adropin, soluble urokinase plasminogen activator receptor, monocyte chemoattractant protein-1, chitinase-3-like protein 1, endostatin, zinc-alpha-2-glycoprotein, PromarkerD, and circulating microRNAs offer additional risk stratification potential. Integrating validated serum biomarkers may enhance early DKD detection, enable precise risk stratification, and support personalized therapeutic strategies to improve patient outcomes.
Core Tip: Diabetic kidney disease is the main cause of end-stage renal disease, yet early detection is limited by the poor sensitivity of serum creatinine and estimated glomerular filtration rate. Novel biomarkers such as cystatin C, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and tumor necrosis factor receptors show superior accuracy for identifying early damage and predicting progression. Emerging markers, including adropin, soluble urokinase plasminogen activator receptor, monocyte chemoattractant protein-1, chitinase-3-like protein 1, endostatin, zinc-α2-glycoprotein, PromarkerD, and microRNAs, provide additional value for risk stratification and personalized therapy. Integration of validated multi-marker panels may transform monitoring and management, improving outcomes for patients with diabetes.
