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Plasma activity of the antioxidant enzymes in predicting diabetic nephropathy progression

  • Nephrology - Original Paper
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Abstract

Introduction

The aim of the study was to examine whether biomarkers of oxidative stress are predictors of diabetic nephropathy (DN) progression.

Methods

The study involved 45 patients with type 2 diabetes and DN and 15 healthy controls. Patients were followed for 3 years and the annual percentage change in eGFR was used to estimate the progression of DN. Patients with an annual percentage change in eGFR above the cutoff value of − 5.48%/year were classified in group 1, those with an annual percentage change in eGFR ≤ − 5.48%/year in group 2.

Results

The 28 patients in group 1 had the annual percentage change in eGFR of − 4.78 and 39.12%/year, and for the 17 patients in group 2 it ranged from − 24.86 to − 6.18%/year. At the onset of the study no significant differences were found between the groups in demographic, clinical or laboratory parameters. Plasma activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were significantly lower in patients than in the controls. During 3-year study kidney function and size changed insignificantly in group 1, while eGFR and kidney size decreased and proteinuria increased significantly in group 2. Multivariate linear regression analysis selected male gender, duration of diabetes, systolic blood pressure, fasting serum glucose, urine protein/creatinine ratio as factors associated with DN progression. Plasma activity of GPX and SOD were selected as positive predictors of annual percentage change in eGFR.

Conclusion

Besides already known factors, plasma activity of GPX and SOD were found to be significant independent predictors of DN progression.

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References

  1. Looker HC, Colombo M, Hess S, Brosnan MJ, Farran B, Dalton RN, SUMMIT Investigators et al (2015) Biomarkers of rapid chronic kidney disease progression in type 2 diabetes. Kidney Int 88:888–896. https://doi.org/10.1038/ki.2015.199

    Article  CAS  PubMed  Google Scholar 

  2. Agarwal R, Duffin KL, Laska DA, Voelker JR, Breyer MD, Mitchell PG (2014) A prospective study of multiple protein biomarkers to predict progression in diabetic chronic kidney disease. Nephrol Dial Transpl 29:2293–2302. https://doi.org/10.1093/ndt/gfu255

    Article  CAS  Google Scholar 

  3. Viazzi F, Russo GT, Ceriello A, Fioretto P, Giorda C, De Cosmo S, Pontremoli R (2019) Natural history and risk factors for diabetic kidney disease in patients with T2D: lessons from the AMD-annals. J Nephrol 32:517–525. https://doi.org/10.1007/s40620-018-00561-3

    Article  CAS  PubMed  Google Scholar 

  4. MacIsaac RJ, Ekinci EI, Jerums G (2014) Markers of and risk factors for the development and progression of diabetic kidney disease. Am J Kidney Dis 63(2 Suppl 2):S39-62. https://doi.org/10.1053/j.ajkd.2013.10.048

    Article  PubMed  Google Scholar 

  5. Sagoo MK, Gnudi L (2018) Diabetic nephropathy: is there a role for oxidative stress?. Free Radical Biol Med 116:50–63. https://doi.org/10.1016/j.freeradbiomed.2017.12.040

    Article  CAS  Google Scholar 

  6. Earle KA, Zitouni K, Pepe J, Karaflou M, Godbold J Jr (2016) Modulation of endogenous antioxidant defense and the progression of kidney disease in multi-heritage groups of patients with type 2 diabetes: Prospective Evaluation of Early Nephropathy and its Treatment (PREVENT). J Transl Med 14:234. https://doi.org/10.1186/s12967-016-0975-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Jha JC, Banal C, Chow BSM, Cooper ME, Jandeleit-Dahm K (2016) Diabetes and kidney disease: role of oxidative stress. Antioxid Redox Signal 25:657–684. https://doi.org/10.1089/ars.2016.6664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Mališ S, Savić Radojević A, Kovačević A, Čančar O, Pavlović D, Djukanović L (2018) Oxidative stress and other risk factors associated with diabetic nephropathy in type 2 diabetes mellitus. Biomedicinska Istraživanja 9:27–36. https://doi.org/10.7251/BII1801027M

    Article  Google Scholar 

  9. Fujita H, Fujishima H, Chida S, Takahashi K, Qi Z, Kanetsuna Y et al (2009) Reduction of renal superoxide dismutase in progressive diabetic nephropathy. J Am Soc Nephrol 20(6):1303–1313. https://doi.org/10.1681/ASN.2008080844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lewis P, Stefanovic N, Pete J, Calkin AC, Giunti S, Thallas-Bonke V et al (2007) Lack of the antioxidant enzyme glutathione peroxidase accelerates atherosclerosis in diabetic apolipoprotein E-deficient mice. Circulation 115(16):2178–2187. https://doi.org/10.1161/CIRCULATIONAHA.106.664250

    Article  CAS  PubMed  Google Scholar 

  11. Ayala A, Muñoz MF, Argüelles S (2014) Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev. https://doi.org/10.1155/2014/360438

    Article  PubMed  PubMed Central  Google Scholar 

  12. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130:461–470. https://doi.org/10.7326/0003-4819-130-6-199903160-00002

    Article  CAS  PubMed  Google Scholar 

  13. Misra HP, Fridovich I (1972) The role of superoxide anion in the autooxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247:3170–3175

    Article  CAS  Google Scholar 

  14. Gunzler WA, Kremers H, Flohe L (1974) An improved coupled test procedure for glutathione peroxidase in blood. Z Klin Chem Klin Biochem 12:444–448. https://doi.org/10.1515/cclm.1974.12.10.444

    Article  CAS  PubMed  Google Scholar 

  15. Jocelyn PC (1987) Spectrophotometric assay of thiols. Methods Enzymol 143:44–61. https://doi.org/10.1016/0076-6879(87)43013-9

    Article  CAS  PubMed  Google Scholar 

  16. Djukanović L, Lezaić VN, Dimković N, PeruničićPeković G, Bukvić D, Bajčetić S, Pavlović J, Bontić A, Zec ND, Momčilović D, Stojanović M (2012) Early detection of chronic kidney disease: collaboration of Belgrade nephrologists and primary care physicians. Nefrologia 32(1):59–66. https://doi.org/10.3265/Nefrologia.pre2011.Oct.11031

    Article  PubMed  Google Scholar 

  17. Rosner B (2015) Fundamentals of biostatistics, 8th edn. Brooks/Cole Cengage Learning, Boston

    Google Scholar 

  18. Misra PS, Szeto SG, Krizova A, Gilbert RE, Yuen DA (2020) Renal histology in diabetic nephropathy predicts progression to end-stage kidney disease but not the rate renal function decline. BMC Nephrol 21:285. https://doi.org/10.1186/s12882-020-01943-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Heerspink HJ, Desai M, Jardine M, Balis D, Meininger G, Perkovic V (2017) Canagliflozin slows progression of renal function decline independently of glycemic effects. J Am Soc Nephrol 28:368–375. https://doi.org/10.1681/ASN.2016030278

    Article  CAS  PubMed  Google Scholar 

  20. Ino J, Kasama E, Kodama M, Sato K, Eizumi H, Kawashima Y et al (2021) Multidisciplinary team care delays the initiation of renal replacement therapy in diabetes: a five-year prospective, single-center study. Intern Med Adv Publ. https://doi.org/10.2169/internalmedicine.4927-20

    Article  Google Scholar 

  21. Guo Y, Cui L, Ye P, Li J, Wu S, Luo Y (2018) Change of kidney function is associated with all-cause mortality and cardiovascular diseases: results from the Kailuan study. J Am Heart Assoc 7(21):1596. https://doi.org/10.1161/JAHA.118.010596

    Article  Google Scholar 

  22. Nojima J, Meguro S, Ohkawa N, Furukoshi M, Kawai T, Itoh H (2017) One-year eGFR decline rate is a good predictor of prognosis of renal failure in patients with type 2 diabetes. Proc Jpn Acad Ser B Phys Biol Sci 93(9):746–754. https://doi.org/10.2183/pjab.93.046

    Article  PubMed  PubMed Central  Google Scholar 

  23. Shimizu M, Furuichi K, Toyama T, Funamoto T, Kitajima S, Hara A, Research Group of Diabetic Nephropathy, the Ministry of Health, Labour, and Welfare of Japan and Japan Agency for Medical Research and Development et al (2018) Decline in estimated glomerular filtration rate is associated with risk of end-stage renal disease in type 2 diabetes with macroalbuminuria: an observational study from JDNCS. Clin Exp Nephrol 22(2):377–387. https://doi.org/10.1007/s10157-017-1467-9

    Article  PubMed  Google Scholar 

  24. National Kidney Foundation (2002) K/DOQI clinical practice guidelines for chronic ekidney disease: evaluation, classification and stratification (2002). Am J Kidney Dis 39(suppl 1):S1–S266. https://doi.org/10.1053/j.ajkd.2007.11.016

    Article  Google Scholar 

  25. Kaneto H, Katakami N, Kawamori D, Miyatsuka T, Sakamoto K, Matsuoka TA, Matsuhisa M, Yamasaki Y (2007) Involvement of oxidative stress in the pathogenesis of diabetes. Antioxid Redox Signal 9:355–366. https://doi.org/10.1089/ars.2006.1465

    Article  CAS  PubMed  Google Scholar 

  26. Bondeva T, Wolf G (2014) Reactive oxygen species in diabetic nephropathy: friend or foe? Nephrol Dial Transpl 29:1998–2003. https://doi.org/10.1093/ndt/gfu037

    Article  CAS  Google Scholar 

  27. Sedighi O, Makhlough A, Shokrzadeh M, Hoorshad S (2014) Association between plasma selenium and glutathione peroxidase levels and severity of diabetic nephropathy in patients with type two diabetes mellitus. Nephrourol Mon 6(5):e21355. https://doi.org/10.5812/numonthly.21355

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kumawat M, Sharma TK, Singh I, Singh N, Ghalaut VS, Vardey SK, Shankar V (2013) Antioxidant enzymes and lipid peroxidation in type 2 diabetes mellitus patients with and without nephropathy. N Am J Med Sci 5(3):213–219. https://doi.org/10.4103/1947-2714.109193

    Article  PubMed  PubMed Central  Google Scholar 

  29. Mimić-Oka J, Simić T, Djukanović L, Reljić Z, Davicević Z (1999) Alteration in plasma antioxidant capacity in various degrees of chronic renal failure. Clin Nephrol 51(4):233–241

    PubMed  Google Scholar 

  30. Chang JM, Kuo MC, Kuo HT, Chiu YW, Chen HC (2005) Increased glomerular and extracellular malondialdehyde levels in patients and rats with diabetic nephropathy. J Lab Clin Med 146(4):210–215. https://doi.org/10.1016/j.lab.2005.05.007

    Article  CAS  PubMed  Google Scholar 

  31. Sayed AA (2012) Ferulsinaic acid modulates SOD, GSH, and antioxidant enzymes in diabetic kidney. Evid Based Complement Altern Med. https://doi.org/10.1155/2012/580104

    Article  Google Scholar 

  32. Zoppini G, Targher G, Chonchol M, Ortalda V, Negri C, Stoico V, Bonora E (2012) Predictors of estimated GFR decline in patients with type 2 diabetes and preserved kidney function. Clin J Am Soc Nephrol 7:401–408. https://doi.org/10.2215/CJN.07650711

    Article  CAS  PubMed  Google Scholar 

  33. Hobeika L, Hunt KJ, Neely BA, Arthur JM (2015) Comparison of the rate of renal function decline in non-proteinuric patients with and without diabetes. Am J Med Sci 350:447–452. https://doi.org/10.1097/MAJ.0000000000000583

    Article  PubMed  PubMed Central  Google Scholar 

  34. Derubertis FR, Craven PA, Melhem MF (2007) Acceleration of diabetic renal injury in the superoxide dismutase knockout mouse: effects of tempol. Metabolism 56:1256–1264. https://doi.org/10.1016/j.metabol.2007.04.024

    Article  CAS  PubMed  Google Scholar 

  35. Al-Kateb H, Boright AP, Mirea L, Xie X, Sutradhar R, Mowjoodi A, Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group et al (2008) Multiple superoxide dismutase 1/splicing factor serine alanine15 variants are associated with the development and progression of diabetic nephropathy the diabetes control and complications trial/epidemiology of diabetes interventions and complications genetics study. Diabetes 57(1):218–228. https://doi.org/10.2337/db07-1059

    Article  CAS  PubMed  Google Scholar 

  36. Hamanishi T, Furuta H, Kato H, Doi A, Tamai M, Shimomura H et al (2004) Functional variants in the glutathione peroxidase-1(GPx-1) gene are associated with increased intima-media thickness of carotid arteries and risk of macrovascular diseases in Japanese Type 2 diabetic patients. Diabetes 53(9):2455–2460. https://doi.org/10.2337/diabetes.53.9.2455

    Article  CAS  PubMed  Google Scholar 

  37. Farid N, Inbal D, Nakhoul N, Evgeny F, Miller-Lotan R, Levy AP et al (2013) Vitamin E and diabetic nephropathy in mice model and humans. World J Nephrol 2(4):111–124. https://doi.org/10.5527/wjn.v2.i4.111

    Article  PubMed  PubMed Central  Google Scholar 

  38. Bolignano D, Cernaro V, Gembillo G, Baggetta R, Buemi M, D’Arrigo G (2017) Antioxidant agents for delaying diabetic kidney disease progression: a systematic review and meta-analysis. PLoS ONE. https://doi.org/10.1371/journal.pone.0178699

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported by Grant 175052 from the Serbian Ministry of Education, Science and Technological Development.

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Authors and Affiliations

  1. University of East Sarajevo, Faculty of Medicine, Foča, Bosnia and Herzegovina

    Marijana Kovačević, Snežana Mališ, Dragana Pavlović & Maksim Kovačević

  2. Department for Internal Medicine, University Hospital, Foča, Bosnia and Herzegovina

    Marijana Kovačević, Snežana Mališ, Dragana Pavlović & Maksim Kovačević

  3. University of Belgrade, School of Medicine, Dr Subotića starijeg 8, 11 000, Belgrade, Serbia

    Ana Savić Radojević & Ljubica Djukanović

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  1. Marijana Kovačević
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  2. Snežana Mališ
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  4. Maksim Kovačević
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  5. Ana Savić Radojević
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Correspondence to Ljubica Djukanović.

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Author Marijana Kovačević declares that she has no conflict of interest. Author Snežana Mališ declares that she has no conflict of interest. Author Dragana Pavlović declares that she has no conflict of interest. Author Maksim Kovačević declares that he has no conflict of interest. Author Ana Savić Radojević declares that she has no conflict of interest. Author Ljubica Djukanović declares that she has no conflict of interest.

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Kovačević, M., Mališ, S., Pavlović, D. et al. Plasma activity of the antioxidant enzymes in predicting diabetic nephropathy progression. Int Urol Nephrol 54, 1365–1372 (2022). https://doi.org/10.1007/s11255-021-03031-1

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