ISSN: 2706-8870
Volume 9, Number 3 (2024)
Year Launched: 2016
Journal Menu
■ About The Journal
■ Aims & Scope
■ Editorial Board
■ Article Processing Charge
■ Archive

The role of adhesion molecule expression in the development of morphological changes in renal tissue in patients with type 2 diabetes

Volume 9, Issue 3, June 2024     |     PP. 91-115      |     PDF (368 K)    |     Pub. Date: August 31, 2024
DOI: 10.54647/cm321287    32 Downloads     2602 Views  

Author(s)

T.S. Ryabova, S.M. Kirov Military Medical Academy, Department of Nephrology and Efferent Therapy, 194044, Saint Petersburg, st. Academician Lebedeva, 6, Russia
I.A. Rakityanskaya, Department of Allergology, Immunology and Clinical Transfusiology, Municipal Outpatient Hospital no. 112, 195427, Saint Petersburg, st. Academician Baykova, 25/1, Russia

Abstract
Research objective. The work is devoted to studying the role of the expression of intercellular adhesion molecules-1 (ICAM-1, CD54), P-selectin (CD62P) and E-selectin (CD62E) in renal tissue in the development and progression of morphological changes in diabetic nephropathy in patients with type 2 diabetes mellitus.
Material and methods. The examination was carried out in 50 patients with type 2 diabetes mellitus (T2DM) (average age 66.58±3.27 years). The duration of diabetes was 14.744±0.1.062 years. All patients underwent intravital puncture biopsy of the kidney. To confirm the morphological diagnosis, light and immunofluorescence microscopy of kidney tissue biopsies were performed. Morphological changes in tissue were assessed in accordance with the latest international classification of diabetic nephropathy, developed in 2010. According to light microscopy, class IIa (mild mesangial expansion) was identified in 12 patients, class IIb (severe mesangial expansion) was identified in 14 patients, in 19 patients – class III (nodular Kimmelstiel-Wilson lesions) and in 5 patients – class IV (advanced diabetic glomerulosclerosis).
The expression of ICAM-1, P- and E-selectin was determined using monoclonal antibodies, FITC anti-human CD54 Antibody, FITC anti-human CD62P Antibody, FITC anti-human CD62E Antibody (USA). The intensity of expression in points (0–4), the nature and location of the expression of adhesion molecules in the glomerular endothelium and in peritubular capillaries were assessed.
Results. To identify the prognostic significance of the expression of CD54, CD62R and CD62E in the progression of morphological changes in tissue during the development of DN, correlation analysis and linear regression analysis were performed. The findings demonstrated the role of adhesion molecule expression in the development of mesangial matrix expansion, basement membrane thickening, arteriolar hyplinosis, and tubulointerstitial lesions. The development of morphological changes in tissue is also confirmed by the regression model between the expression of adhesion molecules in tissue with the progression of the stage of DN.
Conclusion. We conducted a statistical analysis to explore how the expression of adhesion molecules affects the changes in kidney tissue. This analysis confirmed the previously suggested idea that interstitial damage plays a crucial role in the progression of DKD. One of the main mechanisms contributing to the development of interstitial fibrosis is the expression of certain adhesion molecules, such as ICAM-1, CD62P, and CD62E

Keywords
Type 2 Diabetes Mellitus, Diabetic Kidney Disease, Renal Biopsy, ICAM-1, P-selectin, E-selectin

Cite this paper
T.S. Ryabova, I.A. Rakityanskaya, The role of adhesion molecule expression in the development of morphological changes in renal tissue in patients with type 2 diabetes , SCIREA Journal of Clinical Medicine. Volume 9, Issue 3, June 2024 | PP. 91-115. 10.54647/cm321287

References

[ 1 ] GBD 2021 Diabetes Collaborators . Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: A systematic analysis for the Global Burden of Disease Study 2021. Lancet (2023) 402:203–34. doi: 10.1016/S0140-6736(23)01301-6
[ 2 ] Selby N.M., Selby N.M., Taal M.W. An updated overview of diabetic nephropathy: Diagnosis, prognosis, treatment goals and latest guidelines // Diabetes Obes. Metab. 2020; 22(1): 3-15. doi: 10.1111/dom.14007.
[ 3 ] Alicic R.Z., Rooney M.T., Tuttle K.R. Diabetic Kidney Disease: Challenges, Progress, and Possibilities. Clin J Am Soc Nephrol. 2017 Dec 7;12(12):2032-2045. doi: 10.2215/CJN.11491116.
[ 4 ] Gheith Osama , Farouk Nashwa , Nampoory Narayanan , Medhat A Halim, Torki Al-Otaibi. Diabetic kidney disease: world wide difference of prevalence and risk factors J Nephropharmacol. 2015 Oct 9;5(1):49-56. eCollection 2016.
[ 5 ] Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, Stein C, Basit A, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022 Jan;183:109119. doi: 10.1016/j.diabres.2021.109119
[ 6 ] Chengren Xu, Xiaowen Ha, Shufen Yang, Xuefei Tian, Hong Jian. Advances in understanding and treating diabetic kidney disease: focus on tubulointerstitial inflammation mechanisms Front Endocrinol (Lausanne). 2023; 14: 1232790. doi: 10.3389/fendo.2023.1232790
[ 7 ] Levin A., Rocco M., Eknoyan G., Levin N., Becker B., Blake P.G, et al. . KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. Am J Kidney Dis (2007) 49:S12–S154. doi: 10.1053/j.ajkd.2006.12.005
[ 8 ] Tervaert T.W.C., Mooyaart A.L., Amann K., Cohen A.H., Cook H.T., Drachenberg CB, et al.. Pathologic classification of diabetic nephropathy. J Am Soc Nephrol (2010) 21:556–63. doi: 10.1681/ASN.2010010010
[ 9 ] Zeni L., Norden A.G.W., Cancarini G., Unwin R.J. A more tubulocentric view of diabetic kidney disease. J Nephrol (2017) 30:701–17. doi: 10.1007/s40620-017-0423-9,
[ 10 ] Gilbert Richard E. Proximal Tubulopathy: Prime Mover and Key Therapeutic Target in Diabetic Kidney Disease. Diabetes . 2017 Apr;66(4):791-800. doi: 10.2337/db16-0796
[ 11 ] Klessens C.Q.F., Woutman T.D., Veraar K.A.M., Zandbergen M., Valk E.J.J., Rotmans J.I., et al.. An autopsy study suggests that diabetic nephropathy is underdiagnosed. Kidney Int (2016) 90:149–56. doi: 10.1016/j.kint.2016.01.023
[ 12 ] Martínez-Castelao A., Navarro-González J., Górriz J., De Alvaro F. The concept and the epidemiology of diabetic nephropathy have changed in recent years. JCM (2015) 4:1207–16. doi: 10.3390/jcm4061207,
[ 13 ] Tuttle K.R., Bakris G.L., Bilous R.W., Chiang J.L., De Boer I.H., Goldstein-Fuchs J, et al.. Diabetic kidney disease: A report from an ADA consensus conference. Am J Kidney Dis (2014) 64:510–33. doi: 10.1053/j.ajkd.2014.08.001
[ 14 ] White K.E., Marshall S.M., Bilous R.W. Prevalence of atubular glomeruli in type 2 diabetic patients with nephropathy. Nephrol Dial Transplant  2008 Nov;23(11):3539-45. doi: 10.1093/ndt/gfn351.
[ 15 ] Chevalier R.L., Forbes M.S. Generation and evolution of atubular glomeruli in the progression of renal disorders. J Am Soc Nephrol. 2008 Feb;19(2):197-206. doi: 10.1681/ASN.2007080862..
[ 16 ] Steffes M.W., Osterby R., Chavers B., Mauer S.M: Mesangial expansion as a central mechanism for loss of kidney function in diabetic patients. Diabetes 1989 Sep;38(9):1077-81. doi: 10.2337/diab.38.9.1077.
[ 17 ] Zimmerman K. Über den bau des glomerulus der säugerniere. Weitere mittleillungen. Z Mikrosk Anat Forsch. 1933;32:176–278
[ 18 ] Kimmelstiel P., Wilson C. Intercapillary lesions in the glomeruli of the kidney. Am J Pathol. 1936;12(1):83–98
[ 19 ] Davies M. The mesangial cell: A tissue culture view. Kidney Int. 1994;45(2):320–7. doi: 10.1038/ki.1994.41
[ 20 ] Sakai F., Kriz W. The structural relationship between mesangial cells and basement membrane of the renal glomerulus. Anat Embryol. 1987;176(3):373–86. doi: 10.1007/BF00310191
[ 21 ] Nangaku M. Mechanisms of tubulointerstitial injury in the kidney: final common pathways to end-stage renal failure. Intern. Med. 2004; Jan;43(1):9-17. doi: 10.2169/internalmedicine.43.9.
[ 22 ] Zavadil J., Bottinger E.P. TGF-βand epithelial-to-mesenchymal transitions. Oncogene 2005 Aug 29;24(37):5764-74. doi: 10.1038/sj.onc.1208927.
[ 23 ] American Diabetes Association . Diagnosis and classification of diabetes mellitus. Diabetes Care 2014; 37(1):S81–90. doi: 10.2337/dc14-S081
[ 24 ] Raimund Pichler, Maryam Afkarian, Brad P. Dieter, Katherine R. Tuttle. Immunity and inflammation in diabetic kidney disease: translating mechanisms to biomarkers and treatment targets. Am J Physiol Renal Physiol. 2017; Apr 1;312(4):F716-F731. doi: 10.1152/ajprenal.00314.2016
[ 25 ] Blum A., Pastukh N., Socea D., Jabaly H. Levels of adhesion molecules in peripheral blood correlat with stages of diabetic retinopathy and may serve as bio markers for microvascular complications. Cytokine 2018; 106:76–9. doi: 10.1016/j.cyto.2017.10.014,
[ 26 ] Liu J.J., Yeoh L.Y., Sum C.F., Tavintharan S., Ng XW, Liu S, et al.. Vascular cell adhesion molecule-1, but not intercellular adhesion molecule-1, is associated with diabetic kidney disease in asians with type 2 diabetes. J Diabetes Complications 2015; 29:707–12. doi: 10.1016/j.jdiacomp.2015.02.011
[ 27 ] Solez K., Colvin R.B., Racusen L.C,. Haas M., Sis B., Mengel M., et al. Banff 07 classification of renal allograft pathology: Updates and future directions. Am J Transplant 2008; 8(4):753-60. doi: 10.1111/j.1600-6143
[ 28 ] Gellman D.D., Pirani C.L., Soothill J.F., Muehrcke R.C., Kark R.M. Diabetic nephropathy: A clinical and pathologic study based on renal biopsies. Medicine (Baltimore) 1959 Dec:38:321-67.
[ 29 ] Gambara V., Mecca G., Remuzzi G., Bertani T: Heterogeneous nature of renal lesions in type II diabetes. J Am Soc Nephrol 1993; Feb;3(8):1458-66. doi: 10.1681/ASN.V381458.
[ 30 ] Fioretto P., Mauer M., Brocco E., Velussi M., Frigato F., Muollo B., et al: Patterns of renal injury in NIDDM patients with microalbuminuria. Diabetologia 1996; Dec;39(12):1569-76. doi: 10.1007/s001250050616.
[ 31 ] Osterby R., Gall M.A., Schmitz A., Nielsen F.S., Nyberg G., Parving H.H: Glomerular structure and function in proteinuric type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993; Oct;36(10):1064-70. doi: 10.1007/BF02374500.
[ 32 ] White K.E., Bilous R.W.: Type 2 diabetic patients with nephropathy show structural-functional relationships that are similar to type 1 disease. J Am Soc Nephrol 2000; Sep;11(9):1667-1673. doi: 10.1681/ASN.V1191667.
[ 33 ] Perrin N.E., Torbjornsdotter T.B., Jaremko G.A., Berg U.B.: The course of diabetic glomerulopathy in patients with type I diabetes: A 6-year follow-up with serial biopsies. Kidney Int 2006; Feb;69(4):699-705. doi: 10.1038/sj.ki.5000146.
[ 34 ] Haas M. Alport syndrome and thin glomerular basement membrane nephropathy: A practical approach to diagnosis. Arch Pathol Lab Med 2009; Feb;133(2):224-32. doi: 10.5858/133.2.224.
[ 35 ] Stout L.C., Kumar S., Whorton E.B. Focal mesangiolysis and the pathogenesis of the Kimmelstiel–Wilson nodule. Hum Pathol 1993; Jan;24(1):77-89. doi: 10.1016/0046-8177(93)90066-p.
[ 36 ] Hong D., Zheng T., Jia-qing S., Jian W., Zhi-hong L., Lei-shi L: Nodular glomerular lesion: A later stage of diabetic nephropathy? Diabetes Res Clin Pract. 2007; Nov;78(2):189-95. doi: 10.1016/j.diabres.2007.03.024.
[ 37 ] Qian Y., Feldman E., Pennathur S., et al. From fibrosis to sclerosis: Mechanisms of glomerulosclerosis in diabetic nephropathy. Diabetes 2008; Jun;57(6):1439-45. doi: 10.2337/db08-0061.
[ 38 ] Allen A: So-called intercapillary glomerulosclerosis: A lesion associated with diabetes mellitus. Morphogenesis and significance. Arch Path 32: 33–51, 1941
[ 39 ] Najafian B., Kim Y., Crosson J.T., et al. Atubular glomeruli and glomerulotubular junction abnormalities in diabetic nephropathy. J Am Soc Nephrol 2003; 14: 908–917, doi: 10.1097/01.asn.0000057854.32413.81.
[ 40 ] Blum A., Pastukh N., Socea D., Jabaly H. Levels of adhesion molecules in peripheral blood correlat with stages of diabetic retinopathy and may serve as bio markers for microvascular complications. Cytokine 2018; 106:76–9. doi: 10.1016/j.cyto.2017.10.014
[ 41 ] Siddiqui Khalid, George Teena P., Mujammami Muhammad et al. The association of cell adhesion molecules and selectins (VCAM-1, ICAM-1, E-selectin, L-selectin, and P-selectin) with microvascular complications in patients with type 2 diabetes: A follow-up study. Front Endocrinol (Lausanne) 2023; Feb 9:14:1072288. doi: 10.3389/fendo.2023.1072288
[ 42 ] Lhotta K., Neumayer H.P, Joannidis M., Geissler, Königet P.. Renal expression of intercellular adhesion molecule-1 in different forms of glomerulonephritis. Clin Sci (Lond). 1991; Oct;81(4):477-81. doi: 10.1042/cs0810477.
[ 43 ] Fuggle S.V., Sanderson J.B., Gray D., Richardson W.A., Morriset P.J. . Variation in expression of endothelial adhesion molecules in pretransplant and transplanted kidneys—Correlation with intragraft events. Transplantation 1993; Jan;55(1):117-23. doi: 10.1097/00007890-199301000-00022.
[ 44 ] Nikolic-Paterson D.J., Lan H.Y., Hill P.A., Vannice J.L., Atkinset R.C. Suppression of experimental glomerulonephritis by the interleukin-1receptor antagonist: Inhibition of intercellular adhesion molecule-1 expression. JAm Soc Nephrol 1994; Mar;4(9):1695-700. doi: 10.1681/ASN.V491695.
[ 45 ] Sugimoto H., Shikata K., Hirata K., Akiyama K., Matsuda M., Kushiro M., et al. Increased expression of intercellular adhesion molecule-1 (ICAM-1) in diabetic rat glomeruli: glomerular hyperfiltration is a potential mechanism of ICAM-1 upregulation. Diabetes 1997; Dec;46(12):2075-81. doi: 10.2337/diab.46.12.2075.
[ 46 ] Roy-haudhury Prabir, Wu B.R., King G., Campbell M., Macleod A.M. et al.,. Adhesion molecule interactions in human glomerulonephritis: Importance of the tubulointerstitium. Kidney International 1996; Jan;49(1):127-34. doi: 10.1038/ki.1996.17.
[ 47 ] Omoto S., Nomura S., Shouzu A., Hayakawa T., Shimizu H., Miyake Y., et al.,. Significance of Platelet-Derived Microparticles and Activated Platelets in Diabetic Nephropathy. Nephron Exp. Nephrol. 1999;81:271–277. doi: 10.1159/000045292
[ 48 ] Hirata K., Shikata K., Matsuda M., Akiyama K., Sugimoto H., Kushiro M., et al.,. Increased expression of selectins in kidneys of patients with diabetic nephropathy. Diabetologia. 1998;41:185–192. doi: 10.1007/s001250050888
[ 49 ] Alicic R.Z., Rooney M.T., Tuttle K.R. Diabetic kidney disease: Challenges, progress, and possibilities. Clin J Am Soc Nephrol. 2017;12(12):2032–45. doi: 10.2215/CJN.11491116.