درمان گلومرولواسکلروز فوکال و سگمنتال اولیه

نوع مقاله: مقاله پژوهشی

نویسندگان

1 مرکز تحقیقات نارسایی مزمن کلیه، گروه نفرولوژی کودکان، دانشکدة پزشکی، دانشگاه علوم پزشکی جندی-شاپور اهواز، ایران.

2 مرکز تحقیقات نارسایی مزمن کلیه، گروه نفرولوژی، دانشگاه علوم پزشکی جندی-شاپور اهواز، ایران.

چکیده

گلومرولواسکلروز فوکال و سگمنتال  (FSGS)یکی از علل شایع سندرم نفروتیک در افراد بالغ و اطفال می­باشد. این بیماری ممکن است بدون علت مشخص (اولیه یا ایدیوپاتیک) و یا ثانویه به آسیب قبلی گلومرولی (ثانویه) ایجاد گردد. در درمان این بیماری افتراق نوع اولیه از نوع  ثانویه مهم است، چرا که درمان با تضعیف­کننده­های سیستم ایمنی در بیشتر بیماران با نوع اولیه و نه نوع ثانویه اندیکاسیون دارد. بیماران مبتلا به FSGS اولیه درمان نشده که با پروتئینوری در حد نفروتیک (بیش از 5/3 گرم در روز) و هیپوآلبومینمی مراجعه کرده­اند به طور تیپیک به سمت بیماری مرحلۀ پایانی کلیه پیشرفت می­نمایند. به نظر می­رسد که FSGS  اولیه در 80-40 درصد موارد به پردنیزولون با دوز 1mg/kg/day (حداکثر دوز 80-60 میلی­گرم در روز) پاسخ می­دهد. البته معمولاً برای ایجاد رمیسیون در این بیماران، دورۀ طولانی درمان با استروئید برای حداقل 16- 12 هفته لازم است. به طور شایع در بیماران عود کننده و یا مقاوم به استروئید، از سیکلوسپورین با دوز تقریبی 4mg/kg/day -2  که در دو دوز منقسم داده می­شود به همراه با دوز پایین پردنیزولون (حداکثر 15 میلی­گرم در روز) استفاده می­شود. به علاوه از سایر داروها مانند سیکلوفسفاماید و مایکوفنولیت مفتیل نیز در بیماران مقاوم به استروئید و یا عود کننده با درجات متفاوتی از پاسخ استفاده شده است.

کلیدواژه‌ها


1-Ritz E, Rychlik I, Locatelli F, Halimi S. End-stage renal failure in type 2 diabetes: A medical catastrophe of worldwide dimensions. Am J Kidney Dis1999;34(5):795–808.

2-Beladi Musavi SS,  Hayati F, Talebnejad M, Mousavi M. What is the difference between causes of ESRD in Iran and developing countries? Shiraz E-Med J [Serial Online] 2012;13(2). Available from: URL: http://semj.sums.ac.ir/vol13/apr2012/90016.htm. Accessed on month day, year.

3-Beladi Musavi SS,  Hayati F, Alemzadeh Ansari MJ, Valavi E, Cheraghian B, Shahbazian HA, et al. Survival at 1, 3, and 5 Years in Diabetic and Nondiabetic Hemodialysis Patients. Iran J Kidney Dis 2010;4(1):74-7.

4-Perneger TV, Brancati FL, Whelton PK, Klag MJ. End-stage renal disease attributable to diabetes mellitus. Ann Intern Med 1994;121(12):912-8.

6-Beladi Musavi SS,  Sametzadeh M, Hayati F, Fatemi SM. Evaluation of acquired cystic kidney disease in patients on hemodialysis with ultrasonography. Iran J Kidney Dis 2010;4(3):223-6.

7-Van Dijk PC, Jager KJ, Stengel B, Grönhagen-Riska C, Feest TG, Briggs JD. Renal replacement therapy for diabetic end-stage renal disease: data from 10 registries in Europe (1991-2000). Kidney Int 2005;67(4):1489-99.

8-Haghighi AN,  Broumand B,  D'Amico M, Locatelli F, Ritz E. The epidemiology of end-stage renal disease in Iran in an international perspective.  Nephrol Dial Transplant 2002;17(1):28-32.

9-Malekmakan L, Haghpanah S, Pakfetrat M, Malekmakan A, Khajehdehi P. Causes of chronic renal failure among Iranian hemodialysis patients.  Saudi J Kidney Dis Transpl 2009;20(3):501-4.

10-Aghighi M, Mahdavi-Mazdeh M, Zamyadi M, Heidary Rouchi AR,  Rajolani H, Nourozi S. Changing epidemiology of end-stage renal disease in last 10 years in Iran. Iran J Kidney Dis 2009;3(4):192-6.

12-Beladi Musavi SS. Cause of primary nephrotic syndrome in adult patients in Khuzestan province. Abstract book of the 12th International Congress of Nephrology, Dialysis and Transplantation, Iran J Kidney Dis 2009;3:75.

14-Beladi Musavi SS, Hayati F, Shahbazian H. [Is the prevalence of focal and segmental glomerulosclerosis increasing in the Province of Khuzestan?] Jundishapur Sci Med J 2012;11(2):157-62. [In Persian]

26-Cattran DC, Rao P. Long-term outcome in children and adults with classic focal segmental glomerulosclerosis. Am J Kidney Dis 1998;32(1):72-9.

27-Chitalia VC, Wells JE, Robson RA, Searle M, Lynn KL. Predicting renal survival in primary focal glomerulosclerosis from the time of presentation. Kidney Int 1999;56(6):2236-42.

28-Banfi G, Moriggi M, Sabadini E, Fellin G, D'Amico G, Ponticelli C. The impact of prolonged immunosuppression on the outcome of idiopathic focal-segmental glomerulosclerosis with nephrotic syndrome in adults. A collaborative retrospective study. Clin Nephrol 1991;36(2):53-9.

29-Chun MJ, Korbet SM, Schwartz MM, Lewis EJ. Focal segmental glomerulosclerosis in nephrotic adults: presentation, prognosis, and response to therapy of the histologic variants. J Am Soc Nephrol 2004;15(8):2169-77.

30-Nash MA, Greifer I, Olbing H, Bernstein J, Bennett B, Spitzer A. The significance of focal sclerotic lesions of glomeruli in children. J Pediatr 1976;88(5):806-13.

31-Ponticelli C, Villa M, Banfi G, Cesana B, Pozzi C, Pani A, et al. Can prolonged treatment improve the prognosis in adults with focal segmental glomerulosclerosis? Am J Kidney Dis 1999;34(4):618-25.

32-Troyanov S, Wall CA, Miller JA, Scholey JW, Cattran DC. Focal and segmental glomerulosclerosis: definition and relevance of a partial remission. J Am Soc Nephrol 2005;16(4):1061-8.

33-Thomas DB, Franceschini N, Hogan SL, Ten Holder S, Jennette CE, Falk RJ, et al. Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants. Kidney Int 2006;69(5):920-6.

34-Beaman M, Howie AJ, Hardwicke J, Michael J, Adu D. The glomerular tip lesion: a steroid responsive nephrotic syndrome. Clin Nephrol 1987;27(5):217-21.

35-Winn MP, Conlon PJ, Lynn KL, Howell DN, Slotterbeck BD, Smith AH, et al. Linkage of a gene causing familial focal segmental glomerulosclerosis to chromosome 11 and further evidence of genetic heterogeneity. Genomics 1999;58(2):113-20.

36-Pollak MR. The genetic basis of FSGS and steroid-resistant nephrosis. Semin Nephrol 2003;23(2):141-6.

37-Ruf RG, Lichtenberger A, Karle SM, Haas JP, Anacleto FE, Schultheiss M, et al. Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome. J Am Soc Nephrol 2004;15(3):722-32.

38-Heering P, Braun N, Müllejans R, Ivens K, Zäuner I, Fünfstück R, et al. Cyclosporine A and chlorambucil in the treatment of idiopathic focal segmental glomerulosclerosis. Am J Kidney Dis 2004;43(1):10-8.

39-Ponticelli C, Rizzoni G, Edefonti A, Altieri P, Rivolta E, Rinaldi S, et al. A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome. Kidney Int 1993;43(6):1377-84.

40-Niaudet P. Treatment of childhood steroid-resistant idiopathic nephrosis with a combination of cyclosporine and prednisone. French Society of Pediatric Nephrology. J Pediatr 1994;125(6 Pt1):981-6.

41-Lieberman KV, Tejani A. A randomized double-blind placebo-controlled trial of cyclosporine in steroid-resistant idiopathic focal segmental glomerulosclerosis in children. J Am Soc Nephrol 1996;7(1):56-63.

42-Duncan N, Dhaygude A, Owen J, Cairns TD, Griffith M, McLean AG, et al. Treatment of focal and segmental glomerulosclerosis in adults with tacrolimus monotherapy. Nephrol Dial Transplant 2004;19(12):3062-7.

43-Segarra A, Vila J, Pou L, Arbós A, Quiles T, Piera LL. Combined therapy of tacrolimus and corticosteroids in cyclosporin-resistant or -dependent idiopathic focal glomerulosclerosis: a preliminary uncontrolled study with prospective follow-up. Nephrol Dial Transplant 2002;17(4):655-62.

44-Loeffler K, Gowrishankar M, Yiu V. Tacrolimus therapy in pediatric patients with treatment-resistant nephrotic syndrome. Pediatr Nephrol 2004;19(3):281-7.

45-Li X, Li H, Ye H, Li Q, He X, Zhang X, et al. Tacrolimus therapy in adults with steroid- and cyclophosphamide-resistant nephrotic syndrome and normal or mildly reduced GFR. Am J Kidney Dis 2009;54(1):51-8.

46-Gipson DS, Trachtman H, Kaskel FJ, Greene TH, Radeva MK, Gassman JJ, et al. Clinical trial of focal segmental glomerulosclerosis in children and young adults. Kidney Int 2011;80(8):868-78.

47-Choi MJ, Eustace JA, Gimenez LF, Atta MG, Scheel PJ, Sothinathan R, et al. Mycophenolate mofetil treatment for primary glomerular diseases. Kidney Int 2002; 61(3):1098-114.

48-Day CJ, Cockwell P, Lipkin GW, Savage CO, Howie AJ, Adu D. Mycophenolatemofetil in the treatment of resistant idiopathic nephrotic syndrome. Nephrol Dial Transplant 2002;17(11):2011-3.

49-Montané B, Abitbol C, Chandar J, Strauss J, Zilleruelo G. Novel therapy of focal glomerulosclerosis with mycophenolate and angiotensin blockade. Pediatr Nephrol 2003;18(8):772-7.

50-Cattran DC, Wang MM, Appel G, Matalon A, Briggs W. Mycophenolate mofetil in the treatment of focal segmental glomerulosclerosis. Clin Nephrol 2004;62(6):405-11.

51-Deegens JK, Wetzels JF. Immunosuppressive treatment of focal segmental glomerulosclerosis: lessons from a randomized controlled trial. Kidney Int 2011;80(8):798-801.

52-Siegel NJ, Gaudio KM, Krassner LS, McDonald BM, Anderson FP, Kashgarian M. Steroid-dependent nephrotic syndrome in children: histopathology and relapses after cyclophosphamide treatment. Kidney Int 1981;19(3):454-9.

53-Schulman SL, Kaiser BA, Polinsky MS, Srinivasan R, Baluarte HJ. Predicting the response to cytotoxic therapy for childhood nephrotic syndrome: superiority of response to corticosteroid therapy over histopathologic patterns. J Pediatr 1988;113(6):996-1001.

54-Cyclophosphamide treatment of steroid dependent nephrotic syndrome: comparison of eight week with 12 week course. Report of Arbeitsgemeinschaft für Pädiatrische Nephrologie. Arch Dis Child 1987;62(11):1102-6.

55-Tumlin JA, Miller D, Near M, Selvaraj S, Hennigar R, Guasch A. A prospective, open-label trial of sirolimus in the treatment of focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 2006;1(1):109-16.

56-Cho M, Hurley JK, Kopp JB. Sirolimus for focal segmental glomerulosclerosis is associated with nephrotoxicity. Am J Kidney Dis. 2007;49(2):310-7

57-Cho ME, Hurley JK, Kopp JB. Sirolimus therapy of focal segmental glomerulosclerosis is associated with nephrotoxicity. Am J Kidney Dis 2007;49(2):310-7.

58-Fervenza FC, Fitzpatrick PM, Mertz J, Erickson SB, Liggett S, Popham S, et al. Acute rapamycin nephrotoxicity in native kidneys of patients with chronic glomerulopathies. Nephrol Dial Transplant 2004;19(5):1288-92.

59-Ginsburg DS, Dau P. Plasmapheresis in the treatment of steroid-resistant focal segmental glomerulosclerosis. Clin Nephrol 1997;48(5):282-7.

60-Mitwalli AH. Adding plasmapheresis to corticosteroids and alkylating agents: does it benefit patients with focal segmental glomerulosclerosis? Nephrol Dial Transplant 1998;13(6):1524-8.

61-Feld SM, Figueroa P, Savin V, Nast CC, Sharma R, Sharma M, et al. Plasmapheresis in the treatment of steroid-resistant focal segmental glomerulosclerosis in native kidneys. Am J Kidney Dis 1998;32(2):230-7.

62-Godfrin Y, Dantal J, Bouhours JF, Heslan JM, Soulillou JP. A new method of measuring albumin permeability in isolated glomeruli. Kidney Int 1996;50(4):1352-7.