Deneysel Diyabetik Nefropatide Böbrek Hasarının Değerlendirilmesinde Histopatolojik Skorlama Sistemleri

Öz

Diyabetik nefropati (DN) diyabetin en sık görülen mikrovasküler komplikasyonlarından biridir ve son dönem böbrek yetmezliğine yol açan nedenlerin başında gelmektedir. Günümüzde DN, dünya çapında diyabetli önemli sayıda kişiyi etkilemektedir ve kronik böbrek hastalığı olan hastaların yaklaşık üçte birini oluşturmaktadır. Bu nedenle DN gelişiminin mümkün olan en erken dönemde tanınması, gerekli tedavilerle hastalığın önlenmesi ya da gelişiminin yavaşlatılması son derece önemlidir. DN’nin histopatolojik değerlendirilmesi, hastalığın evrelerini belirleyerek doğru tedavi yaklaşımının uygulanabilmesi açısından son derece önemlidir. DN’nin erken dönemde glomerül ve tübül bazal membranlarının kalınlaşması, glomerül mezangiumunda ekstrasellüler matriks elemanlarının birikmesi, glomerül ve tübül epitellerinde hipertrofi ile ilgili yapısal değişimleri içerdiği açıklanmıştır. DN’nin anlaşılabilmesi için, gözlenen patolojik değişikliklerin puanlanarak semikantitatif veya kantitatif verilere dönüştürülerek istatiksel analiz yapılması oldukça önemlidir. Fakat farklı hayvan türlerinin ve farklı deneysel DN modellerinin varlığı, bu skorlama yöntemlerinde karışıklığa neden olmaktadır. Bu nedenle, DN deneysel modelleri için kullanılan histopatolojik skorlama sistemleri, son on yılda PubMed veritabanında yürütülen çalışmalarda ayrıntılı olarak incelenmiştir. Bu makalenin amacı, deneysel DN hayvan modellerinde gözlenen böbrek doku hasarını değerlendirmek için kullanılan farklı parametreler ve skorlama sistemlerine ilişkin kapsamlı bir kılavuz sunmaktır.

Anahtar Kelimeler

• Diyabetik nefropati
• Histopatoloji
• Böbrek
• Skor

Destekleyen Kurum

BEUN Bilimsel Araştırma Projeleri (Proje No: 2023-98210206-05) tarafından desteklenmiştir.

Proje Numarası

BEUN BAP Proje No: 2023-98210206-05

Etik Beyan

Derleme türünde bir çalışma olduğu için etik kurul oluru gerekmemiştir.

Teşekkür

Bu derlemenin hazırlanma sürecinde katkı ve değerlendirmeleriyle çalışmamızın gelişimine destek olan sayın editör ve hakemlerimize teşekkür ederiz.

Histopathological Scoring Systems in the Assessment of Renal Damage in Experimental Diabetic Nephropathy

Öz

Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes and a leading cause of end-stage renal failure. Currently, DN affects a significant number of people with diabetes worldwide and accounts for approximately one-third of patients with chronic kidney disease. Therefore, early diagnosis of DN is crucial for preventing or slowing its progression through appropriate treatment. Histopathological evaluation of DN is extremely important for determining the stages of the disease and applying the correct treatment approach. Early stages of DN are characterized by thickening of the glomerular and tubular basement membranes, accumulation of extracellular matrix elements in the glomerular mesangium, and structural changes related to hypertrophy in the glomerular and tubular epithelia. Understanding DN requires statistical analysis by scoring the observed pathological changes and converting them into semi-quantitative or quantitative data. However, the existence of different animal species and different experimental DN models leads to confusion in these scoring methods. Therefore, histopathological scoring systems used for experimental DN models have been examined in detail in studies conducted in the PubMed database over the last decade. The aim of this article is to provide a comprehensive guide to the different parameters and scoring systems used to assess kidney tissue damage observed in experimental DN animal models.

Anahtar Kelimeler

• Diabetic nephropathy
• Histopathology
• Kidney
• Score

Destekleyen Kurum

This project was supported by BEUN Scientific Research Projects (Project No: 2023-98210206-05).

Proje Numarası

BEUN BAP Proje No: 2023-98210206-05

Etik Beyan

Since this is a review study, ethical committee approval was not required.

Teşekkür

We would like to thank our esteemed editors and reviewers for their contributions and evaluations during the preparation of this compilation, which supported the development of our work.

Kaynakça

1. 1. Pelle MC, Provenzano M, Busutti M, Porcu CV, Zaffina I, Stanga L, Arturi F. Update on diabetic nephropathy. Life.2022;12(8):1202. doi:10.3390/life12081202
2. 2. Kalaçay D, Hacışevki A. The emerging roles of microRNAs as biomarkers in diabetic nephropathy. Turk J Diab Obes. 2022;6(3):287-295. doi: 10.25048/tudod.1111845
3. 3. Duan S, Lu F, Song D, Zhang C, Zhang B, Xing C, Yuan Y. Current challenges and future perspectives of renal tubular dysfunction in diabetic kidney disease. Front Endocrinol. 2021;12. doi:10.3389/fendo.2021.661185
4. 4. Ergenç M, Özenoğlu S, Turan İ, Özaçmak, VH, Özaçmak, HS. Diyabetik sıçanlarda melatonin uygulamasının karaciğer, böbrek, mide, pankreas ve göz dokularında oksidatif stres üzerine etkisi. Turk J Diab Obes. 2017;1(3):117-123. doi: 10.25048/ tjdo.2017.19
5. 5. Fakı S, Tam AA., İnce N, Altay FP, Karaahmetli G, Housseın M, Topaloğlu O, Ersoy R, Çakır B. Relationship between triglyceride-glucose index and microvascular complications in hospitalized patients with type 2 diabetes mellitus. Turk J Diab Obes. 2024; 8(1):13-18. doi: 10.25048/tudod.1359840
6. 6. Yılmaz MT, Bayraktaroğlu T, Kutlutürk F, Karadeniz Ş, Sargın M. Microalbuminuria prevalence in Turkish type 2 diabetics without known albuminuria: Results of the Developing Education on Microalbuminuria for Awareness of Renal and Cardiovascular Risks in Diabetes study-DEMAND-Turkey. Turk J Diab Obes. 2017;1(2):77-86. doi: 10.25048/tjdo.2017.12
7. 7. Karataş S, Köse Ş, Hacıoğlu Y. Vitamin D deficiency and microalbuminuria in patients with diabetes mellitus. Turk J Diab Obes. 2021;5(3):266-269. doi: 10.25048/tudod.942751.
8. 8. Umanath K, Lewis JB. Update on diabetic nephropathy: Core curriculum. Am J Kidney Dis. 2018;71(6):884-895. doi:10.1053/j.ajkd.2017.10.026

9. 9. Tucker BJ, Collins RC, Ziegler MG, Blandz RÇ. Glomerular hyperfiltration and extracellular volume in diabetic rats. Kidney Int. 1991;39:1176-1183. doi: 10.1038/ki.1991.149.
10. 10. Fakı S, İnce N, Tam AA, Altay FP, Karaahmetli G, Erdoğan BT, Çuhacı Seyrek N, Topaloğlu O, Ersoy R, Çakır B. The relationship between ABO and Rh blood groups and microvascular complications of diabetes in patients with type 2 diabetes mellitus. Turk J Diab Obes. 2024;8(1):65-70. doi:10.25048/tudod.1359676
11. 11. Tunçdemir M, Öztürk M. Deneysel diyabetik nefropatide anjiyotensin II reseptör blokerlerinin podosit hasarı ve glomerüler apoptoz üzerine etkileri [Bildiri]. 2010;ACTHIS-50469, 7 sayfa.
12. 12. Eroğlu CE, Toksöz DY, Balimre BÇ, Şengül E, Yılmaz Z. Akut böbrek hasarı olgusunda metformin ile ilişkili laktik asidoz. Turk J Diab Obes. 2021;5(2):233-236. doi:10.25048/tudod.868292
13. 13. Tervaert TW, Mooyaart AL, Amann K, Cohen AH, Cook HT, Drachenberg CB, Bajema I M. Diabetic nephropathy: Pathologic classification. J Am Soc Nephrol. 2010;21(4):556-563. doi:10.1681/ASN.2010010080
14. 14. Perrin NE, Torbjörnsdotter TB, Jaremko GA, Berg UB. Tip 1 diyabetli normoalbuminürik hastalarda böbrek biyopsilerinin takibi. Pediatr Nephrol. 2004;19(10):1004-1013. doi:10.1007/ s00467-004-1509-x
15. 15. Drummond K, Mauer M; Uluslararası Diyabetik Nefropati Çalışma Grubu. Early natural history of nephropathy in type 1 diabetes: II. Early structural changes in type 1 diabetic kidneys. Diabetes. 2002;51(5):1580-1587. doi:10.2337/diabetes.51.5.1580
16. 16. Falk RJ, Scheinman JI, Mauer SM, Michael AF. Polyclonal expansion of basement membrane components in diabetic nephropathy. Diabetes. 1983;32(Suppl.2):34-39. doi: 10.2337/ diab.32.2.s34
17. 17. Kim Y, Kleppel MM, Butkowski R, Mauer SM, Wieslander J, Michael AF. Differential expression of basement membrane collagen chains in diabetic nephropathy. Am J Pathol.1991;138(2):413-420.
18. 18. Zhao YH, Fan YJ. Resveratrol improves lipid metabolism in rats with diabetic nephropathy. Front Biosci (Landmark Ed).2020;25(10):1913-1924. doi:10.2741/4885
19. 19. Giralt-López A, Molina-Van den Bosch M, Vergara A, García-Carro C, Seron D, Jacobs-Cachá C, Soler MJ. Revisiting experimental models of diabetic nephropathy. Int J Mol Sci.2020;21(10): 3587. doi: 10.3390/ijms21103587
20. 20. Mayoral LP, Andrade GM, Mayoral EP, Huerta TH, Canseco SP, Rodal Canales FJ, Cabrera-Fuentes HA, Cruz MM, Pérez Santiago AD, Alpuche JJ, Zenteno E, Ruíz HM, Cruz RM, Jeronimo JH, Perez-Campos E. Obesity subtypes, associated biomarkers, and heterogeneity. Indian J Med Res. 2020;151(1):11-21. doi:10.4103/ijmr.IJMR_1768_17
21. 21. Wiggins RC. The podocytopathy spectrum: A unifying view of glomerular diseases. Kidney Int. 2007;71(12):1205-1214. doi: 10.1038/sj.ki.5002222
22. 22. Haraldsson B, Nyström J, Deen WM. Properties of the glomerular barrier and mechanisms of proteinuria. Physiol Rev.2008;88(2):451-487. doi: 10.1152/physrev.00055.2006
23. 23. Scott RP, Quaggin SE. Review series: The cell biology of kidney filtration. J Cell Biol. 2015;209(2):199-210. doi:10.1083/ jcb.201410017
24. 24. White KE. Investigating the structure of the renal glomerulus - making it matter. Micron. 2012;43(10):1001-1009. doi:10.1016/j.micron.2012.04.013
25. 25. Panesso MC, Shi M, Cho HJ, Paek J, Ye J, Moe OW, Hu MC. Klotho has dual protective effects on cisplatin-induced acute kidney injury. Kidney Int. 2014;85(4):855-870. doi:10.1038/ ki.2013.489
26. 26. He Y, Chen X, Yu Z, Wu D, Lv Y, Shi S, Zhu H. Sodium dicarboxylate cotransporter-1 expression in renal tissues and its role in rat experimental nephrolithiasis. J Nephrol. 2004; 17(1):34-42. doi:10.1093/joneph/17.1.34
27. 27. Kim AJ, Ro H, Kim H, Chang, JH, Lee HH, Chung W, Jung JY. Klotho and S100A8/A9 as discriminative markers between pre-renal and intrinsic acute kidney injury. PLOS ONE. 2016;11(1). doi:10.1371/journal.pone.0147255
28. 28. Pranoto IW, Djojodimedjo T, Soebadi MA, Rahaju AS. (n.d.). Effects of iodinated contrast agents on renal iNOS expression and tubular histopathological changes. Narra J. 2024;4(3). doi:10.52225/narra.v4i3.1227
29. 29. Aksu F, Aksu B, Unlu N, Karaca T, Ayvaz S, Erman H, Uzun H, Keles N, Bulur S, Unlu E. Antioxidant and renoprotective effects of sphingosylphosphorylcholine in contrast-induced nephropathy in rats. Ren Fail. 2016;38(7):1089-1098. doi: 10.1080/0886022X.2016.1206826
30. 30. Iyoda M, Shibata T, Hirai Y, Kuno Y, Akizawa T. Nilotinib reduces kidney injury and prolongs survival in chronic kidney disease. JASN. 2011;22(8):1486-1496. doi:10.1681/ ASN.2010111158
31. 31. Kuno Y, Iyoda M, Shibata T, Hirai Y, Akizawa T. The phosphodiesterase type 5 inhibitor sildenafil ameliorates diabetic nephropathy in insulin-independent Otsuka Long-Evans Tokushima fatty rats. Br J Pharmacol. 2011;162(6):1389-1400. doi:10.1111/j.1476-5381.2010.01149.x
32. 32. El-Kady MM, Naggar RA, Guimei M, Talaat IM, Shaker OG, Saber-Ayad M. Early renoprotective effect of ruxolitinib in a rat model of diabetic nephropathy. Pharmaceuticals (Basel). 2021;14(7):608. doi:10.3390/ph14070608
33. 33. Fareed SA, Yousef EM, Abd El-Moneam SM. Assessment of effects of rosemary essential oil on the kidney pathology of diabetic adult male albino rats. Cureus. 2023;15(3). doi:10.7759/ cureus.35736
34. 34. Hou J, Yan G, Liu B, Zhu B, Qiao, Y, Wang D, Li R, Luo E, Tang C. Protective effects of enalapril maleate and folic acid tablets against contrast-induced nephropathy in diabetic rats. Biomed Res Int. 2018. doi: 10.1155/2018/4609750
35. 35. Ahmad A, Mondello S, Di Paola R, Mazzon E, Esposito E, Catania MA, Italiano D, Mondello P, Aloisi C, Cuzzocrea S. Protective effect of apocynin, a NADPH-oxidase inhibitor, against contrast-induced nephropathy in diabetic rats: A comparison with N-acetylcysteine. Eur J Pharmacol. 2012;674:397-406. doi:10.1016/j.ejphar.2011.11.062
36. 36. Deng J, Wu G, Yang C, Li Y, Jing Q, Han Y. Rosuvastatin ameliorates contrast-induced nephropathy in diabetic male rats via modulation of nitric oxide, inflammatory responses, oxidative stress, and apoptosis. J Tranl Med. 2015;13:53. doi:10.1186/ s12967-015-0416-1
37. 37. Shaban AM, Raslan M, Qahl SH, Elsayed K, Abdelhameed MS, Oyouni AAA, Al-Amer, OM, Hammouda O, El-Magd MA. Therapeutic effects of camel milk and its exosomes on diabetic nephropathy in rats. Membranes. 2022;12(11):1060. doi:10.3390/membranes12111060
38. 38. Chang CL, Sung PH, Chen KH, Shao PL, Yang CC, Cheng BC, Lin KC, Chen CH, Chai HT, Chang HW, Yip HK, Chen HH. Adipose-derived mesenchymal stem cell-derived exosomes attenuate excessive systemic inflammatory response, reduce organ injury, and improve outcomes in a rat sepsis model. Am J Transl Res. 2018;10:1053-1070. doi.org/10.5114/ fn.2023.130455
39. 39. Kuno Y, Iyoda M, Shibata T, Hirai Y, Akizawa T. The phosphodiesterase type 5 inhibitor sildenafil ameliorates diabetic nephropathy in insulin-independent Otsuka Long-Evans Tokushima fatty rats. Br J Pharmacol. 2011;162(6):1389-1400. doi:10.1111/j.1476-5381.2010.01149.x
40. 40. Iyoda M, Shibata T, Hirai Y, Kuno Y, Akizawa T. Nilotinib reduces kidney injury and prolongs survival in chronic kidney disease. JASN. 2011;22(8):1486-1496. doi:10.1681/ ASN.2010111158
41. 41. Chen H, Ren J, Loo WTY, Hao L, Wang M. Lysyl oxidase expression and histopathological changes in diabetic rat nephrons. Mol Med Rep. 2018;17(2):2431-2441. doi:10.3892/ mmr.2017.8182