Research Article


DOI :10.5222/j.child.2017.077   IUP :10.5222/j.child.2017.077    Full Text (PDF)

Evaluation the Effectiveness of Intravenous Cyclophosphamide Treatment in Children with Lupus Nephritis

Işık Odaman AlSevinç EmreIlmay BilgeAlev YılmazBağdagül Yavaş Aksu

Objective: Renal involvement in systemic lupus erythematosus is an important cause of morbidity and mortality. Cyclophosphamide is widely used in the treatment of lupus nephritis. The aim of this study is to evaluate the effectiveness of intravenous cyclophosphamide treatment in children with lupus nephritis. Material and Method: In this study, 28 patients with lupus nephritis treated by intravenous pulse cyclophosphamide between the years 1999, and 2011 in Istanbul Faculty of Medicine, Department of Pediatric Nephrology were investigated retrospectively. Clinical history, presenting symptoms and findings, laboratory analysis, results of renal biopsy, treatment methods and prognosis were evaluated. Results: Proteinuria was determined in 27 (96.5%), macroscopic hematuria in 4 (14.3%), hypertension in 15 (53.5%), and renal failure in 11 patients (39.2%) as initial presentations. The most frequent extrarenal clinical findings were arthritis/arthralgia (67.9%), constitutional (64.3%) and skin findings (60.7%). The most frequent histopathological finding of lupus nephritis patients in our study group was Class 4 lupus nephritis (53.5%), followed by Class 2 (21,6%), Class 3 (10,7%) and Class 5 (3.5%) nephritis respectively. Renal remission was obtained in 21 (75%) patients throughout 62.7±49 (6-204) months of follow up period in study group. Nineteen patients (67.8%) were in remission in terms of both renal and extrarenal findings. Morbidity ratio (ESRF) was 14.2%, and mortality rate was 3.5% in our study group. ESRF and death in the study group were statistically related to increased serum creatinine levels during the initial presentation (p: 0.047). Side effects of intravenous cyclophosphamide were detected in 39.2% of the patients, while most frequent side effect was neutropenia (21.4%). Conclusion: In this study, intravenous cyclophosphamide treatment was determined as effective and reliable with minimum side effects in order to obtain renal and extrarenal remission in patients with pediatric lupus nephritis. The presence of high serum creatinine during the initial presentation was found as a poor prognostic factor. 

DOI :10.5222/j.child.2017.077   IUP :10.5222/j.child.2017.077    Full Text (PDF)

Lupus Nefritli Çocuklarda İntravenöz Siklofosfamid Tedavisinin Etkinliğinin Değerlendirilmesi

Işık Odaman AlSevinç EmreIlmay BilgeAlev YılmazBağdagül Yavaş Aksu

Amaç: Sistemik lupus eritematozus seyrinde renal tutulum önemli morbidite ve mortalite nedenidir. Lupus nefriti tedavisinde siklofosfamid yaygın olarak kullanılmaktadır. Bu çalışmadaki amacımız, çocuklardaki lupus nefritinde intravenöz siklofosfamid tedavisinin etkinliğini değerlendirmektir. Gereç ve Yöntem: İstanbul Tıp Fakültesi Çocuk Nefrolojisi Bilim Dalı tarafından 1991-2011 yılları arasında intravenöz siklofosfamid tedavisi alan 28 lupus nefritli hasta retrospektif olarak değerlendirildi. Tüm hastalarda öykü, başvuru sırasındaki bulgu ve belirtiler, laboratuvar tetkikleri, renal biyopsi sonuçları, tedavi ve prognoza ait veriler kaydedildi. Bulgular: Başvuru sırasında, 27 hastada (%96.5) proteinüri, 4 hastada (%14.3) makroskopik hematüri, 15 hastada (%53.5) hipertansiyon, 11 hastada (%39.2) ise böbrek yetersizliği saptandı. En sık saptanan ekstrarenal klinik bulgular artrit/artralji (%67.9), konstitüsyonel bulgular (%64.3) ve cilt bulguları (%60.7) idi. Hastalarımızda histopatolojik bulgu olarak en sık Class 4 (%53.5), daha sonra sırasıyla Class 2 (%21.6), Class 3 (%10.7) ve Class 5 (%3.5) lupus nefriti saptandı. Çalışma grubunda toplam 62.7±49 aylık (6-204 ay) izlem boyunca 21 hastada (%75) renal remisyon sağlandı. On dokuz hasta (%67.8) hem renal hem de ekstrarenal bulgular açısından remisyonda idi. Son dönem böbrek yetersizliği gelişme oranı %14.2 ve mortalite oranı %3.5 olarak belirlendi. Lupus nefriti vakalarında SDBY ve ölüm başlangıçtaki serum kreatinin yüksekliği ile istatistiksel olarak ilişkili bulundu (p: 0.047). Çalışma grubundaki hastaların %39.2’sinde intravenöz siklofosfamide bağlı yan etki görülürken, en sık görülen yan etki nötropeni (%21.4) idi. Sonuç: Bu çalışmamızda, pediyatrik lupus nefriti vakalarında intravenöz siklofosfamid tedavisinin minimal yan etki ile renal ve ekstrarenal remisyon sağlanmasında etkin ve güvenilir olduğu gösterilmiştir. Başlangıçtaki serum kreatinin yüksekliği kötü prognostik faktör olarak bulunmuştur


PDF View

References

  • 1. Bilge I. Sistemik lupus eritamatozus. In: Olcay Neyzi, Türkan Ertuğrul (eds): Pediatri. Nobel Tıp Kitabevleri, İstanbul. 2010:1257-61. google scholar
  • 2. Hochberg MC. Updating the American College of Rheumatology revised criteria for the sınıfification of systemic lupus erythematosus. Arthritis and Rheumatism 1997:40:1725. https://doi.org/10.1002/art.1780400928 google scholar
  • 3. The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr 1981;98(4):561-4. https://doi.org/10.1016/S0022-3476(81)80760-3 google scholar
  • 4. Niaudet P, Salomon R. Systemic lupus erythematosus. In: Avner ED, Harmon WE, Niaudet P (eds): Pediatric Nephrology, Springer 2009:1127-53. https://doi.org/10.1007/978-3-540-76341-3_47 google scholar
  • 5. Schwartz MM, Lan SP, Bernstein J, Hill GS, Holley K, Lewis EJ. Irreproducibility of the activity and chronicity indices limits their utility in the management of lupus nephritis. Lupus Nephritis Collaborative Study Group. Am J Kidney Dis 1993;21:374-7. https://doi.org/10.1016/S0272-6386(12)80263-0 6. Boumpas DT, Austin HA 3rd, Vaughn EM, Klippel JH, Steinberg AD, Yarboro CH, et al. Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet 1992;340:741-5. https://doi.org/10.1016/0140-6736(92)92292-N google scholar
  • 7. Şirin A, Emre S, Nayır A, Bilge I. Nefroloji. In: Devecioğlu Ö, Öneş Ü, Ünüvar E (eds): Pediatride Rutinler, İstanbul. 2005:485-545. google scholar
  • 8. Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976;58:259-63. google scholar
  • 9. Mok CC. Update on the therapies of severe lupus nephritis. Current Rheumatology Reviews 2006;2:186-90. https://doi.org/10.2174/157339706776876026 google scholar
  • 10. Baştuğ F, Poyrazoğlu H, Gündüz Z, Tülpar S, Düşünsel R. Juvenil lupus eritematozus: Fourteen years of experience. Turk J Rheumatol 2011;26(4):308- 15. https://doi.org/10.5606/tjr.2011.049 google scholar
  • 11. Caeiro F, Michielson FM, Bernstein R, Hughes GR, Ansell BM. Systemic lupus erythematosus in childhood. Ann Rheum Dis 1981;40:325-31. https://doi.org/10.1136/ard.40.4.325 google scholar
  • 12. Bakr A. Epidemiology treatment and outcome of childhood systemic lupus erythematosus in Egypt. Pediatr Nephrol 2005;20:1081-6. https://doi.org/10.1007/s00467-005-1900-2 google scholar
  • 13. Emre S, Bilge I, Sirin A, Kılıcaslan I, Nayır A, Oktem F, et al. Lupus nephritis in children: Prognostic significance of clinicopathological findings nephron. 2001;87:118-26. google scholar
  • 14. Gourley MF, Austin HA 3rd, Scott D, Yarboro CH, Vaughan EM, Muir J, et al. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med 1996;125(7):5495-57. https://doi.org/10.7326/0003-4819-125-7-199610010-00003 google scholar
  • 15. Ioannidis JP, Boki KA, Katsorida ME, Drosos AA, Skopouli FN, Boletis JN, et al. Remission, relapse, and re-remission of proliferative lupus nephritis treated with cyclophosphamide. Kidney International 2000;57: 258-64. https://doi.org/10.1046/j.1523-1755.2000.00832.x google scholar
  • 16. Liang TJ. Gastrointestinal vasculitis and pneumatosis intestinalis due to systemic lupus erythematosus: Successful treatment with pulse intravenous cyclophosphamide. Am J Med 1988;85:555-8. https://doi.org/10.1016/S0002-9343(88)80096-2 google scholar
  • 17. Rosenbaum JT, Simpson J, Neuwelt CM. Successful treatment of optic neuropathy in association with systemic lupus erythematosus using intravenous cyclophosphamide. Br J Ophthalmol 1997;81:130-2. https://doi.org/10.1136/bjo.81.2.130 google scholar
  • 18. Schnabel A, Reuter M, Gross WL. Intravenous pulse cyclophosphamide in the treatment of interstitial lung disease due to collagen vascular diseases. Arthritis Rheum 1998;41:1215-20. https://doi.org/10.1002/1529-0131(199807)41: 73.0.CO;2-Y google scholar
  • 19. Croca S, Rodrigues T, Isenberg DA. Assessment of a lupus nephritis cohort over a 30-year period. Rheumatology 2011;50:1424-30. https://doi.org/10.1093/rheumatology/ker101 google scholar
  • 20. Steinberg AD, Steinberg SC. Long-term preservation of renal functionin patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only. Arthritis Rheum 1991;34(8):945-50. https://doi.org/10.1002/art.1780340803 google scholar
  • 21. Baqi N, Moazami S, Singh A, Ahmad H, Balachandra S, Tejani A. Lupus nephritis in children: a longitudinal study of prognostic factors and therapy. J Am Soc Nephrol 1996;7(6):924-9. google scholar
  • 22. Lee HS, Choi Y. Clinical outcomes of childhood lupus nephritis: a single centre’s experience. Pediatr Nephrol 2007;22:222-31. https://doi.org/10.1007/s00467-006-0286-0 google scholar
  • 23. Al Salloum A. Cyclophosphamide therapy for lupus I. Odaman Al ve ark., Lupus Nefritli Çocuklarda İntravenöz Siklofosfamid Tedavisinin Etkinliğinin Değerlendirilmesi 83 nephritis poor renal survival in Arab children. Pediatr Nephrol 2003;18:357-61. google scholar
  • 24. Reinaldo M, Perira LJC, Santos ESC, Heonir R. Clinical effects of intermittent, intravenous cyclophosphamide in severe systemic lupus erythematosus. Nephron 1996;74(2):313-7. https://doi.org/10.1159/000189327 google scholar
  • 25. Das U, KV Dakshina Murty, Prasad N, Prayag A. Pulse cyclophospamide in severe lupus nephritis: Southern Indian Experience Saudi J Kidney Transpl. 2010;21(2):372-8. google scholar
  • 26. Yokoyama H, Wada T, Hara A, Yamahana J, Nakaya I, Kobayashi M, et al. The outcome and a new ISN/ RPS 2003 sınıfification of lupus nephritis in Japanese. Kidney Int 2004;66(6):2382-8. https://doi.org/10.1111/j.1523-1755.2004.66027.x google scholar
  • 27. Ayodele OE, Okpechi IG, Swanepoel CR. Predictors of poor renal outcome in patients with biopsy-proven lupus nephritis. Nephrology (Carlton) 2010;15(4):482-90. https://doi.org/10.1111/j.1440-1797.2010.01290.x google scholar
  • 28. Rush PJ, Baumal R, Shore A, Balfe JW, Schreiber M. Correlation of renal histology with outcome in children with lupus nephritis. Kidney Int 1986;24:1066–71. https://doi.org/10.1038/ki.1986.108 google scholar
  • 29. Dhir V, Aggarwal A, Lawrence A, Agarwal V, Misra R. Long term outcome of Lupus Nephritis in Asian Indians. Arthritis Care&Research 2012;64(5):713-20. https://doi.org/10.1002/acr.21597 google scholar
  • 30. Austin HA, Boumpas DT, Vaughan EM, Balow JE. High-risk features of lupus nephritis: importance of race and clinical and histological factors in 166 patients. Nephrol Dial Transplant 1995;10:1620-8. google scholar
  • 31. Gruppo Italiano Per Lo Studio Della Nefrite Lupica (GISNEL). Lupus nephritis: prognostic factors and probability of maintaining life-supporting renal function 10 years after the diagnosis. Am J Kidney Dis 1992;19:473-9. https://doi.org/10.1016/S0272-6386(12)80957-7 google scholar
  • 32. Rygg M, Pistorio A, Ravelli A, Maghnie M, Dilorgi N, Bader-Meunier B, et al. Paediatric Rheumatology International Trials Organisation (PRINTO) A longitudinal PRINTO study on growth and puberty in juvenile systemic lupus erythematosus. Ann Rheum Dis 2012;71: 511-7. https://doi.org/10.1136/annrheumdis-2011-200106 google scholar
  • 33. Appel GB, Cohen DJ, Pirani CL, Meltzer JI, Estes D. Long-term follow-up of patients with lupus nephritis. A study based on the sınıfification of the World Health Organization. Am J Med 1987;83(5):877-85. https://doi.org/10.1016/0002-9343(87)90645-0 google scholar
  • 34. Esdaile JM, Abrahamowicz M, MacKenzie T, Hayslett J, Kashgarian M. The time-dependence of long-term prediction in lupus nephritis. Arthritis Rheum 1994;37:359-68. https://doi.org/10.1002/art.1780370309 google scholar
  • 35. Naiker IP, Chrystal V, Randeree IG, Seedat YK. The significance of arterial hypertension at the onset of clinical lupus nephritis. Postgrad Med J 1997;73: 230-3. https://doi.org/10.1136/pgmj.73.858.230 google scholar
  • 36. Esdaile JM, Levington C, Federgreen W, Hayslett JP, Kashgarian M. The clinical and renal biopsy predictors of long-term outcome in lupus nephritis. Q J Med 1989;72:779-833. google scholar
  • 37. Al Salloum A. Cyclophosphamide therapy for lupus nephritis poor renal survival in Arab children. Pediatr Nephrol 2003;18:357-61. google scholar
  • 38. Mok CC, Ying KY, Nq WL, Lee KW, To CH, Lau CS, et al. Long-term outcome of diffuse proliferative lupus glomerulonephritis Treated with cyclophosphamide. The American Journal of Medicine 2006;119:25-33. https://doi.org/10.1016/j.amjmed.2005.08.045 google scholar
  • 39. Yang LY, Chen WP, Lin CY. Lupus nephritis in children-a review of 167 patients. Pediatrics 1994;94: 335-40. google scholar
  • 40. Font J, Cervera R, Espinosa G, Pallares L, RamosCasals M, Jimenez S, et al. Systemic lupus erythematosus (SLE) in childhood: analysis of clinical and immunological findings in 34 patients and comparison with SLE characteristics in adults. Ann Rheum Dis 1998;57:456-9. https://doi.org/10.1136/ard.57.8.456 google scholar
  • 41. Mosca M, Bencivelli W, Neri R, Pasquariello A, Batini V, Puccini R, et al. Renal flares in 91 SLE patients with diffuse proliferative glomerulonephritis. Kidney Int 2002;61:1502-9. https://doi.org/10.1046/j.1523-1755.2002.00280.x google scholar
  • 42. Moroni G, Pasquali S, Quaglini S, Banfi G, Casanova S, Maccario M, et al. Clinical and prognostic value of serial renal biopsies in lupus nephritis. Am J Kidney Dis 1999;34:530-9. https://doi.org/10.1016/S0272-6386(99)70082-X google scholar
  • 43. Al Salloum A. Cyclophosphamide therapy for lupus nephritis poor renal survival in Arab children. Pediatr Nephrol 2003;18:357-61. google scholar
  • 44. Dooley MA, Hogan S, Jennette C, Falk R. Cyclophosphamide therapy for lupus nephritis: poor renal survival in black Americans. Glomerular Disease Collaborative Network. Kidney Int 1997;51:1188-95. https://doi.org/10.1038/ki.1997.162 google scholar
  • 45. Huang JL, Lin CJ, Hung IJ, Luo SF. The morbidity and mortality associated with childhood onset systemic lupus erythematosus. Changgeng Yi Xue Za Zhi 1994; 17:113-20. google scholar
  • 46. Singh S, Devidayal, Kumar L, Joshi K. Mortality patterns in childhood lupus: 10 years’ experience in a developing country. Clin Rheumatol 2002;21:462-5. https://doi.org/10.1007/s100670200116 google scholar
  • 47. Lewis EJ, Hunsicker LG, Lan SP, Rohde RD, Lachin JM. A Controlled trial of plasmapheresis therapy in severe lupus nephritis. The New England Journal of Medicine 1992;326(21):1373-9. https://doi.org/10.1056/NEJM199205213262101 google scholar
  • 48. Dau PC, Callahan J, Parker R, Golbus J. Immunologic effects of plasmapheresis synchronized with pulse cyclophosphamide in systemic lupus erythematosus. J Rheumatol 1991;18:227-76. google scholar
  • 49. Yamaji K, Kim YJ, Tsuda H, Takasaki Y. Long-term Clinical outcomes of synchronized therapy with plasmapheresis and intravenous cyclophosphamide pulse therapy in the treatment of steroid-resistant lupus nephritis. Therapeutic Apheresis and Dialysis 2008;12(4): 298-305. https://doi.org/10.1111/j.1744-9987.2008.00591.x google scholar
  • 50. Danieli MG, Palmieri C, Salvi A, Refe MC, Strusi AS, Danieli G. Synchronized therapy and high-dose cyclophosphamide in proliferative lupus nephritis. J Clin Apher 2002;17:72-7. https://doi.org/10.1002/jca.10020 google scholar

Citations

Copy and paste a formatted citation or use one of the options to export in your chosen format


EXPORT



APA

Odaman Al, I., Emre, S., Bilge, I., Yılmaz, A., & Yavaş Aksu, B. (0001). Evaluation the Effectiveness of Intravenous Cyclophosphamide Treatment in Children with Lupus Nephritis. Journal of Child, 17(2), 77-83. https://doi.org/10.5222/j.child.2017.077


AMA

Odaman Al I, Emre S, Bilge I, Yılmaz A, Yavaş Aksu B. Evaluation the Effectiveness of Intravenous Cyclophosphamide Treatment in Children with Lupus Nephritis. Journal of Child. 0001;17(2):77-83. https://doi.org/10.5222/j.child.2017.077


ABNT

Odaman Al, I.; Emre, S.; Bilge, I.; Yılmaz, A.; Yavaş Aksu, B. Evaluation the Effectiveness of Intravenous Cyclophosphamide Treatment in Children with Lupus Nephritis. Journal of Child, [Publisher Location], v. 17, n. 2, p. 77-83, 0001.


Chicago: Author-Date Style

Odaman Al, Işık, and Sevinç Emre and Ilmay Bilge and Alev Yılmaz and Bağdagül Yavaş Aksu. 0001. “Evaluation the Effectiveness of Intravenous Cyclophosphamide Treatment in Children with Lupus Nephritis.” Journal of Child 17, no. 2: 77-83. https://doi.org/10.5222/j.child.2017.077


Chicago: Humanities Style

Odaman Al, Işık, and Sevinç Emre and Ilmay Bilge and Alev Yılmaz and Bağdagül Yavaş Aksu. Evaluation the Effectiveness of Intravenous Cyclophosphamide Treatment in Children with Lupus Nephritis.” Journal of Child 17, no. 2 (Oct. 2024): 77-83. https://doi.org/10.5222/j.child.2017.077


Harvard: Australian Style

Odaman Al, I & Emre, S & Bilge, I & Yılmaz, A & Yavaş Aksu, B 0001, 'Evaluation the Effectiveness of Intravenous Cyclophosphamide Treatment in Children with Lupus Nephritis', Journal of Child, vol. 17, no. 2, pp. 77-83, viewed 7 Oct. 2024, https://doi.org/10.5222/j.child.2017.077


Harvard: Author-Date Style

Odaman Al, I. and Emre, S. and Bilge, I. and Yılmaz, A. and Yavaş Aksu, B. (0001) ‘Evaluation the Effectiveness of Intravenous Cyclophosphamide Treatment in Children with Lupus Nephritis’, Journal of Child, 17(2), pp. 77-83. https://doi.org/10.5222/j.child.2017.077 (7 Oct. 2024).


MLA

Odaman Al, Işık, and Sevinç Emre and Ilmay Bilge and Alev Yılmaz and Bağdagül Yavaş Aksu. Evaluation the Effectiveness of Intravenous Cyclophosphamide Treatment in Children with Lupus Nephritis.” Journal of Child, vol. 17, no. 2, 0001, pp. 77-83. [Database Container], https://doi.org/10.5222/j.child.2017.077


Vancouver

Odaman Al I, Emre S, Bilge I, Yılmaz A, Yavaş Aksu B. Evaluation the Effectiveness of Intravenous Cyclophosphamide Treatment in Children with Lupus Nephritis. Journal of Child [Internet]. 7 Oct. 2024 [cited 7 Oct. 2024];17(2):77-83. Available from: https://doi.org/10.5222/j.child.2017.077 doi: 10.5222/j.child.2017.077


ISNAD

Odaman Al, Işık - Emre, Sevinç - Bilge, Ilmay - Yılmaz, Alev - Yavaş Aksu, Bağdagül. Evaluation the Effectiveness of Intravenous Cyclophosphamide Treatment in Children with Lupus Nephritis”. Journal of Child 17/2 (Oct. 2024): 77-83. https://doi.org/10.5222/j.child.2017.077



TIMELINE


Submitted18.12.2016
Accepted15.05.2017

LICENCE


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


SHARE




Istanbul University Press aims to contribute to the dissemination of ever growing scientific knowledge through publication of high quality scientific journals and books in accordance with the international publishing standards and ethics. Istanbul University Press follows an open access, non-commercial, scholarly publishing.