Document Type : Original Article
Authors
- Farzaneh Najafi 1
- Nasim Namiranian 2
- Delaram Razavi 3
- Javad Mohiti-Ardakani 4
- Masoud Rahmanian 5
- Roghaye Razavi 6
- Somayeh Gholami 7
1 Nephrology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2 Community & Preventive Medicine, Yazd Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
3 Biotechnology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
4 Department of Biochemistry and Molecular Biology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
5 Endocrinology, Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
6 Yazd Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
7 Epidemiology, Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Abstract
Background: Elevated serum levels of osteopontin (OPN) have been associated with cardiovascular disease, diabetic nephropathy, and autoimmune disease activity. The aim of this study was to investigate the relationship between OPN serum levels and renal damage in type 2 diabetes patients.
Methods: This analytical cross-sectional study was carried out in Yazd, Iran from April to September 2017. Micro-albuminuria and creatinine (Cr) in 750 patients were measured and 180 included patients were divided into the three groups of 60 subjects based on the level of micro-albuminuria; normal (group A), micro proteinuria (group B) and macro proteinuria (group C). Body weight, height, blood pressure, body mass index (BMI), HbA1c and OPN were assessed.
Results: Among 179 patients, 60 of them were normal for proteinuria, 59 patients had micro-proteinuria and 60 ones had macro- proteinuria. The mean age of participants was 58.96 ( ± 11.10) years (range 26-80 years), 90 patients (50.8%) were males and 88 ones (49.2%) were females. The mean OPN levels were significantly higher in group C compared to group B, and in group B compared to group A (P = 0.0001). Serum OPN was correlated positively with HbA1c (P: 0.012), Cr (P = 0.010) and glomerular filtration rate (GFR) (P = 0.002). There was a significant difference in the mean of OPN level among the subgroups with the history of ischemic heart disease (IHD) and HbA1C (P=0.035, and 0.047 respectively).
Conclusion: These findings suggest that OPN is involved in chronic disease activity, and there is an independent association between plasma levels of OPN, and nephropathy in diabetic patients.
Highlights
Farzaneh Najafi(Google scholar)(Pubmed)
Nasim Namiranian(Google scholar)(Pubmed)
Javad Mohiti-Ardakani(Google scholar)(Pubmed)
Masoud Rahmanian(Google scholar)(Pubmed)
RoghayeRazav(Google scholar)(Pubmed)
Somayeh Gholami(Google scholar))(Pubmed)
Keywords
1. Hellemons ME, Kerschbaum J, Bakker SJ, Neuwirt H, Mayer
B, Mayer G, et al. Validity of biomarkers predicting onset or progression of nephropathy in patients with Type 2 diabetes: a systematic review. Diabet Med. 2012;29(5):567-77. doi: 10.1111/j.1464-5491.2011.03437.x.
2. Orasanu G, Plutzky J. The pathologic continuum of diabetic vascular disease. J Am Coll Cardiol. 2009;53(5 Suppl):S35-42. doi: 10.1016/j.jacc.2008.09.055.
3. Al-Maskari F, El-Sadig M, Norman JN. The prevalence of macrovascular complications among diabetic patients in the United Arab Emirates. Cardiovasc Diabetol. 2007;6:24. doi: 10.1186/1475-2840-6-24.
4. Mackinnon B, Shakerdi L, Deighan CJ, Fox JG, O’Reilly DS, Boulton-Jones M. Urinary transferrin, high molecular weight proteinuria and the progression of renal disease. Clin Nephrol. 2003;59(4):252-8. doi: 10.5414/cnp59252.
5. 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;29(1):142- 4. doi: 10.2337/diacare.29.1.142.
6. Yamaguchi H, Igarashi M, Hirata A, Tsuchiya H, Sugiyama K, Morita Y, et al. Progression of diabetic nephropathy enhances the plasma osteopontin level in type 2 diabetic patients. Endocr J. 2004;51(5):499-504. doi: 10.1507/endocrj.51.499.
7. Zhou C, Wu J, Torres L, Hicks JM, Bartkowiak T, Parker K, et al. Blockade of osteopontin inhibits glomerular fibrosis in a model of anti-glomerular basement membrane glomerulonephritis. Am J Nephrol. 2010;32(4):324-31. doi: 10.1159/000319490.
8. Kelly DJ, Wilkinson-Berka JL, Ricardo SD, Cox AJ, Gilbert RE. Progression of tubulointerstitial injury by osteopontin-induced macrophage recruitment in advanced diabetic nephropathy of transgenic (mRen-2)27 rats. Nephrol Dial Transplant. 2002;17(6):985-91. doi: 10.1093/ndt/17.6.985.
9. Li C, Yang CW, Park CW, Ahn HJ, Kim WY, Yoon KH, et al. Long-term treatment with ramipril attenuates renal osteopontin expression in diabetic rats. Kidney Int. 2003;63(2):454-63. doi: 10.1046/j.1523-1755.2003.00751.x.
10. Usui HK, Shikata K, Sasaki M, Okada S, Matsuda M, Shikata Y, et al. Macrophage scavenger receptor-a-deficient mice are resistant against diabetic nephropathy through amelioration of microinflammation. Diabetes. 2007;56(2):363-72. doi: 10.2337/db06-0359.
11. Nicholas SB, Liu J, Kim J, Ren Y, Collins AR, Nguyen L, et al. Critical role for osteopontin in diabetic nephropathy. Kidney Int. 2010;77(7):588-600. doi: 10.1038/ki.2009.518.
12. Summary of revisions to the 2014 Clinical Practice Recommendations. Diabetes Care. 2014;37 Suppl 1:S4. doi: 10.2337/dc14-S004.
13. Al-Malki AL. Assessment of urinary osteopontin in association with podocyte for early predication of nephropathy in diabetic patients. Dis Markers. 2014;2014:493736. doi: 10.1155/2014/493736.
14. Comabella M, Pericot I, Goertsches R, Nos C, Castillo M, Blas Navarro J, et al. Plasma osteopontin levels in multiple sclerosis. J Neuroimmunol. 2005;158(1-2):231-9. doi: 10.1016/j.jneuroim.2004.09.004.
15. Gordin D, Forsblom C, Panduru NM, Thomas MC, Bjerre M,
Soro-Paavonen A, et al. Osteopontin is a strong predictor of incipient diabetic nephropathy, cardiovascular disease, and all-cause mortality in patients with type 1 diabetes. Diabetes Care. 2014;37(9):2593-600. doi: 10.2337/dc14-0065 .
16. Steinbrenner I, Cheng Y, Nadal J, Schmid M, Kotsis FK, Meiselbach H, et al. Osteopontin and its association with adverse events in the German Chronic Kidney Disease Study. Nephrol Dial Transplant. 2021;36(Suppl 1):gfab144-004. doi:
10.1093/ndt/gfab144.004.
-
Nawaz SS, Siddiqui K, Mujammami M, Alotaibi O, Alanazi
SS, Rafiullah M. Determinant of osteopontin levels in microvascular complications in patients with diabetes. Int J Gen Med. 2022;15:4433-40. doi: 10.2147/ijgm.s354220.
-
Kramer AB, Ricardo SD, Kelly DJ, Waanders F, van Goor H, Navis G. Modulation of osteopontin in proteinuria-induced renal interstitial fibrosis. J Pathol. 2005;207(4):483-92. doi: 10.1002/path.1856.
-
Lorenzen J, Krämer R, Kliem V, Bode-Boeger SM, Veldink H, Haller H, et al. Circulating levels of osteopontin are closely related to glomerular filtration rate and cardiovascular risk markers in patients with chronic kidney disease. Eur J Clin Invest. 2010;40(4):294-300. doi: 10.1111/j.1365- 2362.2010.02271.x.
-
Yan X, Sano M, Lu L, Wang W, Zhang Q, Zhang R, et al. Plasma concentrations of osteopontin, but not thrombin- cleaved osteopontin, are associated with the presence and severity of nephropathy and coronary artery disease in patients with type 2 diabetes mellitus. Cardiovasc Diabetol. 2010;9:70. doi: 10.1186/1475-2840-9-70.
-
Lorenzen J, Lovric S, Krämer R, Haller H, Haubitz M.
Osteopontin in antineutrophil cytoplasmic autoantibody- associated vasculitis: relation to disease activity, organ manifestation and immunosuppressive therapy. Ann Rheum Dis. 2010;69(6):1169-71. doi: 10.1136/ard.2009.113621.
22. Takemoto M, Yokote K, Nishimura M, Shigematsu T, Hasegawa T, Kon S, et al. Enhanced expression of osteopontin in human diabetic artery and analysis of its functional role in accelerated atherogenesis. Arterioscler Thromb Vasc Biol. 2000;20(3):624-8. doi: 10.1161/01.atv.20.3.624.
23. Mohamadpour AH, Abdolrahmani L, Mirzaei H, Sahebkar A, Moohebati M, Ghorbani M, et al. Serum osteopontin concentrations in relation to coronary artery disease. Arch Med Res. 2015;46(2):112-7. doi: 10.1016/j.arcmed.2015.02.005.
24. Ohmori R, Momiyama Y, Taniguchi H, Takahashi R, Kusuhara M, Nakamura H, et al. Plasma osteopontin levels are associated with the presence and extent of coronary artery disease. Atherosclerosis. 2003;170(2):333-7. doi: 10.1016/ s0021-9150(03)00298-3.
25. Kase S, Yokoi M, Saito W, Furudate N, Ohgami K, Kitamura M, et al. Increased osteopontin levels in the vitreous of patients with diabetic retinopathy. Ophthalmic Res. 2007;39(3):143- 7. doi: 10.1159/000102936.
-
)