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Differences in AGEs-N-Carboxymethyllysine and Kidney Injury Molecule-1 in non-diabetic subjects, diabetic with and without diabetic nephropathy

  • Dwi Fajaryani ,
  • Muji Rahayu ,
  • Banundari Rachmawati ,


Background: Diabetic nephropathy (ND) is a complication of diabetes mellitus (DM), characterized by persistent albuminuria. N-carboxymethyl lysine (CML) is the most extensive advanced glycation end products (AGEs), formed from the fructoselysine amadori. Kidney Injury Molecule 1 (KIM-1) is a type 1 transmembrane glycoprotein. The aim of the study is to analyze the differences in AGEs-CML and KIM-1 levels in the non-DM subject, DM without and with DN.

Methods: A cross-sectional analytic observational study was conducted on 25 non-DM subjects (K1), 25 DM without DN (K2), and 25 DM with  DN (K3) in PROLANIS Semarang. AGEs-CML and KIM-1 levels were measured using the ELISA method. Inter-group AGEs-CML levels were analyzed using the One way ANOVA test, followed by post hoc Games-Howell. The levels KIM-1 between groups were analyzed using the Kruskal-Wallis test levels, followed by Mann Whitney post hoc test and p<0.05, were considered significant.

Results: There were differences in AGEs-CML levels between K1 (739.89±227.37 ng/ml) and K3 (911.79±107.44) (p = 0.005), between K2 (798.82±153.03) and K3 (911.79 ± 107.44) (p = 0.012) and there was no difference in K1 and K2 (p =0.535). There were differences in KIM-1 level between K1 [9.82 (5.99 – 14.83) pg/ml] and K2 [15.31 (10.12 – 30.21) (p <0.001)], between K1 [9.82 (5.99 – 14.83)] and K3 [15.11 (8.27 – 25.63) (p <0.001)] and there was no difference between K2 and K3 (p=0.720)

Conclusion: The highest AGEs-CML levels were significantly found in the K3 group, followed by K2 and the lowest in K3. KIM-1 levels were significantly found in the K2 group, followed by K3 and the lowest in K1.


  1. Soelistijo SA, Novida H, Rudijanto A, Pradana S, Suastika K, Manaf A. Consensus on the Management and Prevention of Type 2 Diabetes Mellitus in Indonesia 2015. Indonesian Diabetic Association. 2015.
  2. Riddle MC. The Journal of clinical and applied research and Education Diabetes Care. Am Diabetes Assoc. 2019;42:204.
  3. International Diabetes Federations response to the 3rd UN HLM on NCDs political declaration. IDF. 2018;1–10.
  4. Mihardja L, Delima D, Massie RGA, Karyana M, Nugroho P, Yunir E. Prevalence of kidney dysfunction in diabetes mellitus and associated risk factors among productive age Indonesian. J Diabetes Metab Disord. 2018;17(29):53–61.
  5. Gheith O, Farouk N, Nampoory N, Halim MA, Al-otaibi T. Diabetic kidney disease: world wide difference of prevalence and risk factor. J Nephropharmacol. 2016;5(1):49–56.
  6. Olokoba AB, Obateru OA, Olokoba LB. Type 2 diabetes mellitus: a review of current trends. Oman Med J. 2012;27(4):269-73. doi: 10.5001/omj.2012.68
  7. Lim AKh. Diabetic nephropathy - complications and treatment. Int J Nephrol Renovasc Dis. 2014;7:361-81. doi: 10.2147/IJNRD.S40172.
  8. Persson F, Rossing P. Diagnosis of diabetic kidney disease: state of the art and future perspective. Kidney Int Suppl. 2018;8(1):2–7.
  9. Lee SY, Chol ME. Albuminuria, Urinary biomarkers for early diabetic nephropathy: Beyond. HHS Public Access. 2016;30(7):1063–75.
  10. Robles NR, Villa J, Gallego RH. Non-Proteinuric Diabetic Nephropathy. J Clin Med. 2015;4:1761–73.
  11. Gluhovschi C, Gluhovschi G, Petrica L, Timar R, Velciov S, Ionita I, Kaycsa A, Timar B. Urinary Biomarkers in the Assessment of Early Diabetic Nephropathy. J Diabetes Res. 2016;2016:4626125. doi: 10.1155/2016/4626125.
  12. Uwaezuoke SN. The role of novel biomarkers in predicting diabetic nephropathy : a review. Int J Nephrol Renovasc Dis. 2017;10:221–31.
  13. Rabbani N, Thornalley PJ. Advanced glycation end products in the pathogenesis of chronic kidney disease. Kidney Int. 2018;93(4):803–13.
  14. Brings S, Fleming T, Freichel M, Muckenthaler MU, Herzig S, Nawroth PP. Dicarbonyls and Advanced Glycation End-Products in the Development of Diabetic Complications and Targets for Intervention. Int J Mol Sci. 2017;18(5):984. doi: 10.3390/ijms18050984.
  15. Wada J, Makino H. Inflammation and the pathogenesis of diabetic nephropathy. Clin Sci. 2013;152:139–52.
  16. Tang SCW, Leung CK, Neng K. Diabetic Tubulopathy: An Emerging Entity. Diabetes and the kidney. 2011;170:124–34.
  17. Petrica L, Vlad A, Gluhovschi G, Zamfir A, Popescu C, Gadalean F, et al. Glycated peptides are associated with proximal tubule dysfunction in type 2 diabetes mellitus. Int J Clin. 2015;8(2):2516–25.
  18. Moresco RN, Bochi G V, Stein CS, Carvalho JAM De, Cembranel BM, Bollick YS. Clinica Chimica Acta Urinary kidney injury molecule-1 in renal disease. Clin Chim Acta. 2018;487:15–21.
  19. Gale EAM, Gillespie KM. Diabetes and gender. Diabetologia. 2001;44:3–15.
  20. Retnakaran R, Cull CA, Thorne KI, Adler AI, Holman RR. Risk Factors for Renal Dysfunction in Type 2 Diabetes. Diabetes. 2006;55:1832–9.
  21. Gitanjali G, Goyal S, Panag K. Role of Urinary Albumin To Creatinine Ratio and Spot Albuminuria in Predicting Significant Albuminuria in Patients of Diabetic Nephropathy. J Evol Med Dent Sci. 2014;3(01):38–45.
  22. Lim A. Diabetic nephropathy – complications and treatment. Int J Nephrol Renovasc Dis. 2014;47:361–81.
  23. Meigs J, D’Agostino R, Nathan D, Rifai N, Wilson P. Longitudinal Association of Glycemia and Microalbuminuria The Framingham Offspring Study. Epidemiol Heal Serv Psychosoc Res. 2002;25(6):977–83.
  24. Tervaert TWC, Mooyaart AL, Amann K, Cohen AH, Cook HT, Drachenberg CB, et al. Pathologic Classification of Diabetic Nephropathy. J Am Soc Nephrol. 2010;21:556–63.
  25. Coughlan MT, Patel K, Jerums G, Penfold A, Macisaac RJ, Forbes M. Advanced Glycation Urinary Protein-Bound Biomarkers and Severity of Diabetic Nephropathy in Man. Am J Nephrol. 2011;34:347–55.
  26. Friess U, Waldner M, Wahl HG, Lehmann R, Haring HU, Voelter W, et al. Liquid chromatography-based determination of urinary free and total N(epsilon)-(carboxymethyl)lysine excretion in normal and diabetic subjects. J Chromatogr B Anal Technol Biomed Life Sci. 2003;794(2):273–80.
  27. Wagner Z, Wittmann I, Mazak I, Schinzel R, Heidland A, Kientsch-Engel R. N-Carboxymethyllysine Levels in Patients With Type 2 Diabetes: Role of Renal Function. Am J kidney Dis. 2001;38(4):785–91.
  28. Morcos M, Sayed AAR, Bierhaus A, Yard B, Merz W, Kloeting I, et al. Activation of Tubular Epithelial Cells in Diabetic. Diabetes. 2002;51:21–4.
  29. Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV. Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int. 2002;62(1):237-44. doi: 10.1046/j.1523-1755.2002.00433.x.
  30. Aslan O, Demir M, Koseoglu M. Kidney Injury Molecule Levels in Type 2 Diabetes Mellitus. J Clin Lab Anal. 2016;1036:1031–6.
  31. Ahmed SA, Hamed MA. Kidney injury molecule-1 as a predicting factor for inflamed kidney , diabetic and diabetic nephropathy Egyptian patients. Journal diabetes Metab Disord. 2015;14(6):1–6.
  32. Zylka A, Paulina D, Beata C, Anieszka B, Piotr C. Markers of Glomerular and Tubular Damage in the Early Stage of Kidney Disease in Type 2 Diabetic Patients. Mediators of Inflammation. 2018;1–12.
  33. Tekce BK. Evaluation of the Urinary Kidney Injury Molecule-1 Levels in Patients With Diabetic Nephropathy. 2014;37(6):377–83.

How to Cite

Fajaryani, D., Rahayu, M., & Rachmawati, B. (2021). Differences in AGEs-N-Carboxymethyllysine and Kidney Injury Molecule-1 in non-diabetic subjects, diabetic with and without diabetic nephropathy. Bali Medical Journal, 10(1), 325–330.




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