Rejection or Not? Interhospital Renal Meeting 10 Oct Desmond Yap & Sydney Tang Queen Mary Hospital

Transcription

1 Rejection or Not? Interhospital Renal Meeting 10 Oct 2007 Desmond Yap & Sydney Tang Queen Mary Hospital

2 Case Presentation F/61 End stage renal failure due to unknown cause Received HD in private hospital for 3 months Cadaveric renal transplant in China in 1990 Immunosuppression with cyclosporin A and steroids

3 Case Presentation Best serum Cr after discharge was 90 umol/l and remained stable until Jun 2007 Noted asymptomatic rise in serum Cr over 6 months Denied any intake of herbs/ NSAIDs/ / OTC drugs

4 /1/07 23/2/07 23/3/07 23/4/07 23/5/07 23/6/07 23/7/07 23/8/07 23/9/07 Serum Creatinine Level

5 What are the differential diagnoses?

6 Common causes of late allograft failure Infection with or without anatomic anomaly e.g. reflux (bacterial, viral, etc) Late acute rejection Drugs (CNI toxicity, other nephrotoxic agents e.g. NSAIDs,, herbs, OTC drugs, P450 inducers without CNI dose adjustments, contrast) Recurrent or de novo GN Obstructive lesions Chronic allograft nephropathy Transplant renal artery stenosis Malignancy / PTLD Noncompliance Death with functioning graft (e.g. from CVD)

7 Case Presentation Serum Cr up to 516 umol/l CyA (C-0): 92 ng/ml (her usual level) Physical examination: Afebrile BP 187/90 mmhg No graft tenderness No graft bruit

8 Case Presentation MSU: WCC+; RBC <3/uL ul; ; granular casts+ CMV pp65 negative USG/doppler graft kidney: swollen graft, mild increase in resistive index, no hydronephrosis/sol

9 What will you do next?

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11 What is the diagnosis? Rejection or not

12 Case Presentation Allograft renal biopsy performed: crescentic GN involving 80% of glomeruli,, no tubulitis suggestive of rejection, C4d staining -ve IF and EM pending

13 What further Ix is needed?

14 Case Presentation ANF 1/80 C3 77 Pattern Homogenous C4 20 AntidsDNA Negative RF <12

15 Case Presentation IgG 553 Anti-GBM <2 IgA 192 ANCA Negative IgM 125 ASOT <200 Cryoglobulin Negative

16 How should one treat?

17 47 yo man with ESRD Cad Tx 1 year later 10 mo after Tx,, developed ARF Bx: crescentic nephritis Steroid stepped up and AZA replaced by MMF but no improvement in graft fx Benabdallah L et al. AJKD 2002

18 Case Presentation Given IV methylprednisolone and IV cyclophosphamide Developed APO and given IV lasix Noted uremic symptoms with progression of serum Cr Required urgent HD support

19 Case Presentation Underwent plasmapheresis Maintained on oral prednisolone and low dose oral cyclophosphamide Serum Cr now remained static at around 550 umol/l

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22 Case presentation IF: predominant mesangial IgA deposition Electron microscopy: electron dense deposits over the mesangium Imp: de novo crescentic IgAN in graft kidney

23 Crescentic IgAN in the allograft kidney

24 Crescentic IgAN in post renal transplant patients Recurrent vs. De novo IgAN One case series in Seattle reported 33 cases of crescentic GN between 1989 and 2003 among 2959 allograft biopsy; 8 of these cases were due to recurrent or de novo IgAN Microscopic hematuria, proteinuria,, rise in serum creatinine Kowalewska J et al. Am. J Kidney Dis 2005

25 Crescentic IgAN in post renal transplantation Average crescent involvement ~52% Can occur late after transplantation (1.75 to 20 years) Poor prognosis despite treatment Poor response to therapy (plasmapheresis( plasmapheresis/ / IV steroids) Most returned to dialysis Kowalewska J et al. Am. J Kidney Dis 2005

26 Renal Transplant in IgAN at QMH 542 renal transplants between patients (13.8%) had IgAN as the primary disease for ESRF 14 (18.7%) of the 75 patients had recurrent IgAN Diagnosed as 67.7+/-11 months post transplantation Choy BY et al. Nephrol Dial Transplant 2003

27 Renal Transplant in IgAN at QMH Graft failure occurred in 5 (35.7%) of the 14 patients (3 due to IgAN and 2 related to chronic rejection) Three (4.9%) of the 61 patients without recurrent IgAN had graft failure, all due to chronic rejection. Graft survival was similar between living-related and cadaveric/living /living-unrelated patients (12-year graft survival, 88 and 72%, respectively, P = 0.616).

28 Renal Transplant in IgAN at QMH Renal allograft survival within the first 12 years was better in patients with primary IgAN compared with those with other primary diseases (80 vs 51%, P = 0.001) Thereafter, IgAN patients showed an inferior graft survival (74 vs 97% in non- IgAN patients, P = 0.001).

29 De novo crescentic IgAN post renal transplantation Case report from Japan: 46 y.o. man with DMN who received cadaveric renal transplant subsequently developed RPGN with mesangial IgA deposits? IgAN/HSP, leading to graft failure and resumption of RRT Shimizu T et al. Clin Transplant 2001

30 Crescentic IgAN in renal transplant Significantly greater chance of graft loss 57% in those with crescents and 20% in those without crescents Kowalewska J et al. Am. J Kidney Dis 2005

31 Crescentic GN in post renal transplantation Infection related? Fungal infection Egbuna O et al. Am. J Kidney Dis 2007

32 First reported case of renal candidiasis causing crescentic Gn 22 yo, white female Day 38 post-tx biopsy, x 40 Graft nephrectomy Grocott-methenamine-silver stain, x 40 AJKD 2007

33 Crescentic GN in post renal transplantation Infection related? Fungal infection Egbuna O et al. Am. J Kidney Dis 2007 CMV infection Detwiler RK et al. Am J Kidney Dis 1998 Infective endocarditis Lionel A et al. Transplantation 1998

34 Crescentic IgAN post renal transplant Case report of post-reperfusion injury Graft IgAN with severe atherosclerosis of iliac artery Developed RPGN after axillo-femoral bypass Postulation Enhancement of capillary damage, inflammation and oxidative stress Presence of IgAN immune deposits increase oxidative stress Tovbin D et al. J. Nephrol 2004

35 Treatment De novo IgAN,, steroid with/without cyclophosphamide leads to reduction in proteinuria but not improvement in serum Cr Recurrent or de novo crescentic GN required ACEI/ARB + intensification of immunosuppression Carneiro-Roza F et al. Transplant Proc. 2006

36 Treatment Good results with IV+ oral steroids, with or without cyclophosphamide when <50% glomerulus with crescents >50% crescents but initial SCr <2.5mg/dL Carneiro-Roza F et al. Transplant Proc. 2006

37 Questions?

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39 Acknowledgement Department of Pathology, QMH