1. Journal Reading 2006-10-13 Present by Dr. 陳志榮

2. The Banff 97 Working Classification of Renal Allograft Pathology Racusen LC, Solez K, Colvin RB, Bonsib SM, Castro MC, Cavallo T, Croker BP, Demetris AJ, Drachenberg CB, Fogo AB, Furness P, Gaber LW, Gibson IW, Glotz D, Goldberg JC, Grande J, Halloran PF, Hansen HE, Hartley B, Hayry PJ, Hill CM, Hoffman EO, Hunsicker LG, Lindblad AS, Yamaguchi Y, et al. Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. lracusen@welchlink.welch.jhu.edu ~ kidney International,55(2),1999, 713-23

3. Introduction Standard interpretation to guide therapy and clinical trials. Banff schema and Collaborative Clinical Trials in Transplantation (CCTT)

4. Method and Materials Analysis of data using Banff classification. Publication of and experience of the CCTT modification. International conferences. Data from recent studies of impact of vasculitis on transplant outcome.

6. Result Specimen adequacy. Semiquantitative method. Actue/active lesion scoring.  Tubulitis, intimal arteritis, interstitial inflammation, glomerulitis. Chronic/sclerosing lesion scoring.  Interstitial fibrosis, tubular atrophy, allograft glomerulopathy, mesangial matrix increase.

7. Actue/active lesion scoring

8. Intimal artertitis: Lymphocytic infiltration beneath the endothelium. Arteritis: Inflammation in the media and/or with fibrinoid necrosis of vessel wall.

9. Actue/active lesion scoring

13. Chronic/sclerosing lesion scoring

18. Arteriolar hyaline change (nodular) : Cyclosporine or FK506 toxicity. Separate from chronic vascular change. Arteriolar hyalinosis (ah) score

19. Discussion Historical review Finkelstein et al.,1976 (pre- cyclosporine era). Banfi et al. Matas et al., 1983 Banff classification,1991 (Banff 93)

20. Discussion Vasculitis in renal allograft: Poorer response to therapy and/or outcome. Intimal arteritis ± fibrinoid necrosis. Roche mycophenolate mofetil study: 87 biopsies=> allograft loss rate. Nickeleit et al: less responsive to steroid.

21. Discussion Interstitial inflammation I2t2 for diagnosis of rejection is likely appropriate. Rush et al.: 1/3 asmptomatic patient (subclinical rejection) had i2t2 lesions with a less than 10% change in serum creatinine but had good treatable response. borderline rejection i1t1 i1t2=>? Significance for rejection.  Correlate with clinical finding.  With decreased function=>therapay.  With stable function=> no therapy.

22. Discussion Antibody-mediated component Widespread endothelial injury. Fibrinoid changes of vessel wall. Glomerular and small vessel thromboses. Infarctions. Glomerulitis. Polymorphonuclear leukocytes in peritubular capillaries.

23. Discussion Other disease processes Polymorphonuclear leukocyte (PMNL) in interstitium and tubular lumina.  Aucte bacterial infection. PMNL in peritubular and glomerular capillaries.  Severe acute endothelial injury and possible antibody-mediated rejection. Eosinphils.  Hypersensitivity reaction.

24. Discussion Viral infection Megalic cells, nuclear smudging, intranuclear or cytoplasmic inclusions. Cytomegalovirus, polyoma virus, adenovirus etc. Colvin: relatively severe tubular cell injury and mild inflammation raises the possibility.

25. Discussion Post-transplant lymphoproliferative disorder (PTLD) Immunoblasts, plasma cell, large cleaved/noncleaved cells and small round lymphocyte. Nuclear atypia, EBV association, B cell preponderant. D/D: rejection.

26. Discussion Cyclosporine Tubular vacuolization. Microvascular toxicity: glomerular and arterioles.

27. Discussion Diagnosis==>prediction of allograft function and outcome. Early intervention. Molecular study.

28. How to handle the renal transplant biopsy D’Agati, Jennette,Silva edn.Non-neoplastic kidney diseases, Atlas of non-tumor pathology, first series, fascicle 4, 2005,p668

29. Materials: Two cores of tissue.  focal in early stages Glomeruli: ≧ 10 Arteries ≧ 2

30. Processing: Majority of specimen.  Light microscopic examination. (as renal biopsy routine) Small portion.  immunofluorescence study. EM examination.  not general reserved.

31. Light microscopic examination Three H&E slides. Three PAS or silver stained slides.  Glomerulitis or tubulitis, arteriolar hyaline, double contours of glomerular capillaries. One Masson trichrome stained slide.  Interstitial fibrosis. Each section:3-4 microns.

32. Immunofluorescence study: C4d: routine use to exclude acute humoral rejection. ? Full panel in early transplant perioid.  IgM, IgG, IgA, C3,C1q,fibrinogen, kappa and lambda light chain.

33. Rapid processing: Same day. Formalin-fixed. Frozen section is less reliable.

34. Allograft renal transplant routine protocol in WanFang Hospital.

35. Thank you for your attention!