Опыт применения циклоспорина А в лечении идиопатического фокального сегментарного гломерулосклероза

Фокальный сегментарный гломерулосклероз (ФСГС) является одним из наиболее прогностически неблагоприятных вариантов хронического гломерулонефрита. В последние десятилетия широкое распространение в лечении НС при ФСГС получил Циклоспорин А (ЦсА). Внастоящее время считается, что эффективность ЦсА при ФСГС связана с ингибицией кальцинейрин-обусловленного дефосфорилирования и уменьшением распада белка синаптоподина, результатом чего является стабилизация подоцитарного актинового цитоскелета, повреждаемого, в частности, факторами проницаемости, особенно при наличии определенной генетической предрасположенности. Ретроспективно проанализированы материалы наблюдений 49 больных с ФСГС. ЦсА применяли в 40 случаях у 36 больных (ЦсА-группа), в 24 случаях в дебюте заболевания, и в 16 – при рецидиве (4 лечились как в дебюте, так и при рецидиве). К контрольной группе отнесено 18 больных, лечившихся преднизолоном (ПЗ) или комбинацией ПЗ и циклофосфамида (ЦФ) в дебюте заболевания, причем у 5 из них при рецидиве НС применена терапия ЦсА. Результаты терапии в двух группах оказались сопоставимыми. С учетом характерного для ФСГС рецидивирующего течения, требующего длительной терапии, и значительной опасности серьезных побочных эффектов традиционно применяемых для лечения этого заболевания кортикостероидов, относительно безопасное многомесячное применение ЦсА, обеспечивающее стабильно безрецидивное течение заболевания, является в настоящее время оптимальным подходом к его терапии.

фокально-сегментраный гломерулосклероз, нефротический синдром, циклоспорин А, подоцитопатия, синаптоподин, focal segmental glomerulosklerosis, nephrotic syndrome, cyclosporine A, podocitopathy, sinaptopodin

1. Appel G.B., Glassock R.J. Glomerular, vascular, and tubulointerstitial diseases // Nephrology Self-Assesment Programm. 2005. Vol. 4. P. 11–153.

2. Appel G.B., Pollak M.R., D’Agati V. Focal and Segmental Glomerulosclerosis: Genetic and Spontaneous Causes. Comprehensive Clinical Nephrology 3rd edition. Elsevier, 2007. P. 217–231.

3. Bahiense-Oliveira M., Saldanha L.B., Andrade Mota E.L. et al. Primary glomerular disease in Brazil: 1979–1999. Is the frequency of FSGS increasing? // Clin. Nephrol. 2004. Vol. 61. P. 90–97.

4. Banfi G., Moriggi M., Sabadini E. et al. The impact of prolonged immunosupression on the outcome of idiopathic focal-segmental glomerulosclerosis with nephritic syndrome in adults // Clin. Nephrol. 1991. Vol. 36 (2). P 53–59.

5. Beaufils H., Alphonse J.C., Guedon J. et al. Focal glomerulosclerosis: natural history and treatment. A report of 70 cases // Nephrol. 1978. Vol. 21 (2). P. 75–85.

6. Braden G.L., Mulhern J.G., O’Shea M.N. et al. Changing incidence of glomerular disease in adult // Am. J. Kidney Dis. 2000. Vol. 35. P. 878–883.

7. Braun N., Schmutzler F., Lange C. et al. Immunosupressive treatment for focal segmental glomerulosclerosis in adults (review) // Cochrane Database of systematic rewiews 2008, Issue 3. Art. No.: CD 003233. DOI:10.1002/14651858. CD003233.pub2.

8. Cameron J.S., Turner D.R, OggC.S. et al. The long term prognosis of patient with focal segmental glomerulosclerosis // Clin. Nehrol. 1978. Vol. 10 (6). P. 213–218.

9. Cattran D.C. Cyclosporin in idiopathic glomerular disease associated with the nephritic syndrome: Workshop recommendations // Kidney Int. 2007. Vol. 72. P. 1429–1447.

10. Cattran D.C., Rao P. Long-term outcome in children and adults with classic focal segmental glomerulosclerosis // Am. J. Kidney Dis. 1998. Vol. 32 (1). P. 72–79.

11. Cattran D.C., Appel G.B., Herbet L.A. et al. A randomized trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis. North America Nephrotic Syndrome study Group // Kidney Int. 1999. Vol. 56 (6). P. 2220–2226.

12. Chitalia V.C., Wells J.E., Robson R.A. et al. Predicting renal survival in primary focal glomerulosclerosis from the time of presentation // Kidney Int. 1999. Vol. 56 (6) P. 2236–2242.

13. Chun M.J., Korbet S.M., Schwartz M.M. et al. FSGS in nephrotic adults: Presentation, prognosis, and response to therapy of the histologic variants // J. Am. Soc. Nephrol. 2004. Vol. 15. P. 2169–2177.

14. Clement L.C., Avila-Casado C., Macé C. Podocyte-secreted angiopoietin-like-4 mediates proteinuria in glucocorticoid-sensitive nephrotic syndrome // Nat. Med. 2011. Vol. 17 (1) P. 117–122.

15. Crew R.J., Appel G.B. Focal Segmental glomerulosclerosis. The NKF Primer on Kidney Disease, 4th ed. Philadelphia. Elsevier, 2005. P. 178–182.

16. D’Agati V. Pathologic classification of focal segmental glomerulosclerosis // Semin. Nephrol. 2003. Vol. 23. P. 117–135.

17. DantalvJ., Bigot E., Bogers W. et al. Effect of plasma protein absorbtion on protein excretion in kidney-transplant recipients with recurrent nephritic syndrome // N. Engl. J. Med. 1994. Vol. 330. P. 7–11.

18. Deegens J.K., Steenbergen E.J., Wetzels J.F. Review on diagnosis and treatment of focal segmental glomerulosclerosis // Neth. J. Med. 2008. Vol. 66. P. 3–12.

19. Ehrich J.H., Pape L., Schiffer M. Corticosterod-resistant nephritic syndrome with focal and segmental glomerulosclerosis: an update of treatment options in children // Paediatr. Drugs. 2008. Vol. 10 (1). P. 9–22.

20. Faul C. The actin cytoskeleton of kidney podocytes is a direct target of the antiprotenuric effect of cyclosporine // A. Nat. Med. 2008. Vol. 14. P. 931–938.

21. Faurschou M. Malignancies in Wegener’s granulomatosis: incidence and relation to cyclophosphamide therapy in a cohort of 293 patients // J. Rheumatol. 2008. Vol. 35. P. 100–105.

22. Garin E.H., Mu W., Arthur J.M., etal. Urinary CD80 is elevated in minimal change disease but not in focal segmental glomerulosclerosis // Kidney Int. 2010. Vol. 78 (3). P. 296–302.

23. Genovese G, Friedman D.S., Ross M.D. et al. Assotiation of typanolytic ApoL 1 variants with kidney disease in African Americans // Science. 2010. Vol. 329. P. 841–845.

24. Goumenos D.S., Tsagalis G., El Nachas A.M. et al. Immunosupressive treatment of idiopathic focal segmental glomerulosklerosis: a five year follow-up study // Nephron. Clin. Pract. 2006. Vol. 104. P. 75–89.

25. Haas M., Meehan S., Karrison T.G. et al. Changing etiologies of unexplained adult nephrotic syndrome. A comparison of renal biopsy findings from 1976–1979 and 1995–1997 // Am. J. Kidney Dis. 1997. Vol. 30. P. 621–631.

26. Hara M., Yanagihar T., Kihara I. Urinary podocytes in primary focal segmental glomerulosclerosis // Nephron. 2001. Vol. 89. P. 342–347.

27. Ioannidis J.P. Predictors of sustained amenorrhea from pulsed intravenous cyclophosphamide in premenopausal women with systemic lupus erythematosus // J. Rheumatol. 2002. Vol. 29. P. 2129–2135.

28. Kitiyakara C., Eggers P., Kopp J.B. Twenty-one year rends in ESRD due to FSGS in the United States // Am. J. Kidney Dis. 2004. Vol. 44. P. 815–825.

29. Klein M., Radhakrishnan J., Appel G.B. Cyclosporin treatment of glomerular diseases // Annu. Rev. Med. 1999. Vol. 50. P. 1–15.

30. Kopp J.B., Nelson G.W., Sampath K. et al. APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy // J. Am. Soc. Nephrol. 2011. Vol. 22 (11). P. 2129–2137.

31. Korbet S.M., Schwartz M.M., Lewis E.J. Primary focal segmental glomerulosclerosis: clinical course and response to therapy // Am. J. Kidney Dis. 1994. Vol. 23 (6). P. 773–783.

32. Korbet S.M. Treatment of focal segmental glomerulosclerosis // Kidney Int. 2002. Vol. 62. P. 2301–2310.

33. Lagrue G., Laurent J., Belghiti D. et al. Cyclosporine and idiopathic nephrotic syndrome // Lancet. 1986. Vol. 2. P. 692–693.

34. Lieberman K.V., Tejani A. Pediatric Nephrology Study Group: A randomized double-blind trial of cyclosporine in steroid resistant FSGS in children // J. Am. Soc. Nephrol. 1996. Vol. 7. P. 56–63.

35. Maher E.R., Sweny P., Chappel M. et al. Cyclosporine in the treatment of steroid-responsive and steroid-resistant nephrotic syndrome in adults // Nephrol Dial Transplant. 1988. Vol. 3. P. 728–732.

36. Matalon A., Markowitz G.S., Joseph R.E. et al. Plasmapheresis treatment of recurrent FSGS in adult transplant recipients // Clinnephrol. 2001. Vol. 56. P. 271–278.

37. Matalon A., Valeri A., Appel G.B. Treatment of focal segmental glomerulosclerosis // Semin. Nephrol. 2000. Vol. 20. P. 309–317.

38. McCarthy E.T., Sharma M., Savin V.J. Circulating permeability factors in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis // Clin. J. Am. Soc. Nephrol. 2010. Vol. 5 (11). P. 2115–2121.

39. Melocoton T.L., Kamil E.S., Cohen A.H. Long-term cyclosporine A treatment in steroid-resistant and steroid-dependent nephrotic syndrome // Am. J. Kidney Dis. 1991. Vol. 18. P. 583–588.

40. Mendoza S.A., Reznik V.M., Griswold W.R. et al. Treatment of steroid resistant focal segmental glomerulosclerosis with pulse methyl-prednisolone and alkylating agents // Pediatr. Nephrol. 1990. Vol. 4. P. 303–307.

41. Meyrier A., Collaborativa Group of the Societ de Nephrologie. Cyclosporine in the treatment of nephrosis // Am. J. Nephrol. 1989. Vol. 9. P. S65–S71.

42. Meyrier A., Simon P., Perret G. et al. Remission of idiopathic nephrotic syndrome after treatment with cyclosporine // BMJ. 1986. Vol. 292. P. 789–792.

43. KDIGO: Clinical Practice Guideline for Glomerulonephritis, 2012.

44. Neuhaus T.J., Burger H.R., Klingler M. et al. Long-term low-dose cyclosporin A in steroid-dependent nephrotic syndrome of childhood // Eur. J. Pediatr. 1992. Vol. 51. P. 775–778.

45. Niaudet P., Broyer M., Habib R. Treatment of idiopathic nephrotic syndrome with cyclosporine A in children // Clinnephrol. 1991. Vol. 35. P.S31–S36.

46. Niaudet P. French Society of Pediatric Nephrolology: Treatment of childhood steroid-resistant idiopathic nephrosis with a combination of cyclosporine and prednisone // J. Pediatr. 1994. Vol. 125. P. 981–986.

47. Pei Y., Cattran D., Delmore T. et al. Evidence suggesting under-treatment of adults with idiopathic FSGS // Am. J. Med. 1987. Vol. 82. P. 938–944.

48. Ponticelli C., Glassock R.J. “Treatment of primary glomerulonephritis” Second edition. Oxford University Press,2009. P. 215–260.

49. Ponticelli C., Passerini P. Other immunosuppressive agents for FSGS // Semin. Nephrol. 2003. Vol. 23. P. 242–248.

50. Ponticelli C., Rizzoni G., Edefonti A. et al. A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome // Kidney Int. 1993. Vol. 43 (6). P. 1377–1384.

51. Reiser J. Induction of B7-1 inpodocytes is associated with nephrotic syndrome // J. Clin. Invest. 2004. Vol. 113 (10). P. 1390–1397.

52. Rydel J.J., Korbet S.M., Borok R.Z. et al. Focal segmental glomerular sclerosis in adults: presentation, course, and respons to treatment // Am. J. Kidney Dis. 1995. Vol. 25 (4). P. 534–542.

53. Shanklad S.J. The podocyte’s response to injury: role in proteinuria and glomerulosclerosis // Kidney International. 2006. Vol. 69. P. 2131–2147.

54. Tanaka R., Yoshikawa N., Kitano Y. et al. Long-term low-dose cyclosporin treatment in children with steroid-dependent nephrotic syndrome // Pediatr. Nephrol. 1993. Vol. 7. P. 249–252.

55. Tejani A., Suthanthiran M., Pomerantz A. A randomized controlled trial of low-dose prednisone and cyclosporine versus high-dose prednisolone in nephrotic syndrome of children // Nephron. 1991. Vol. 59. P. 96–99.

56. Troyanov S., Wall C.A., Miller J.A. et al. Toronto Glomerulonephritis Registry Group. Focal and segmental glomerulosclerosis: definition and prevalence of a partial remission // J. Am. Soc. Nephrol. 2005. Vol. 16 (4). P. 1061–1068.

57. Tune B.M., Kirpekor R., Sibley R. et al. IV methylprednisolone and oral alkylating agent therapy of prednisolone resistant pediatric FSGS: Long-term follw up // Clin. Neprol. 1995. Vol. 43. P. 83–88.

58. Velosa J.A., Donadio J.Jr., Holley K.E. Focal sclerosing glomerulopathy: a clinicopathologic study // Mayo Clin. Proc. 1975. Vol. 50 (3). P. 121–133.

59. Webb K.L, Saragent P., Burke J.R. Cyclosporin therapy in steroid-dependent nephritic syndrome // J. Paediatr. Health. 1993. Vol. 29. P. 188–191.

60. Wehrmann M., Bohle A., Held H. et al. Long-term prognosis of focal sclerosing glomerulonephritis An analysis of 250 cases with particular regard to tubulointerstitial changes // Clin. Nephrol. 1990. Vol. 33 (3). P. 115–122.

61. Wei C., El Hindi S., Li J., Fornoni A. et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis // Nat. Med. 2011. Vol. 17 (8). P. 952–960.

62. Wiggins R.C. The spectrum of podocytopathies: A unifying view of glomerular diseases // Kidney International. 2007. Vol. 71. P. 1205–1214.