Diyabetik Nefropatide SCUBE-1 ve sCD40L Seviyelerinin İncelenmesi

Abstract

Amaç: Diyabetik nefropati ve aterosklerorik kalp hastalıkları arasında yakın bir ilişki mevcuttur. Biz de, ateroskleroz sürecinde rol oynadığı bilinen SCUBE-1 ve sCD40L’ın tip 2 diyabeti olan hastalarda, nefropatinin ilerlemesi ile birlikte nasıl değiştiğini araştırmayı amaçladık.

Gereç ve Yöntemler: Otuz sağlıklı kişi (grup 1) ve 74 tip 2 diyabeti olan hasta (normal albuminüri grubu (grup 2, n=33), orta derece artmış albuminüri grubu (grup 3, n=22) ve şiddetli derecede artmış albuminüri grubu (grup 4, n=19) olarak üç gruba ayrıldı) çalışmaya dahil edildi. Plazma SCUBE-1 ve sCD40L seviyeleri, enzim-bağlı immunosorbent analiz tekniği kullanılarak ölçüldü.

Bulgular: Ortalama SCUBE-1 seviyeleri grup 1 ve grup 2 ile karşılaştırıldığında, grup 4’te (sırasıyla p=0,005 ve p=0,014) ve grup 1 ve grup 2 ile karşılaştırıldığında grup 3’te (sırasıyla p=0,011 ve p=0,028) anlamlı olarak yüksekti. Ortalama sCD40L seviyeleri grup 4’te diğer üç gruptan (tüm p<0,001) ve grup 3’te ise grup 1 ve grup 2’den (sırasıyla p=0,001 ve p=0,016) anlamlı olarak yüksekti. Ayrıca SCUBE-1 seviyeleri total kolesterol seviyesi (r=0,220; p=0,025) ve trigliserit (r=0,194; p=0,049) ile pozitif yönlü koreleydi. Yanı sıra, sCD40L seviyesi ise sadece kreatinin seviyesi (r=0,297; p=0,002) ile pozitif yönlü koreleydi.

Sonuç: SCUBE-1 ve sCD40L seviyeleri tip 2 diyabette nefropatinin progresyonu ile artmaktadır. Bu artış SCUBE-1 ve sCD40L’ın diyabetik nefropatiye bağlı ateroskleroz sürecinde anahtar rol oynuyor olabileceğini ve diyabetik nefropatinin bu parametrelerin seviyelerini etkiliyor olabileceğini düşündürmektedir.

Keywords

• SCUBE-1,sCD40L,ateroskleroz,diyabetik nefropati

The Evaluation of SCUBE-1 and sCD40L Levels in Diabetic Nephropathy

Abstract

Aim: There is a close link between diabetic nephropathy and atherosclerotic heart disease. We aimed to evaluate the changes of SCUBE-1 and sCD40L, which play role in the course of atherosclerosis, with the progression of nephropathy in patients with type 2 diabetes.

Material and Methods: Thirty healthy subjects (group 1) and 74 patients with type 2 diabetes (divided into 3 groups as normal albuminuria group (group 2, n=33), moderately increased albuminuria group (group 3, n=22) and severely increased albuminuria group (group 4, n=19)) were enrolled in the study. Plasma SCUBE-1 and sCD40L levels were measured using the enzyme-linked immunosorbent assay technique.

Results: Mean SCUBE-1 levels were significantly higher in group 4 compared to group 1 and group 2 (p=0.005 and p=0.014, respectively) and in group 3 compared to group 1 and group 2 (p=0.011 and p=0.028, respectively). Mean sCD40L levels were significantly higher in group 4 than in other three groups (all p<0.001), and in group 3 than in group 1 and group 2 (p=0.001 and p=0.016, respectively). Furthermore, SCUBE-1 level was positively correlated with total cholesterol level (r=0.212, p=0.031) and triglyceride (r=0.194, p=0.049). Likewise, sCD40L level was positively correlated with only creatinine level (r=0.297, p=0.002).

Conclusion: SCUBE-1 and sCD40L levels increased with the progression of nephropathy in type 2 diabetes. This increment suggested that SCUBE-1 and sCD40L may play key role in the course of atherosclerosis due to diabetic nephropathy and, diabetic nephropathy may affect the levels of these parameters.

Keywords

• SCUBE-1,sCD40L,atherosclerosis,diabetic nephropathy

References

1. Navarro-González JF, Mora-Fernández C, Muros de Fuentes M, García-Pérez J. Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat Rev Nephrol. 2011;7(6):327-40.
2. Pálsson R, Patel UD. Cardiovascular complications of diabetic kidney disease. Adv Chronic Kidney Dis. 2014;21(3):273-80.
3. Ma RC. Genetics of cardiovascular and renal complications in diabetes. J Diabetes Investig. 2016;7(2):139-54.
4. Jakuszewski P, Czerwieńska B, Chudek J, Wiecek A. Which components of malnutrition-inflammation-atherosclerosis syndrome are more common in haemodialysis patients with diabetic nephropathy? Nephrology (Carlton). 2009;14(7):643-9.
5. Yang RB, Ng CK, Wasserman SM, Colman SD, Shenoy S, Mehraban F, et al. Identification of a novel family of cell-surface proteins expressed in human vascular endothelium. J Biol Chem. 2002;277(48):46364-73.
6. Tu CF, Su YH, Huang YN, Tsai MT, Li LT, Chen YL, et al. Localization and characterization of a novel secreted protein SCUBE1 in human platelets. Cardiovasc Res. 2006;71(3):486-95.
7. Tu CF, Yan YT, Wu SY, Djoko B, Tsai MT, Cheng CJ, et al. Domain and functional analysis of a novel platelet-endothelial cell surface protein, SCUBE1. J Biol Chem. 2008;283(18):12478-88.
8. Sonmez E, Turkdogan KA, Karabacak M, Civelek C, Yilmaz C, Ozer OF, et al. The diagnostic role of signal peptide-C1r/C1s, Uegf, and Bmp1-epidermal growth factor domain-containing protein 1 in non-ST-elevation acute coronary syndrome. Am J Emer Med. 2015;33(1):21-4.

9. Bolayır HA, Kıvrak T, Güneş H, Akaslan D, Şahin Ö, Bolayır A. The role of SCUBE1 in the development of late stent thrombosis presenting with ST-elevation myocardial infarction. Rev Port Cardiol. 2018;37(5):375-81.
10. Turkmen S, Eryigit U, Karaca Y, Mentese A, Sumer UA, Yulug E, et al. Diagnostic value of plasma signal peptide-Cub-Egf domain-containing protein-1 (SCUBE-1) in an experimental model of acute ischemic stroke. Am J Emerg Med. 2015;33(2):262-5.
11. Restituto P, Colina I, Varo JJ, Varo N. Adiponectin diminishes platelet aggregation and sCD40L release. Potential role in the metabolic syndrome. Am J Physiol Endocrinol Metab. 2010;298(5):E1072-7.
12. Schönbeck U, Libby P. CD40 signaling and plaque instability. Circ Res. 2001;89(12):1092-103.
13. Zhao W, Zhang F, Li Z, Yu H, Li Z, Gao W. Soluble CD40 ligand is associated with angiographic severity of coronary artery disease in patients with acute coronary syndrome. Chin Med J (Engl). 2014;127(12):2218-21.
14. Heeschen C, Dimmeler S, Hamm CW, van den Brand MJ, Boersma E, Zeiher AM, et al. Soluble CD40 ligand in acute coronary syndromes. N Engl J Med. 2003;348(12):1104-11.
15. Blake GJ, Ostfeld RJ, Yucel EK, Varo N, Schönbeck U, Blake MA, et al. Soluble CD40 ligand levels indicate lipid accumulation in carotid atheroma: an in vivo study with high-resolution MRI. Arterioscler Thromb Vasc Biol. 2003;23(1):e11-4.
16. Yan J, Wu Z, Huang Z, Li L, Zhong R, Kong X. Clinical implications of increased expression of CD40L in patients with acute coronary syndromes. Chin Med J (Engl). 2002;115(4):491-3.
17. Ulusoy S, Ozkan G, Menteşe A, Yavuz A, Karahan SC, Sümer AU. Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) level in hemodialysis patients and parameters affecting that level. Clin Biochem. 2012;45(16-17):1444-9.
18. Schwabe RF, Engelmann H, Hess S, Fricke H. Soluble CD40 in the serum of healthy donors, patients with chronic renal failure, haemodialysis and chronic ambulatory peritoneal dialysis (CAPD) patients. Clin Exp Immunol. 1999;117(1):153-8.
19. Desideri G, Panichi V, Paoletti S, Grassi D, Bigazzi R, Beati S, et al. Soluble CD40 ligand is predictive of combined cardiovascular morbidity and mortality in patients on haemodialysis at a relatively short-term follow-up. Nephrol Dial Transplant. 2011;26(9):2983-8.
20. Xie JX, Alderson H, Ritchie J, Kalra PA, Xie Y, Ren K, et al. Circulating CD40 and sCD40L predict changes in renal function in subjects with chronic kidney disease. Sci Rep. 2017;7:7942.
21. Dai DF, Thajeb P, Tu CF, Chiang FT, Chen CH, Yang RB, et al. Plasma concentration of SCUBE1, a novel platelet protein, is elevated in patients with acute coronary syndrome and ischemic stroke. J Am Coll Cardiol. 2008;51(22):2173-80.
22. Turkmen S, Mentese S, Mentese A, Sumer AU, Saglam K, Yulug E, et al. The value of signal peptide-CUB-EGF domain-containing protein 1 and oxidative stress parameters in the diagnosis of acute mesenteric ischemia. Acad Emerg Med. 2013;20(3):257-64.
23. Özkan G, Ulusoy S, Menteşe A, Karahan SC, Cansiz M. New marker of platelet activation, SCUBE1, is elevated in hypertensive patients. Am J Hypertens. 2013;26(6):748-53.
24. Icel E, Icel A, Mertoglu C, Tasli NG, Karakurt Y, Ucak T, et al. Serum SCUBE-1 levels in patients with diabetic retinopathy. Int Ophthalmol. 2019;[Epub ahead of print]. doi: 10.1007/s10792-019-01249-8.
25. Chiarelli F, Giannini C, Verrotti A, Mezzetti A, Mohn A. Increased concentrations of soluble CD40 ligand may help to identify type 1 diabetic adolescents and young adults at risk for developing persistent microalbuminuria. Diabetes Metab Res Rev. 2008;24(7):570-6.
26. Varo N, Vicent D, Libby P, Nuzzo R, Calle-Pascual AL, Bernal MR, et al. Elevated plasma levels of the atherogenic mediator soluble CD40 ligand in diabetic patients: a novel target of thiazolidinediones. Circulation. 2003;107(21):2664-9.
27. Lajer M, Tarnow I, Michelson AD, Jorsal A, Frelinger AL, Parving HH, et al. Soluble CD40 ligand is elevated in type 1 diabetic nephropathy but not predictive of mortality, cardiovascular events or kidney function. Platelets. 2010;21(7):525-32.
28. Ninomiya T, Perkovic V, de Galan BE, Zoungas S, Pillai A, Jardine M, et al. Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. J Am Soc Nephrol. 2009;20(8):1813-21.
29. Barrios C, Pascual J, Otero S, Soler MJ, Rodríguez E, Collado S, et al. Diabetic nephropathy is an independent factor associated to severe subclinical atheromatous disease. Atherosclerosis. 2015;242(1):37-44.
30. Momeni A, Dyani MA, Sedehi M, Ebrahimi E. Association between common carotid artery intima-media thickness and proteinuria in type 2 diabetic patients. Iran J Kidney Dis. 2015;9(4):311-5.
31. Lordkipanidzé M. Platelet turnover in atherothrombotic disease. Curr Pharm Des. 2012;18(33):5328-43.
32. Tarnow I, Michelson AD, Barnard MR, Frelinger AL 3rd, Aasted B, Jensen BR, et al. Nephropathy in type 1 diabetes is associated with increased circulating activated platelets and platelet hyperreactivity. Platelets. 2009;20(7):513-9.
33. Pamukcu B, Lip GY, Snezhitskiy V, Shantsila E. The CD40-CD40L system in cardiovascular disease. Ann Med. 2011;43(5):331-40.