Urinarni biomarkeri u ranoj dijagnozi dijabetesne bolesti bubrega i dijabetesne retinopatije

  • Brankica Terzic VMA
Ključne reči: Ključne reči: dijabetes melitus, mikroalbuminurija, biomarkeri, kolagen tip IV, transferin, L-FABP

Sažetak


Uvod/Cilj

Urinarni biomarkeri predstavljaju značajne indikatore renalne lezije kod pacijenata sa dijabetesom tipa 2, a pojedini od njih mogu ukazivati i na rani nastanak mikrovaskularnih komplikacija.Dijabetesna bolest bubrega (DBB) je najčešća mikrovaskularna komplikacija dijabetesa i vodeći uzrok hronične bubrežne bolesti i terminalne bubrežne insuficijencije. Iako je mikrolabuminurija prihvaćeni rani marker bubrežnog oštećenja, njena ograničena snzitivnosti i specifičnost nameću potrebu za novim urinarnim biomarkerima koji bi omogućili raniju dijagnozu renalnog oboljenja. Cilj ove studije bio je da se proceni da li urinarni kolagen tip IV, transferin i vezujući protein masnih kiselina jetre (L-FABP) mogu poslužiti kao rani biomarkeri dijabetesne bolesti bubrega, kao i da se ispita njihova povezanost sa dijabetesnom retinopatijom

Metode

Studija je uključila 80 pacijenata sa dijabetesom tipa 2, podeljenih u dve grupe: grupa 1 – normoalbuminurični (≤30 mg/dan) i grupa 2 – mikroalbuminurični (30–300 mg/dan). Deset zdravih osoba je služilo kao kontrolna grupa. Svi ispitanici  su bili  stariji od 18 godina, sa trajanjem dijabetesa dužim od jedne godine I procenjenom  jačinom  glomerulske filtracije (eGFR) >60 ml/min/1,73 m². Koncentracije kolagena tip IV, transferina i L-FABP određivane su u 24-časovnim i prvim jutarnjim uzorcima urina primenom visoko senzitivnih ELISA testova. Statistička analiza obuhvatila je poredjenje grupa, testiranje korelacija I procenu dijagnostičkih performansi pomoću ROC krive.

Rezultati

Urinarne koncentracije svih ispitivanih  biomarkera  su  bile zanemarljive  kod zdravih kontrola, ali su bile značajno više kod mikroalbuminuričnih u poređenju sa normoalbuminuričnim pacijentima (p < 0.05). Najveći dijagnostički potencijal za rano otkrivanje DKD  imao je kolagen tip IV (90,4%). Svi biomerkeri su pokazali pozitivnu korelaciju sa prisustvom DKD, dok je urinarni transferrin dodatno bio povezan sa dijabetesnom retinopatijom.

Zaključak

Urinarni kolagen tipa IV, transferin i L-FABP predstavljaju obećavajuće rane biomarkere dijabetesne bubrežne bolesti, sa većim dijagnostičkim potencijalom u poređenju sa albuminurijom. Pored toga, urinarni transferin može služiti kao neinvazivni marker za rano otkrivanje dijabetesne retinopatije, što potvrđuje njegovu ulogu u praćenju mikrovaskularnih komplikacija kod pacijenata sa dijabetes melitusom tipa 2.

 

 

 

 

Biografija autora

Brankica Terzic, VMA
Nefrologija

Reference

References

1. International Diabetes Federation (IDF). IDF Diabetes Atlas 11th edition. idf.org. 2025.

2. Dash S, Chougule A, Mohanty S. Correlation of Albuminuria and Diabetic Retinopathy in Type-II Diabetes Mellitus Patients. Cureus. 2022 Feb 5;14(2):e21927. doi: 10.7759/cureus.21927.

3. Zhen LT, Yih-Chung T, Marco YM Li Chee, Tyler HR, Ning C, Mukharram M.B, Xing YW, et al.Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045: Systematic Review and Meta-analysis,Ophthalmology,Volume 128, Issue 11,2021, Pages 1580-1591,ISSN 0161-6420, https://doi.org/10.1016/j.ophtha.2021.04.027.76

4. Li et al. Research progress on the pathogenesis of diabetic retinopathy BMC Ophthalmology (2023) 23:372 https://doi.org/10.1186/s12886-023-03118-6

5. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney DiseaseVOL 105 | ISSUE 4S | APRIL 2024Kidney International (2024) 105 (Suppl 4S), S117–S314

6. Gupta S, Dominguez M, Golestaneh L. Diabetic Kidney Disease: An Update. Med Clin North Am. 2023 Jul;107(4):689-705. doi: 10.1016/j.mcna.2023.03.004

7. AS L, Coresh J, Balk E, Al E. National kidney foundation practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Ann Intern Med. 2003;139(2):137–47

8. Samsu N. Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment. Biomed Res Int. 2021 Jul 8;2021:1497449. doi: 10.1155/2021/1497449.

9. Gaydarski, L., Petrova, K., Angushev, I., Stanchev, S., Iliev, A., Stamenov, N., Kirkov, V., & Landzhov, B. (2025). Exploring the Molecular Modalities in the Pathogenesis of Diabetic Kidney Disease with a Focus on the Potential Therapeutic Implications. Biomedicines, 13(1), 50. https://doi.org/10.3390/biomedicines13010050

10. McGill JB, Haller H, Roy-Chaudhury P, Cherrington A, Wada T, Wanner C, Ji L, Rossing P. Making an impact on kidney disease in people with type 2 diabetes: the importance of screening for albuminuria. BMJ Open Diabetes Res Care. 2022 Jul;10 (4):e002806. doi: 10.1136/bmjdrc-2022-002806.

11. Uchenna A. N, Jeanne A. D, Kenneth K. C, Zeng B, Arzumanyan H, Joan C. Lo, Zheng S; Prevalence of Albuminuria Among Adults With Diabetes and Preserved Estimated Glomerular Filtration Rate by Race and Ethnicity. Diabetes Care 1 March 2023; 46 (3): e78–e80. https://doi.org/10.2337/dc22-1871

12. Scilletta, S., Di Marco, M., Miano, N., Filippello, A., Di Mauro, S., Scamporrino, A., Musmeci, M., Coppolino, G., Di Giacomo Barbagallo, F., Bosco, G., Scicali, R., Piro, S., Purrello, F., & Di Pino, A. (2023). Update on Diabetic Kidney Disease (DKD): Focus on Non-Albuminuric DKD and Cardiovascular Risk. Biomolecules, 13(5), 752. https://doi.org/10.3390/biom13050752

13. Zhang C, Liu T, Wang X, Yang J, Qin D, Liang Y, Wang X. Urine biomarkers in type 2 diabetes mellitus with or without microvascular complications. Nutr Diabetes. 2024 Jul 10;14(1):51. doi: 10.1038/s41387-024-00310-5

14. Swaminathan SM, Rao IR, Shenoy SV, Prabhu AR, Mohan PB, Rangaswamy D, Bhojaraja MV, Nagri SK, Nagaraju SP. Novel biomarkers for prognosticating diabetic kidney disease progression. Int Urol Nephrol. 2023 Apr;55(4):913-928. doi: 10.1007/s11255-022-03354-7

15. Mahendran KB, Bhaskar MV, Santha K, Inmozhi R, Perumal KK. Plasma and Urinary Type IV Collagen Levels for Early Detection of Nephropathy in Type 2 Diabetes Mellitus Patients. Int J Health Sci (Qassim). 2016 Oct;10(4):492-498. PMID: 27833513; PMCID: PMC50853
16. Uwaezuoke SN. The role of novel biomarkers in predicting diabetic nephropathy: a review. Int J Nephrol Renovasc Dis. 2017 Aug 17;10:221-231. doi: 10.2147/IJNRD.S143186.

17. Claudia G a, Sara N. de O.C., Sabrina R. G. and Jackson de S.M. Urinary Transferrin as a Marker of Renal Injury in Diabetic Individuals: An Integrative Review.Journal of Advances in Medicine and Medical Research Volume 36, Issue 6, Page 141-152, 2024; DOI: 10.9734/jammr/2024/v36i65459

18. Li B, Wang J, Ye W. A meta-analysis of urinary transferrin for early diagnosis of diabetic nephropathy. Lab Med. 2024 Jul 3;55(4):413-419. doi: 10.1093/labmed/lmad115

19. A P, C VK, Kalra P. Urinary transferrin as early marker of renal damage in type II diabetes mellitus: A case–control study [Internet]. Int J Clin Biochem Res. 2021 [cited 2025 Sep 16];8(1):33-39. Available from: https://doi.org/10.18231/j.ijcbr.2021.008

20. Tanaka T, Doi K, Maeda-Mamiya R, Negishi K, Portilla D, Sugaya T, Fujita T, Noiri E. Urinary L-type fatty acid-binding protein can reflect renal tubulointerstitial injury. Am J Pathol. 2009 Apr;174(4):1203-11. doi: 10.2353/ajpath.2009.080511. Epub 2009 Mar 5.

21. Kamijo-Ikemori A, Sugaya T, Yasuda T, Kawata T, Ota A, Tatsunami S, Kaise R, Ishimitsu T, Tanaka Y, Kimura K. Clinical significance of urinary liver-type fatty acid-binding protein in diabetic nephropathy of type 2 diabetic patients. Diabetes Care. 2011 Mar;34(3):691-6. doi: 10.2337/dc10-1392. Epub 2011 Jan 27

22. Zhang L, Xue S, Wu M, Dong D. Performance of urinary liver-type fatty acid-binding protein in diabetic nephropathy: A meta-analysis. Front Med (Lausanne). 2022 Sep 2;9:914587. doi: 10.3389/fmed.2022.914587.

23. Terzic B, Stanojevic I, Radojicic Z, Resan M, Petrovic D, Maksic Dj et al.; Urinary transferrin as an early biomarker of diabetic nephropathy: Vojnosanit pregled 2019; 76(6): 616-9; DOI: https://doi.org/10.2298/VSP170808138T

24. Chawla A, Chawla R, Jaggi S. Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum? Indian J Endocrinol Metab. 2016 Jul-Aug;20(4):546-51. doi: 10.4103/2230-8210.183480.

25. Rico-Fontalvo J, Aroca-Martínez G, Daza-Arnedo R, Cabrales J, Rodríguez-Yanez T, Cardona-Blanco M et al. Novel Biomarkers of Diabetic Kidney Disease. Biomolecules. 2023 Mar 31;13(4):633. doi: 10.3390/biom13040633.

26. Jha R, Lopez-Trevino S, Kankanamalage HR, Jha JC. Diabetes and Renal Complications: An Overview on Pathophysiology, Biomarkers and Therapeutic Interventions. Biomedicines. 2024 May 15;12(5):1098. doi: 10.3390/biomedicines12051098.

27. Chen C, Wang C, Hu C, Han Y, Zhao L, Zhu X, Xiao L, Sun L. Normoalbuminuric diabetic kidney disease. Front Med. 2017 Sep;11(3):310-318. doi: 10.1007/s11684-017-0542-7. Epub 2017 Jul 18.


28. Yamanouchi M, Furuichi K, Hoshino J, Ubara Y, Wada T. Nonproteinuric diabetic kidney disease. Clin Exp Nephrol. 2020 Jul;24(7):573-581. doi: 10.1007/s10157-020-01881-0. Epub 2020 Mar 31.

29. Wang C, Li C, Gong W, Lou T. New urinary biomarkers for diabetic kidney disease. Biomark Res. 2013 Feb 4;1(1):9. doi: 10.1186/2050-7771-1-9.

30. Tomino Y, Suzuki S, Azushima C, Shou I, Iijima T, Yagame M, Wang LN, Chen HC, Lai KN, Tan SY, Kim MJ. Asian multicenter trials on urinary type IV collagen in patients with diabetic nephropathy. J Clin Lab Anal. 2001;15(4):188-92. doi: 10.1002/jcla.1026.

31. Hassan, Marwa E.; Mahfouz, Mohamed H.; and Shoman, Mohamed S. (2020) "Assessment of urinary type IV collagen, alpha-1 microglobulin, and transferrin in type 2 diabetes mellitus with nephropathy," Journal of Medicine in Scientific Research: Vol. 3: Iss. 1, Article 4. DOI: https://doi.org/10.4103/JMISR.JMISR_74_19

32. Claudia Gusmão, Sara Nállia de Oliveira Costa, Sabrina Ribeiro Gonsalez, and Jackson de Souza-Menezes. 2024. “Urinary Transferrin As a Marker of Renal Injury in Diabetic Individuals: An Integrative Review”. Journal of Advances in Medicine and Medical Research 36 (6):141–152. https://doi.org/10.9734/jammr/2024/ v36i65459

33. Narita T, Hosoba M, Kakei M, Ito S. Increased urinary excretions of immunoglobulin g, ceruloplasmin, and transferrin predict development of microalbuminuria in patients with type 2 diabetes. Diabetes Care. 2006 Jan;29(1):142-4. doi: 10.2337/diacare.29.1.142.

34. Bangjian Li, Jieying Wang, Wen Ye, A meta-analysis of urinary transferrin for early diagnosis of diabetic nephropathy, Laboratory Medicine, Volume 55, Issue 4, July 2024, Pages 413–419, https://doi.org/10.1093/labmed/lmad115

35. Viswanathan V, Sivakumar S, Sekar V, Umapathy D, Kumpatla S. Clinical significance of urinary liver-type fatty acid binding protein at various stages of nephropathy. Indian J Nephrol. 2015 Sep-Oct;25(5):269-73. doi: 10.4103/0971-4065.145097.

36. Thi TND, Gia BN, Thi HLL, Thi TNC, Thanh HP. Evaluation of urinary L-FABP as an early marker for diabetic nephropathy in type 2 diabetic patients. J Med Biochem. 2020 Jan 23;39(2):224-230. doi: 10.2478/jomb-2019-0037.

37. Panduru NM, Forsblom C, Saraheimo M, Thorn L, Bierhaus A, Humpert PM, Groop PH; FinnDiane Study Group. Urinary liver-type fatty acid-binding protein and progression of diabetic nephropathy in type 1 diabetes. Diabetes Care. 2013 Jul;36(7):2077-83. doi: 10.2337/dc12-1868. Epub 2013 Feb 1.
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2025/12/13
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