Childhood Kidney Diseases

Korean Society of Pediatric Nephrology (대한소아신장학회)
권호 표지
DOI QR코드

DOI QR Code

Clinicopathologic Changes in Children with Immunoglobulin A Nephritis and Henoch-Sch$\ddot{o}$nlein Purpura Nephritis after Cyclosporine A and Angiotensin-converting Enzyme Inhibitor Treatment

Immunuglobulin A 신질환과 Henoch-Schnlein purpura 신질환을 가진 소아에서의 cyclosporine A와 angiotensin-converting enzyme inhibitor 치료의 임상적, 병리학적 변화

  • Lee, Jeong Ju (Department of Pediatrics, Ajou University Hospital, Ajou Universtiy School of Medicine) ;
  • Kim, Yong-Jin (Department of Pathology, Yeungnam University College of Medicine) ;
  • Shin, Jae Il (Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine) ;
  • Yim, Hyunee (Department of Pathology, Ajou University Hospital, Ajou Universtiy School of Medicine) ;
  • Park, Se Jin (Department of Pediatrics, Ajou University Hospital, Ajou Universtiy School of Medicine)
  • 이정주 (아주대학교 의과대학 소아청소년과) ;
  • 김용진 (영남대학교 의과대학 병리학과) ;
  • 신재일 (연세대학교 의과대학 소아청소년과) ;
  • 임현이 (아주대학교 의과대학 병리학과) ;
  • 박세진 (아주대학교 의과대학 소아청소년과)
  • Received : 2013.09.27
  • Accepted : 2013.10.14
  • Published : 2013.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: To investigate the clinicopathologic effects of cyclosporine A (CsA) in children with diseases characterized by mesangial immunoglobulin A deposits such as immunoglobulin A nephropathy (IgAN) and Henoch-Sch$\ddot{o}$nlein purpura nephritis (HSPN). Methods: We retrospectively reviewed the clinicopathologic outcomes of 54 children (IgAN, 36; HSPN, 18) treated with CsA. The starting dose of CsA was 5 mg/kg per day, and it was administered in 2 divided doses. The degree of proteinuria and pathologic changes in renal biopsies were evaluated before and after CsA treatment. Results: The mean protein to creatinine ratio decreased from $3.7{\pm}1.5$ to $0.6{\pm}0.4$(P <0.001), and 32 (59.2%) children achieved complete remission of proteinuria after 1-year CsA treatment. Among the 54 children, 24 maintained normal renal function and 25 exhibited microscopic hematuria or proteinuria at the end of CsA treatment. In the HSPN group, 3 children whose initial biopsies indicated class IIIb disease showed class II disease on follow-up, and the follow-up biopsies of 2 children who had class II disease indicated the same class II disease. In the IgAN group, cortical tubular atrophy occurred in 1 child, and no child with IgAN had cortical interstitial fibrosis or tubular atrophy after 1-year CsA treatment. No significant complications were found in the children treated with CsA. Conclusion: Our findings indicate that CsA treatment is effective and beneficial in reducing massive proteinuria and preventing progression to end-stage renal failure in children with glomerular diseases characterized by IgA deposits, such as IgAN and HSPN, within 1 year of treatment.

목적: IgA 신병증, HSP 신병증은 사구체의 메산지움에 IgA가 침착되는 대표적인 질환이다. 본 연구는 소아에서, 이 두 가지 질환에 대한 Cyclosporin A 의 임상적 및 병리학적 효과를 평가하기 위하여 시행되었다. 방법: 총 54명의 환자(IgA 신병증: Henoch-Sch$\ddot{o}$nlein purpura 신병증=36:18)를 대상으로 후향적으로 연구를 진행하였다. CsA는 5mg/kg/day 으로 투여하였으며, 투여 전, 후로 단백뇨의 양을 측정, 병리학적 변화를 조사하기 위해 신생검을 시행하였다. HSP 신병증 및 IgA 신병증의 신생검은 병리학적으로 각각 ISKDC 분류법, Oxford 분류체계(2009)로 구분하였다. 결과: 혈청 단백/크레아티닌 비는 치료 전후로 $3.7{\pm}1.5$에서 $0.6{\pm}0.4$으로 호전되었고(P<0.001), 총 54명 중 32명의 환자(59.2%)에서 CsA 치료 1년 후 단백뇨의 관해를 보였다. 신생검의 병리학적 소견은 호전되거나, 또는 치료 전후로 유지되는 양상을 보였으며, CsA로 인한 합병증은 없었다. 결론: CsA 는 IgA의 사구체 침착을 특징으로 하는 IgA 신병증, HSP 신병증 환자에서 단백뇨 감소효과 및 말기신부전으로의 진행을 예방하는 데에 효과적인 것으로 사료된다.

Keywords

References

  1. Donadio JV, Grande JP. IgA nephropathy. N Engl J Med 2002; 347:738-48. https://doi.org/10.1056/NEJMra020109
  2. D'Amico G. Natural history of idiopathic IgA nephropathy: role of clinical and histological prognostic factors. Am J Kidney Dis 2000;36:227-37. https://doi.org/10.1053/ajkd.2000.8966
  3. Katafuchi R, Vamvakas E, Neelakantappa K, Baldwin DS, Gallo GR. Microvascular disease and the progression of IgA nephropathy. Am J Kidney Dis 1990;15:72-9. https://doi.org/10.1016/S0272-6386(12)80595-6
  4. Ozen S, Ruperto N, Dillon MJ, Bagga A, Barron K, Davin JC, et al. EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides. Ann Rheum Dis 2006;65: 936-41.
  5. Koutkia P, Mylonakis E, Rounds S, Erickson A. Leucocytoclastic vasculitis: an update for the clinician. Scand J Rheumatol 2001;30:315-22. https://doi.org/10.1080/030097401317148499
  6. Davin JC, Weening JJ. Henoch-Schönlein purpura nephritis: an update. Eur J Pediatr 2001;160:689-95.
  7. Lee TH, Lee EY, Cho YS, Yoo B, Moon HB, Lee CK. Concurrent occurrence of chylothorax and chylous ascites in a patient with Henoch-Schonlein purpura. Scand J Rheumatol 2003; 32:378-9. https://doi.org/10.1080/03009740410005070
  8. Kaku Y, Nohara K, Honda S. Renal involvement in Henoch-Schonlein purpura: a multivariate analysis of prognostic factors. Kidney Int 1998;53:1755-9. https://doi.org/10.1046/j.1523-1755.1998.00915.x
  9. Ronkainen J, Ala-Houhala M, Huttunen NP, Jahnukainen T, Koskimies O, Ormälä T, et al. Outcome of Henoch-Schoenlein nephritis with nephrotic-range proteinuria. Clin Nephrol 2003;60:80-4. https://doi.org/10.5414/CNP60080
  10. Counahan R, Winterborn MH, White RHR, Heaton JM, Meadow SR, Bluett NH, et al. Prognosis of Henoch-Schönlein nephritis in children. Br Med J 1977;2:11-4 https://doi.org/10.1136/bmj.2.6078.11
  11. Working Group of the International IgA Nephropathy Network and the Renal Pathology Society, Cattran DC, Coppo R, Cook HT, Feehally J, Roberts IS, et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int 2009;76:534-45. https://doi.org/10.1038/ki.2009.243
  12. Working Group of the International IgA Nephropathy Network and the Renal Pathology Society, Roberts IS, Cook HT, Troyanov S, Alpers CE, Amore A, et al. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int 2009;76:546-56. https://doi.org/10.1038/ki.2009.168
  13. Shin JI, Lim BJ, Kim PK, Lee JS, Jeong HJ, Kim JH. Effects of cyclosporin A therapy combined with steroids and angiotensin converting enzyme inhibitors on childhood IgA nephropathy. J Korean Med Sci 2010;25:723-7. https://doi.org/10.3346/jkms.2010.25.5.723
  14. Park JM, Won SC, Shin JI, Yim H, Pai KS. Cyclosporin A therapy for Henoch-Schonlein nephritis with nephrotic-range proteinuria. Pediatr Nephrol 2011;26:411-7. https://doi.org/10.1007/s00467-010-1723-7
  15. Shin JI, Park JM, Shin YH, Kim JH, Lee JS, Jeong HJ. Henoch-Schonlein purpura nephritis with nephrotic-range proteinuria: histological regression possibly associated with cyclosporin A and steroid treatment. Scand J Rheumatol 2005;34:392-5. https://doi.org/10.1080/03009740510026544
  16. Egido J, Sancho J, Mampaso F, Lopez Trascasa M, Sanchez Crespo M, Blasco R, et al. A possible common pathogenesis of the mesangial IgA glomerulonephritis in patients with Berger's disease and Schonlein-Henoch syndrome. Proc Eur Dial Transplant Assoc 1980;17:660-6.
  17. Waldo FB. Is Henoch-Schonlein purpura the systemic form of IgA nephropathy? Am J Kidney Dis. 1988;12:373-7.
  18. Levy M. Familial cases of Berger's disease and anaphylactoid purpura: more frequent than previously thought. Am J Med 1989;87:246-8.
  19. Montoliu J, Lens XM, Torras A, Revert L. Henoch-Schonlein purpura and IgA nephropathy in father and son. Nephron 1990;54:77-9. https://doi.org/10.1159/000185813
  20. Thorner PS, Farine M, Arbus GS, Poucell S, Baumal R. IgA nephropathy: Henoch-Schonlein purpura and Berger's disease in one patient. Int J Pediatr Nephrol 1986;7:131-6.
  21. Chishiki M, Kawasaki Y, Kaneko M, Ushijima Y, Ohara S, Abe Y, et al. A 10-year-old girl with IgA nephropathy who 5 years later developed the characteristic features of Henoch-Schonlein purpura nephritis. Fukushima J Med Sci 2010;56: 157-61. https://doi.org/10.5387/fms.56.157
  22. Meadow SR, Scott DG. Berger disease: Henoch-Schonlein syndrome without the rash. J Pediatr 1985;106:27-32. https://doi.org/10.1016/S0022-3476(85)80459-5
  23. Rai A, Nast C, Adler S. Henoch-Schonlein purpura nephritis. J Am Soc Nephrol 1999;10:2637-44.
  24. D'Amico G. Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome. Semin Nephrol 2004;24:179-96. https://doi.org/10.1016/j.semnephrol.2004.01.001
  25. Jardim HM, Leake J, Risdon RA, Barratt TM, Dillon MJ. Crescentic glomerulonephritis in children. Pediatr Nephrol 1992; 6:231-5. https://doi.org/10.1007/BF00878354
  26. Niaudet P, Habib R. Methylprednisolone pulse therapy in the treatment of severe forms of Schönlein-Henoch purpura nephritis. Pediatr Nephrol 1998;12:238-43. https://doi.org/10.1007/s004670050446
  27. Shin JI, Park JM, Shin YH, Kim JH, Lee JS, Kim PK, et al. Can azathioprine and steroids alter the progression of severe Henoch-Schonlein nephritis in children? Pediatr Nephrol 2005;20:1087-92. https://doi.org/10.1007/s00467-005-1869-x
  28. Yoshikawa N, Ito H, Sakai T, Takekoshi Y, Honda M, Awazu M, et al. A controlled trial of combined therapy for newly diagnosed severe childhood IgA nephropathy. The Japanese Pediatric IgA Nephropathy Treatment Study Group. J Am Soc Nephrol 1999;10:101-9.
  29. Lai KN, Mac-Moune Lai F, Vallance-Owen J. A short-term controlled trial of cyclosporine A in IgA nephropathy. Transplant Proc. 1988;20(3 Suppl 4):297-303.
  30. Borel JF. Pharmacology of cyclosporine (sandimmune). IV. Pharmacological properties in vivo. Pharmacol Rev 1990;41: 259-371.
  31. Wiegmann TB, Sharma R, Diederich DA, Savin VJ. In vitro effects of cyclosporine on glomerular function. Am J Med Sci 1990;299:149-52. https://doi.org/10.1097/00000441-199003000-00001
  32. Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz S, Delfgaauw J, et al. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med 2008;14:931-8. https://doi.org/10.1038/nm.1857
  33. Seikaly MG, Prashner H, Nolde-Hurlbert B, Browne R. Long-term clinical and pathological effects of cyclosporin in children with nephrosis. Pediatr Nephrol 2000;14:214-7. https://doi.org/10.1007/s004670050044
  34. Iijima K, Hamahira K, Tanaka R, Kobayashi A, Nozu K, Nakamura H, et al. Risk factors for cyclosporine-induced tubulointerstitial lesions in children with minimal change nephritic syndrome. Kidney Int 2002;61:1801-5. https://doi.org/10.1046/j.1523-1755.2002.00303.x
  35. Kengne-Wafo S, Massella L, Diomedi-Camassei F, Emma F. Idiopathic membranous nephropathy associated with polycystic kidney disease. Pediatr Nephrol 2010;25:961-3. https://doi.org/10.1007/s00467-009-1398-0
  36. Hausberg M, Barenbrock M, Hohage H, Müller S, Heidenreich S, Rahn K-H. ACE inhibitor versus beta-blocker for the treatment of hypertension in renal allograft recipients. Hypertension 1999;33:862-8. https://doi.org/10.1161/01.HYP.33.3.862