Clinical implications of DNA-topoisomerases examination in renal biopsies from nephritis patients

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Aim. To study expression of topoisomerases (TI) I and Ha (DNA-bound enzymes involved in transcription
and replication) in renal tissue as markers of activity and prognosis of glomerulonephritis
(GN) decisive for choice of immunodepressive therapy.
Material and methods. TI expression was studied immunohistochemically in renal biopsies from 177
patients with different morphological variants of GN and in the samples of unaffected kidney tissue removed
in 12 patients for local tumors.
Results. There are definite differences between proliferative and поп-proliferative GN variants - elevation
of TI levels and monocytic infiltration in proliferative GN. Focal-segmental glomerulosclerosis
is characterized by a high TI Ila level in mesangial cells and monocytic infiltration of the glomeruli
which are typical for inflammation. A statistical relationship between TI levels in mesangial cells and
glomerular epithelium suggests a pathogenetic relation between these links of the pathological process.
Molecular markers of activation and proliferation of cells and direct inductors of the inflammatory
process (cells of monocytic infiltrate) closely correlated with the activity index - an integral indicator
of inflammatory activity, as well as with the integral indicator of sclerotic processes in renal tissuesclerosis index.
Monocytic infiltration in the interstitium correlated both with morphological manifestations
of activity, progression of nephritis and their clinical equivalents. In high TI expression GN resistance
to immunodepressive therapy rose. To overcome the resistance, immunodepressive therapy
must be more active - large doses and duration of treatment. In patients with lupus nephritis and merenal GN
prognosis was worse in the presence of high TI expression in mesangial cells
and epithelium of the renal canaliculi.
Conclusion. The authors are the first to demonstrate TI expression in renal tissue of GN patients, correlation
of its level with activity of renal process as well as its role in prediction of response to treatsangiocapillary
ment and the rate of renal failure progression. It is suggested that high TI expression entails a progressive
course of GN.


  1. Glicklich D.. Acharya A. Mycophenolate mofetil therapy for lupus nephritis refractory to intravenous cyclophosphamide. Am.J. Kidney Dis. 1998; 32 (2): 318-322.
  2. Ponticelli C., Finzi A. F., Ferraccioli G. Cyclosporine-induced nephrotoxicity in autoimmune diseases [letter]. Kidney Int. 1999; 55: 2075-2076.
  3. Мухин Н. А., Тареева И. Е., Краснова Т. Н. и др. Сандиммун (циклоспорин А) в лечении хронического гломерулонефрита. Клин, фармакол. и тер. 1995; 2: 38-39.
  4. Gel/en M. DNA topoisomerases. Annu. Rev. Biochem. 1981; 50: 879-910.
  5. Wang J. C. DNA topoisomerases. Ann. Rev. Biochem. 1985; 54: 665-697.
  6. D'Arpa P., Liu L. F. Cell cycle-specific and transcription-related phosphorylation of mammalian topoisomerase I. Exp. Cell Res. 1995; 217: 125-131.
  7. Baker S. D., Wadkins R. M., Stewart С F. et al. Cell cycle analysis of amount and distribution of nuclear DNA topoisomerase I as determined by fluorescence digital imaging microscopy. Cytometry 1995; 9: 134-145.
  8. Hwang J., Hwong C. L. Cellular regulation of mammalian DNA topoisomerases. Adv. Pharmacol. 1994; 29: 167-189.
  9. Nakopoulou L., Zervas A., Ch Lasaris A. et al. Predictive value of topoisomerase II alfa immunostaining in urothelial bladder carcinoma. J. Clin. Pathol. 2001; 54: 309-313.
  10. Rudolph P., Bonkhon F., Keltner E. et al. Prognostic relevance of Ki-67 and topoisomerase II alpha expression in soft tissue sarcoma. Pathol Res. Pract. 1997; 193: 334.
  11. Rudolph P., Macgrogan G., Bonichon F. et al. Prognostic significance of Ki-67 and topoisomerase II alpha expression in infiltrating ductal breast cancer. A multivariate analysis of 863 cases. Breast Cancer Res. Treat. 1999; 55: 61-71.
  12. Abigerges D., Armand J. P., Chabot G. G. et al. Phase I and pharmacology study of intoplicine (RP 60475, NSC 645008), novel topoisomerase 1 and II inhibitor, in cancer patients. Anticancer Drugs 1996; 7: 166-174.
  13. Kollmannsberger C., Mross K., Jakob A. et al. Topotecan - A novel topoisomerase I inhibitor: pharmacology and clinical experience. Oncology 1999; 56: 1 - 12.
  14. O'Reilly S., Rowinsky E. K., Slichenmyer W. et al. Phase I and pharmacology study of topotecan in patients with impaired rerial function. J. Clin. Oncol. 1996; 14: 3062-3073.
  15. Шилов Е. М., Краснова Т. Н., Иванов А. А. и др. Прогноз волчаночного нефрита при лечении сверхвысокими дозами циклофосфана. Тер. арх. 1992; 8: 63-68.
  16. Ivanovo L. V., Rudolph P., Kellner U. et al. Expression of DNA topoisomerases in chronic proliferative kidney disease. Kidney Int. 2000; 58 (4): 1603-1612.
  17. Ivanovo L. V., Rudolph P., Shilov Y. M. et al. Correlation between the expression of DNA topoisomerases I and Па and clinical parameters in kidney disease. Am. J. Kidney Dis. 2001; 38 (5): 1028-1037.

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