Novel Biomarkers in Diabetic Kidney Disease: A Comparative Analysis

Authors

DOI:

https://doi.org/10.32007/jfacmedbaghdad3341

Keywords:

Biomarkers, Diabetic Kidney Disease, GPR120, Midkine, Podoplanin

Abstract

Background: Diabetic Nephropathy is a serious microvascular complication of Type II Diabetes Mellitus that requires specific biomarkers for early detection.
Objective: This study was conducted as a comparative analysis of serum  G-protein-coupled receptor 120 (GPR120) as a key modulator of metabolic and renal health, leading to its comparison with Midkine and Podoplanin for assessing renal impairment in diabetic patients.
Methods: A case-control study conducted from September 2025 to February 2026 at the Imam Hussein Medical City Dialysis Center and Imam Hasan Center for Endocrinology and Diabetes in Iraq involved 120 participants aged 30 to 70 years, including Type II Diabetes Mellitus patients and age-matched controls.
Results: Significant differences in serum levels of GPR120, Midkine, and Podoplanin were noted, with GPR120 demonstrating superior diagnostic performance for both diabetes mellitus and diabetic nephropathy. Midkine effectively identified nephropathy cases, showing higher serum levels in nephropathy patients compared to diabetes mellitus patients and healthy controls. Although serum Podoplanin levels were also elevated in nephropathy patients, GPR120 levels were lower across both patient groups. Receiver Operating Characteristic (ROC) analysis indicated that GPR120 possessed the highest diagnostic accuracy overall, while Midkine showed strong performance for nephropathy and Podoplanin displayed limited capabilities for diabetes mellitus.
Conclusion: GPR120 is established as a promising biomarker for diagnosing diabetes mellitus and diabetic nephropathy, enhancing clinical utility for early detection of diabetic renal disease, with Midkine serving as a complementary marker, whereas Podoplanin's effectiveness is limited. The study underscores the potential role of these biomarkers in improving patient outcomes.

Received: 04 April 2026, Revised:10 Aug. 2026, Accepted: 13 Aug. 2026, Published Online: Sept. 2026

References

1. Sun H, Saeedi P, Karuranga S, et al. IDF Diabetes Atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183:109119. https://doi.org/10.1016/j.diabres.2021.109119.

2. Sugahara M, Pak WL, Tanaka T, et al. Update on diagnosis, pathophysiology, and management of diabetic kidney disease. Nephrology (Carlton). 2021;26(6):491-500. https://doi.org/10.1111/nep.13860.

3. Młynarska E, Buławska D, Czarnik W, et al. Novel insights into diabetic kidney disease. Int J Mol Sci. 2024;25(18):10222. https://doi.org/10.3390/ijms251810222.

4. Zelniker TA, Braunwald E. Mechanisms of cardiorenal effects of sodium-glucose cotransporter 2 inhibitors: JACC state-of-the-art review. J Am Coll Cardiol. 2020;75(4):422-434. https://doi.org/10.1016/j.jacc.2019.11.031.

5. Xu Y, Zhao L, Mi Y, et al. Serum Midkine as a Potential Biomarker Associated with Disease Severity and Remodeling-Related Mediators in Children with Asthma. J Asthma Allergy. 2026;19. https://doi.org/10.2147/JAA.S570351.

6. Metwalley KA, Farghaly HS, Gabri MF, et al. Midkine: utility as a predictor of early diabetic nephropathy in children with type 1 diabetes mellitus. J Clin Res Pediatr Endocrinol. 2021;13(3):293-299. https://doi.org/10.4274/jcrpe.galenos.2021.2020.0303.

7. Cai YQ, Lv Y, Mo ZC, et al. Multiple pathophysiological roles of midkine in human disease. Cytokine. 2020;135:155242. https://doi.org/10.1016/j.cyto.2020.155242.

8. Suzuki H, Kaneko MK, Kato Y. Roles of podoplanin in malignant progression of tumor. Cells. 2022;11(3):575. https://doi.org/10.3390/cells11030575.

9. Zhang Z, Zhang N, Yu J, et al. The role of podoplanin in the immune system and inflammation. J Inflamm Res. 2022;15:3561-3572. https://doi.org/10.2147/JIR.S366620.

10. Wang H, Yang M, Liu X, et al. G protein-coupled receptor-mediated renal fibrosis: a key focus on kidney disease drug development. Front Pharmacol. 2025;16:1645888. https://doi.org/10.3389/fphar.2025.1645888.

11. Lv L, Liu Y, Xiong J, et al. Role of G protein coupled receptors in acute kidney injury. Cell Commun Signal. 2024;22:423. https://doi.org/10.1186/s12964-024-01802-8.

12. Hasan N, Chhabra KH. Glucose sensing and homeostasis by adipocyte GPCR. Front Endocrinol (Lausanne). 2025;16:1657747. https://doi.org/10.3389/fendo.2025.1657747.

13. Oliveira de Souza C, Sun X, Oh D. Metabolic functions of G protein-coupled receptors and β-arrestin-mediated signaling pathways in the pathophysiology of type 2 diabetes and obesity. Front Endocrinol (Lausanne). 2021;12:715877. https://doi.org/10.3389/fendo.2021.715877.

14. Hultström M, Becirovic-Agic M, Jönsson S. Comparison of acute kidney injury of different etiology reveals in-common mechanisms of tissue damage. Physiol Genomics. 2018;50(3):127-141. https://doi.org/10.1152/physiolgenomics.00037.2017.

15. Xu C, Chen J, Liang L, et al. Midkine promotes renal fibrosis by stabilizing C/EBPβ to facilitate endothelial-mesenchymal transition. Commun Biol. 2024;7(1):544. https://doi.org/10.1038/s42003-024-06154-0.

16. Quintanilla M, Montero-Montero L, Renart J, et al. Podoplanin in inflammation and cancer. Int J Mol Sci. 2019;20(3):707. https://doi.org/10.3390/ijms20030707.

17. Huan F, Jiang X. Serum podoplanin levels as a potential biomarker for diabetic nephropathy progression: a cross-sectional study. Diabetes Metab Syndr Obes. 2024;17:4701-4710. https://doi.org/10.2147/DMSO.S500608.

18. Pei G, Yao Y, Yang Q, et al. Lymphangiogenesis in kidney and lymph node mediates renal inflammation and fibrosis. Sci Adv. 2019;5(6):eaaw5075. https://doi.org/10.1126/sciadv.aaw5075.

19. Li JJ, Kwak SJ, Jung DS, et al. Podocyte biology in diabetic nephropathy. Kidney Int Suppl. 2007;(106):S36-S42. https://doi.org/10.1038/sj.ki.5002384.

20. Shankland SJ. The podocyte's response to injury: role in proteinuria and glomerulosclerosis. Kidney Int. 2006;69(12):2131-2147. https://doi.org/10.1038/sj.ki.5000410.

21. Sato W, Sato Y. Midkine in nephrogenesis, hypertension and kidney diseases. Br J Pharmacol. 2014;171(4):879-887. https://doi.org/10.1111/bph.12418.

22. Tonneijck L, Muskiet MH, Smits MM, et al. Glomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment. J Am Soc Nephrol. 2017;28(4):1023-1039. https://doi.org/10.1681/ASN.2016060666.

23. Barutta F, Bellini S, Gruden G. Mechanisms of podocyte injury and implications for diabetic nephropathy. Clin Sci (Lond). 2022;136(7):493-520. https://doi.org/10.1042/CS20210625.

24. Varney MJ, Benovic JL. The role of G protein-coupled receptors and receptor kinases in pancreatic β-cell function and diabetes. Pharmacol Rev. 2024;76(2):267-299. https://doi.org/10.1124/pharmrev.123.001015.

25. Wu Y, Wang Y, Zhang J, et al. Early-onset of type 2 diabetes mellitus is a risk factor for diabetic nephropathy progression: a biopsy-based study. Aging (Albany NY). 2021;13(6):8146-8154. https://doi.org/10.18632/aging.202624.

26. Zarjou A, Black LM, Bolisetty S, et al. Dynamic signature of lymphangiogenesis during acute kidney injury and chronic kidney disease. Lab Invest. 2019;99(9):1376-1388. https://doi.org/10.1038/s41374-019-0259-0.

27. Campbell VK, Gately RP, Krishnasamy R, et al. Midkine and chronic kidney disease-associated multisystem organ dysfunctions. Nephrol Dial Transplant. 2021;36(9):1577-1584. https://doi.org/10.1093/ndt/gfaa084.

biomarkers; CKD; Diabetic Kidney Disease

Downloads

Issue

Online First

Section

Articles

Categories

How to Cite

1.
Abduljabbar AA, Sarhat ER, Al-Ghanimi HH, Alobaidy HF. Novel Biomarkers in Diabetic Kidney Disease: A Comparative Analysis. J Fac Med Baghdad [Internet]. [cited 2026 Sep. 20];. Available from: https://iqjmc.uobaghdad.edu.iq/index.php/19JFacMedBaghdad36/article/view/3341