Novel Biomarkers in the Early Detection of Chronic Kidney Disease: Current Evidence and Future Directions
DOI:
https://doi.org/10.70749/ijbr.v3i5.1480Keywords:
Chronic Kidney Disease, Early Detection, Biomarkers, Proteomics, Metabolomics, Exosomes, Machine LearningAbstract
Chronic kidney disease (CKD) affects over 850 million individuals worldwide, with conventional markers failing to detect early renal damage until significant nephron loss occurs. This review synthesizes current evidence on emerging biomarkers—including proteomic signatures (e.g., CKD273 panel), metabolomics profiles, circulating microRNAs, APOL1 genetic variants, cell-free DNA methylation patterns, and urinary exospores that enable earlier detection of CKD. We examine multi-marker panels integrated with machine-learning algorithms, achieving high sensitivity and specificity in prospective cohorts, and assess point-of-care technologies facilitating decentralized screening. Regulatory and ethical challenges, cost-effectiveness analyses, and standardization hurdles across diverse healthcare settings are also discussed. Finally, we identify research gaps in longitudinal, multi-center validation studies and propose future directions toward precision nephrology, integrating multi-omics data with imaging and wearable sensors to shift CKD management from treatment to prevention. This comprehensive overview informs clinicians and researchers on the translational potential of novel diagnostics in combating the growing CKD burden.
Downloads
References
Alobaidi S. Emerging Biomarkers and Advanced Diagnostics in Chronic Kidney Disease: Early Detection Through Multi-Omics and AI. Diagnostics. 2025;15(10):1225.
https://www.mdpi.com/2075-4418/15/10/1225/pdf
Alobaidi S. Emerging Biomarkers and Advanced Diagnostics in Chronic Kidney Disease: Early Detection Through Multi-Omics and AI. Diagnostics. 2025;15(10):1225.
https://doi.org/10.3390/diagnostics15101225
Alobaidi, S. (2025). Emerging biomarkers and advanced diagnostics in chronic kidney disease: Early detection through multi-omics and AI. *Diagnostics*, 15(10), 1225.
https://doi.org/10.3390/diagnostics15101225
Alobaidi, S. M. (2025). Emerging Biomarkers and Advanced Diagnostics in Chronic Kidney Disease: Early Detection Through Multi-Omics and AI – A Review. Diagnostics, 15(10), 1225.
https://doi.org/10.3390/diagnostics15101225
Altamura S., Pietropaoli D., Lombardi F., Del Pinto R., Ferri C. (2023). An overview of chronic kidney disease pathophysiology: the impact of gut dysbiosis and oral disease. *Biomedicines*, 11(11):3033.
https://doi.org/10.3390/biomedicines11113033
Benito, S., Sánchez-Ortega, A., Unceta, N., Goicolea, M. A., & Barrio, R. J. (2024). Untargeted metabolomics for plasma biomarker discovery for early chronic kidney disease diagnosis in pediatric patients using LC-QTOF-MS. *Scientific Reports*, 14, 62518.
https://doi.org/10.1038/s41598-024-62518-w
Berezina TA, Berezin AE. Cell-free DNA as a plausible biomarker of chronic kidney disease. Epigenomics. 2023;15(17):879-890. Available from:
https://www.tandfonline.com/doi/full/10.2217/epi-2023-0255
Božić, J., Kumrić, M., Bošnjak, I., et al. (2022) “Emerging biomarkers for early detection of chronic kidney disease,” *International Journal of Molecular Sciences*, 23(6), p. 354.
https://doi.org/10.3390/ijms23063054
Cañadas-Garre M, Anderson K, McGoldrick J, Maxwell AP, McKnight AJ. Proteomic and metabolomic approaches in the search for biomarkers in chronic kidney disease. J Proteomics. 2019;193:93–122. [Full Text]
https://doi.org/10.1016/j.jprot.2018.09.020
Cao H, Li Z, Ye J, et al. Emerging roles of exosomes in the diagnosis and treatment of kidney diseases. Front Pharmacol. 2025;16:1525314.
https://doi.org/10.3389/fphar.2025.1525314
Catanese L, Siwy J, Mischak H, Wendt R, Beige J, Rupprecht H. Recent Advances in Urinary Peptide and Proteomic Biomarkers in Chronic Kidney Disease: A Systematic Review. Int J Mol Sci. 2023;24(11):9156.
https://www.mdpi.com/1422-0067/24/11/9156/pdf
Catanese L, Siwy J, Mischak H, Wendt R, Beige J, Rupprecht H. Recent Advances in Urinary Peptide and Proteomic Biomarkers in Chronic Kidney Disease: A Systematic Review. International Journal of Molecular Sciences. 2023;24(11):9156.
https://doi.org/10.3390/ijms24119156
Chen X, et al. A systematic review of epigenetic interplay in kidney diseases. Clin Epigenet. 2024;16:62.
https://www.sciencedirect.com/science/article/pii/S0753332224008060
Di Dio, M., Filicetti, E., Greco, G. I., et al. (2024) “Biomarkers of chronic kidney disease in older individuals: navigating complexity in diagnosis,” *Frontiers in Medicine*, 12, p. 1397160.
https://doi.org/10.3389/fmed.2024.1397160
Frąk W., Kućmierz J., Szlagor M., Młynarska E., Rysz J., Franczyk B. (2022). New insights into molecular mechanisms of chronic kidney disease. *Biomedicines*, 10(11):846.
https://doi.org/10.3390/biomedicines10112846
Francis, A., Harhay, M. N., Ong, A. C. M., et al. (2024) “Chronic kidney disease and the global public health agenda: an international consensus,” *Nature Reviews Nephrology*, 20, pp. 473–485.
https://doi.org/10.1038/s41581-024-00820-6
Giuliani K. T. K., Adams B. C., Healy H. G., Kassianos A. J. (2024). Regulated cell death in chronic kidney disease: current evidence and future clinical perspectives. *Frontiers in Cell and Developmental Biology*, 12:1497460. Available at
https://doi.org/10.3389/fcell.2024.1497460
Gunasekara TDKSC, De Silva PMCS, Herath C, et al. The Utility of Novel Renal Biomarkers in Assessment of Chronic Kidney Disease of Unknown Etiology (CKDu): A Review. International Journal of Environmental Research and Public Health. 2020;17(23):9522.
https://doi.org/10.3390/ijerph17249522
Gupta A, Sontakke T, Acharya S, Kumar S, et al. A Comprehensive Review of Biomarkers for Chronic Kidney Disease in Older Individuals: Current Perspectives and Future Directions. Cureus. 2024;16(9):e70262.
https://doi.org/10.7759/cureus.70262
Gupta, D., et al. (2023). Facilitators and barriers of the implementation of point-of-care testing for cardiometabolic conditions: a scoping review using CFIR. BMC Health Services Research. Available at:
https://bmchealthservres.biomedcentral.com/articles/10.1186/s12913-023-09419-2
He, X., & Li, H. (2025). Long Non-Coding RNAs in Chronic Kidney Disease: Pathogenesis, Diagnosis and Therapeutic Potential. Cell Biochemistry and Biophysics, 83(2), 170–186.
https://doi.org/10.1007/s12013-025-01698-2
Heerspink, H. J. L., Agarwal, R., Bakris, G. L.; FIND-CKD Investigators (2025) “Systems biology and novel biomarkers for the early detection of chronic kidney disease,” *Nephrology Dialysis Transplantation*, 40(2), pp. 29–37
https://doi.org/10.1093/ndt/gfae132
Joshi N, Garapati K, Ghose V, Kandasamy RK, Pandey A. Recent progress in mass spectrometry-based urinary proteomics. Clin Proteomics. 2024;21(1):14. [Full Text]
https://clinicalproteomicsjournal.biomedcentral.com/articles/10.1186/s12014-024-09462-z/pdf
Joshi, P. R. (2024). Advancements in biomarkers for early detection of chronic kidney disease: A review. *Journal of Nephrology & Therapeutics*, 14, 532.
https://doi.org/10.37421/2161-0959.2024.14.532
KDIGO. 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024. https://kdigo.org/wp-content/uploads/2024/03/KDIGO-2024-CKD-Guideline.pdf
Korsa, A., Tesfaye, W., Sud, K., Krass, I., & Castelino, R. L. (2025). Risk factor-based screening for early detection of chronic kidney disease in primary care settings: A systematic review. *Kidney Medicine*, 7(4), 100979.
https://doi.org/10.1016/j.xkme.2025.100979
Kumar, P., Singh, R. & Patel, M. (2025) “Application of biomarkers in the diagnosis of kidney disease,” *Frontiers in Medicine*, 12, p. 1560222.
https://doi.org/10.3389/fmed.2025.1560222
Latosinska A, Siwy J, Faguer S, Beige J, Mischak H, Schanstra JP. Value of Urine Peptides in Assessing Kidney and Cardiovascular Disease. Proteomics Clin Appl. 2021;15(1):e2000027. [Full Text]
https://onlinelibrary.wiley.com/doi/10.1002/prca.202000027
Lee J, et al. Screening, identifying, and treating chronic kidney disease: a review of guideline-based screening approaches. BMC Nephrol. 2024.
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03466-5
Lee, J., et al. (2024). Wearable sensors for monitoring chronic kidney disease. Communications Engineering.
https://www.nature.com/articles/s43246-024-00606-0
Li, S., Hu, W., Qian, L., & Sun, D. (2025). Non-Coding RNAs in Kidney Disease: A Review of Long Non-Coding RNAs and microRNAs. Molecular and Cellular Biochemistry, 480(3), 1287–1304.
https://doi.org/10.1007/s11010-024-05083-0
Liu AP, Sun TJ, Liu TY, et al. Urinary exosomes as promising biomarkers for early kidney disease detection. Am J Clin Exp Urol. 2025;13(1):1-19.
https://e-century.us/files/ajceu/13/1/ajceu0161856.pdf e-century.us
Liu C, Debnath N, Mosoyan G, et al. Systematic Review and Meta-Analysis of Plasma and Urine Biomarkers for CKD Outcomes. Journal of the American Society of Nephrology. 2022;33(7):1657–1672.
https://doi.org/10.1681/ASN.2022010098
Martin, G., et al. (2024). Current implementation of digital health in chronic disease management: a scoping review. Journal of Medical Internet Research.
https://www.jmir.org/2024/1/e53576/
Medina, D. D., Matshazi, D. M., & Erasmus, R. T. (2023). Circulating microRNAs as Early Biomarkers of Chronic Kidney Disease: Systematic Review. International Journal of Molecular Sciences, 24(2), 1792.
https://doi.org/10.3390/ijms24021792
Mizdrak M, Kumrić M, Kurir TT, Božić J. Emerging Biomarkers for Early Detection of Chronic Kidney Disease. Journal of Personalized Medicine. 2022;12(4):548.
https://doi.org/10.3390/jpm12040548
Mizdrak, M., Kumrić, M., Kurir, T. T., & Božić, J. (2022). Emerging biomarkers for early detection of chronic kidney disease. *Journal of Personalized Medicine*, 12(4), 548
https://doi.org/10.3390/jpm12040548
Morozova, O. L., Kuznetsova, L. B., Baranskaya, F. M., & Ivanov, P. A. (2023). CKD Urine Metabolomics: Modern Concepts and Approaches. Pathophysiology, 30(4), 443–466.
https://doi.org/10.3390/pathophysiology30040033
Murtagh FE, et al. Kidney function estimation equations: a narrative review. Irish Journal of Medical Science. 2025. https://link.springer.com/article/10.1007/s11845-025-03874-y
Nguyen, H., et al. (2023). Miniaturized bio- and chemical-sensors for point-of-care monitoring of CKD biomarkers. Biosensors & Bioelectronics. Available at:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5948530/
Nichols M, et al. A comprehensive review of advanced biomarkers for CKD in older adults: current insights and future directions. Cureus. 2024.
https://doi.org/10.7759/cureus.70413
Pandey, S., Sharma, A., & Gupta, R. (2025). Metabolomics for the Identification of Biomarkers in Kidney Diseases: A Review. International Journal of Molecular Sciences, 26(4), 1723.
https://doi.org/10.3390/ijms26041723
Patel M, et al. Epigenetic alterations and memory: key players in AKI-to-CKD transition. Kidney Int. 2024;105(4):817-827. https://www.kidney-international.org/article/S0085-2538(24)00918-9/fulltext
Patel, R., et al. (2024). Cost-effectiveness of screening for chronic kidney disease: a systematic review. International Journal of Health Economics and Management.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10765095/
Pianca NJ, et al. Beyond creatinine: New methods to measure renal function? Nat Rev Nephrol. 2025.
https://www.sciencedirect.com/science/article/abs/pii/S0953620525000251
Pradeep U, Chiwhane A, Acharya S, et al. A comprehensive review of biomarkers for chronic kidney disease in older individuals: current perspectives and future directions. 2024.
https://doi.org/10.7759/cureus.70262
Pu C, Xu W. Novel Biomarkers for Kidney Disease: New Frontiers in Early Diagnosis and Monitoring. Academic J Sci Technol. 2024;12(2):217–222. [Full Text]
https://drpress.org/ojs/index.php/ajst/article/view/25630
Ramirez, L., et al. (2023). Economic evaluations of screening programs for chronic kidney disease: a systematic review. Value in Health.
https://www.sciencedirect.com/science/article/pii/S1098301523030929
Reiss A. B., Jacob B., Zubair A., Srivastava A., Johnson M., De Leon J. (2022). Fibrosis in Chronic Kidney Disease: Pathophysiology and Therapeutic Targets. *Journal of Clinical Medicine*, 13(7):1881.
https://doi.org/10.3390/jcm13071881
Roumeliotis, S., Divani, M., Stamellou, E., & Liakopoulos, V. (2024). Genomic Insights into Diabetic Kidney Disease: A 2024 Update. Current Genomics, 25(3), 153–157.
https://doi.org/10.2174/1389202925666240325080421
Rysz J, Gluba-Brzózka A, Franczyk B, Jabłonowski Z, Ciałkowska-Rysz A. Novel Biomarkers in the Diagnosis of Chronic Kidney Disease and the Prediction of its Outcome. International Journal of Molecular Sciences. 2017;18(8):1702.
https://doi.org/10.3390/ijms18081702
Saeidinezhad Z, et al. Management of chronic kidney disease: The current novel and traditional biomarkers – Implications for clinical practice. World Sci News. 2024.
https://www.sciencedirect.com/science/article/pii/S2214623724000255
Salazar, A., Ferreira, C., Oliveira, P., et al. (2021). New potential biomarkers for chronic kidney disease management—a review of the literature. *International Journal of Molecular Sciences*, 22(1), 43
https://doi.org/10.3390/ijms22010043
Sandokji, I., Xu, Y., Denburg, M., Furth, S. L., Abraham, A. G., & Greenberg, J. H. (2024). Current and novel biomarkers of progression risk in children with chronic kidney disease. *Nephron*, 148(1), 1–10.
https://doi.org/10.1159/000530918
Sen T., Kale A., Lech M., Anders H. J., Gaikwad A. B. (2023). Promising novel therapeutic targets for kidney disease: emphasis on kidney-specific proteins. *Drug Discovery Today*, 28:103466.
https://doi.org/10.1016/j.drudis.2022.103466
Shabaka A., Cases-Corona C., Fernandez-Juarez G. (2021). Therapeutic insights in chronic kidney disease progression. *Frontiers in Medicine*, 8:645187.
https://doi.org/10.3389/fmed.2021.645187
Shahin A, et al. Biomarkers of chronic kidney disease in older individuals. Front Med. 2024.
https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1397160/full
Srinivasan, V., et al. (2024). Point-of-care biosensors and devices for diagnostics of chronic kidney disease. Sustainable Chemistry & Diagnostics.
https://pubs.rsc.org/en/content/articlelanding/2024/sd/d4sd00241e
Szczech, L. A. & Smoyer, W. E. (2024) “Epigenetic modifications as novel biomarkers of CKD progression,” *Clinical Epigenetics*, 16(1), p. 204.
https://doi.org/10.1186/s13148-024-02048-3
Tuttle K. R., Agarwal R., Alpers C. E., et al. (2022). Molecular mechanisms and therapeutic targets for diabetic kidney disease. *Kidney International*, 102(2):248–260.
https://doi.org/10.1016/j.kint.2022.05.012
Villa-Bellosta, R., Manzur, F., & Rodríguez, C. (2025). Genetic Variants and Chronic Kidney Disease Progression: A Systematic Review. Genes, 14(1), 68.
https://doi.org/10.3390/genes14010068
Villalvazo P, Villavicencio C, Gonzalez de Rivera M, Fernandez-Fernandez B, Ortiz A. Systems Biology and Novel Biomarkers for the Early Detection of Diabetic Kidney Disease. Nephron. 2025;149(1):29–35.
https://www.karger.com/DOI/10.1159/000540307
Villalvazo P, Villavicencio C, Gonzalez de Rivera M, Fernandez-Fernandez B, Ortiz A. Systems Biology and Novel Biomarkers for the Early Detection of Diabetic Kidney Disease. Nephron. 2025;149(1):29–35.
https://doi.org/10.1159/000540307
Villalvazo, P., Villavicencio, C., Gonzalez de Rivera, M., et al. (2025). Systems biology and novel biomarkers for the early detection of diabetic kidney disease. *Nephron*, 149(1), 29–35.
https://doi.org/10.1159/000540307
Wang, X., Xie, Y., Wei, L. & Xu, Z. (2025) “Metabolomic approaches in the discovery of biomarkers for chronic kidney disease,” *Metabolomics*, 21(1), p. 14.
https://doi.org/10.1007/s11306-024-02102-4
Yuan Q., Tang B., Zhang C. (2022). Signaling pathways of chronic kidney diseases, implications for therapeutics. *Signal Transduction and Targeted Therapy*.
https://doi.org/10.1038/s41392-022-01036-5
Zhang M, Cai Y, Zhong X, et al. Effects of cell-free DNA on kidney disease and intervention strategies. Front Pharmacol. 2024;15:1377874. https://www.frontiersin.org/articles/10.3389/fphar.2024.1377874/full
Zhang, X., et al. (2024). An account of the current status of point-of-care lateral flow tests for renal biomarker detection. Analyst. https://pubs.rsc.org/en/content/articlehtml/2024/an/d4an00806e
Zhang, Y., Li, H. & Wang, T. (2025) “Emerging biomarkers and advanced diagnostics in chronic kidney disease,” *Diagnostics*, 15(10), p. 1225.
https://doi.org/10.3390/diagnostics15101225
Zheng Y, Wang H, Li X, et al. Extracellular vesicles in chronic kidney disease: diagnostic and therapeutic roles. Front Pharmacol. 2024;15:1371874.
https://doi.org/10.3389/fphar.2024.1371874.
Zhong W, et al. Unraveling the epigenetic code: human kidney DNA methylation changes in CKD. Nat Commun. 2024;15:45295.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Indus Journal of Bioscience Research

This work is licensed under a Creative Commons Attribution 4.0 International License.
