Skip to main navigation menu Skip to main content Skip to site footer

Original article

Vol. 141 No. 4142 (2011)

Intensity of cytosol expression of 8-OHdG in normal renal tubules is associated with the severity of renal fibrosis

  • JP Tsai
  • JH Liou
  • KT Yeh
  • HC Tai
  • YW Cheng
  • HR Chang
DOI
https://doi.org/10.4414/smw.2011.13268
Cite this as:
Swiss Med Wkly. 2011;141:w13268
Published
10.10.2011

Summary

INTRODUCTION:It has been proposed thatreactive oxygen species play a role in renal fibrosis. 8-OHdG, a metabolite of oxidative damage to leukocyte DNA, has been identified as a marker of oxidative stress in patients with chronic renal failure.

MATERIALS AND METHODS:Seventy-four patients following nephrectomy were retrospectively enrolled. Immunohistochemical analysis of the renal expression of 8-OHdG in the nephrectomised kidneys was performed and associations between renal expression of 8-OHdG and renal fibrosis were evaluated.

RESULTS:Patients with higher interstitial fibrosis scores (IFS) and glomerular fibrosis scores (GFS) had significantly higher serum creatinine, lower estimated glomerular filtration rate (eGFR), increased percentage of chronic kidney disease (CKD) and urothelial cell carcinoma. The renal tissues with higher IFS had lower expressions of 8-OHdG in normal tubular cytoplasm (NTc) (35.7% vs. 64.3%, p = 0.011) and normal tubular nuclei (NTn) (28.6% vs. 71.4%, p = 0.023). Univariate analysis showed that IFS and GFS correlated with the NTc 8-OHdG expression and IFS negatively correlated with NTn 8-OHdG expression. Multivariate stepwise regression revealed that serum creatinine (r = 0.351 for IFS, p = 0.021; r = 0.563 for GFS, p <0.001) and intensity of 8-OHdG expression in NTc (r = 0.397 for IFS, p = 0.01; r = 0.278 for GFS, p = 0.043) were the independent factors predicting IFS or GFS.

CONCLUSION:This study demonstrated that the intensity of 8-OHdG expression in NTc was associated with the severity of renal fibrosis.

References

  1. Knight JA. Diseases related to oxygen-derived free radicals. Ann Clin Lab Sci. 1995;25(2):111–21.
  2. Ha H, Lee HB. Reactive oxygen species and matrix remodeling in diabetic kidney. J Am Soc Nephrol. 2003;14(8 Suppl 3):S246–249.
  3. Okamura DM, Himmelfarb J. Tipping the redox balance of oxidative stress in fibrogenic pathways in chronic kidney disease. Pediatr Nephrol. 2009;24(12):2309–19.
  4. Measurement of DNA oxidation in human cells by chromatographic and enzymic methods. Free Radic Biol Med. 2003;34(8):1089–99.
  5. Domenici FA, Vannucchi MT, Jordao AA, Jr., Meirelles MS, Vannucchi H. DNA oxidative damage in patients with dialysis treatment. Ren Fail. 2005;27(6):689–94.
  6. Dincer Y, Sekercioglu N, Pekpak M, Gunes KN, Akcay T. Assessment of DNA oxidation and antioxidant activity in hypertensive patients with chronic kidney disease. Ren Fail. 2008;30(10):1006–11.
  7. Remuzzi G, Bertani T. Pathophysiology of progressive nephropathies. N Engl J Med. 1998;339(20):1448–56.
  8. Yamagishi S, Inagaki Y, Okamoto T, Amano S, Koga K, Takeuchi M. Advanced glycation end products inhibit de novo protein synthesis and induce TGF-beta overexpression in proximal tubular cells. Kidney Int. 2003;63(2):464–73.
  9. Ha H, Lee HB. Reactive oxygen species as glucose signaling molecules in mesangial cells cultured under high glucose. Kidney Int Suppl. 2000;77:S19–25.
  10. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2 Suppl 1):S1–266.
  11. Solez K, Colvin RB, Racusen LC, Sis B, Halloran PF, Birk PE, et al. Banff '05 Meeting Report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy ('CAN'). Am J Transplant. 2007;7(3):518–26.
  12. Tsai YY, Cheng YW, Lee H, Tsai FJ, Tseng SH, Lin CL, et al. Oxidative DNA damage in pterygium. Mol Vis. 2005;11:71–5.
  13. Brenner BM. Remission of renal disease: recounting the challenge, acquiring the goal. J Clin Invest. 2002;110(12):1753–8.
  14. Liu Y. Renal fibrosis: new insights into the pathogenesis and therapeutics. Kidney Int. 2006;69(2):213–7.
  15. Eberhardt W, Pfeilschifter J. Nitric oxide and vascular remodeling: spotlight on the kidney. Kidney Int Suppl. 2007(106):S9–S16.
  16. Huang XB, Ito F, Nakazawa H, Toma H. Increased expression of 8-hydroxydeoxyguanosine in acquired cystic disease of the kidney. Nephron. 1999;81(4):458–9.
  17. Cochrane AL, Ricardo SD. Oxidant stress and regulation of chemokines in the development of renal interstitial fibrosis. Contrib Nephrol. 2003;139:102–19.
  18. Fujii H, Nishijima F, Goto S, Sugano M, Yamato H, Kitazawa R, et al. Oral charcoal adsorbent (AST-120) prevents progression of cardiac damage in chronic kidney disease through suppression of oxidative stress. Nephrol Dial Transplant. 2009;24(7):2089–95.
  19. Shah SV, Baliga R, Rajapurkar M, Fonseca VA. Oxidants in chronic kidney disease. J Am Soc Nephrol. 2007;18(1):16–28.
  20. Jeong KH, Lee TW, Ihm CG, Lee SH, Moon JY, Lim SJ. Effects of sildenafil on oxidative and inflammatory injuries of the kidney in streptozotocin-induced diabetic rats. Am J Nephrol. 2009;29(3):274–82.
  21. Nomoto K, Tsuneyama K, Takahashi H, Murai Y, Takano Y. Cytoplasmic fine granular expression of 8-hydroxydeoxyguanosine reflects early mitochondrial oxidative DNA damage in nonalcoholic fatty liver disease. Appl Immunohistochem Mol Morphol. 2008;16(1):71–5.
  22. Chuma M, Hige S, Nakanishi M, Ogawa K, Natsuizaka M, Yamamoto Y, et al. 8-Hydroxy-2'-deoxy-guanosine is a risk factor for development of hepatocellular carcinoma in patients with chronic hepatitis C virus infection. J Gastroenterol Hepatol. 2008;23(9):1431–6.
  23. Akcay T, Saygili, Angican G, Yalcin V. Increased formation of 8-hydroxy-2'-deoxyguanosinein peripheral blood leukocytes in bladder cancer. Urol Int. 2003;71(3):271–4.
  24. Miyake H, Hara I, Kamidono S, Eto H. Prognostic significance of oxidative and damage evaluated by 8-hydroxy-2'-deoxyguanosine in patients undergoing radical nephrectomy for renal cell carcinoma. Urology. 2004;64(5):1057–61.
  25. Chang CH, Yang CM, Yang AH. Renal diagnosis of chronic hemodialysis patients with urinary tract transitional cell carcinoma in Taiwan. Cancer. 2007;109(8):1487–92.