Withdraw of immunosuppression after renal graft failure

Transplant約 6 分鐘3 個章節

1.Reasons for withdraw#

increased risk of infection, malignancy(kaposi's sarcoma(HHV8), NHL(EBV), skin cancer(HPV), melanoma(?)...), CVD, steroid toxicity under immunosuppression

2.Complications of immunosuppressions withdraw#

Graft rejection/inflammation變很厲害(chronic inflammatory syndrome), 甚至需要nephrectomy(文獻:graft failure 後 nephrectomy 比例各系列差異大, 約 20-60%, 較早期/用 CsA 時代之報告偏高; FK506 時代較低)
- Indication for nephrectomy
  - S/S(graft intolerance syndrome): fever, hematuria, graft pain, localized edema, infection; chronic inflammation可BWL, fatigue, EPO resistance, GI/neurologic disturbance
  - Early graft failure/loss(failure within 1yr after transplantation)→ 見§3 early failure段
  - 是否所有人都要nephrectomy來減少chronic inflammation進而減少morbidity/mortality：無併發症之慢性移植腎衰竭多數不需常規切除(AN)，尚無明確證據顯示改善預後，主要保留給早期手術技術性失敗或有症狀之感染、惡性腫瘤、graft intolerance syndrome (GIS)〔PMID 37122077〕
  - 若發生graft rejection after withdraw:consider 5-7天 prednisone 0.3-1mg/kg/day then nephrectomy
  - 不適合手術者之替代: transplant renal artery angioembolization(graft 栓塞術)——可控制 graft intolerance/出血/頑固性 HTN, 併發症為 post-embolization syndrome(疼痛/發燒)、感染風險
  - 加速撤藥情境: 危及生命併發症(重症感染、惡性腫瘤、TMA)時應快速停藥而非常規 taper
  - 註:other indication for allograft nephrectomy(不干immunosuppressions的事)
    - Allograft rupture
    - Infarction due to thrombosis(持續發燒/疑似感染源者考慮切除或栓塞)
    - Emphysematous pyelonephritis
Become more sensitized(可能影響下次transplantation；停藥後 sensitization 顯著上升，GIS 組在症狀出現時即達高峰〔PMID 25297845〕)
- 註:nephrectomy 本身亦會因手術發炎反應、停藥伴隨之腎衰竭及殘留血管內皮而增加致敏風險(increased sensitization)〔PMID 37122077〕；單中心回溯研究（Transplant Direct 2022; PMID 36518791）：停用免疫抑制劑者致敏顯著上升（cPRA 中位數 18%→96%），而維持免疫抑制與病患死亡率或再移植成功率皆無顯著相關。
  
  "Maintaining immunosuppression was not associated with mortality or retransplantation, but was associated with reduced sensitization (discontinuing immunosuppression resulted in a marked rise in cPRA from median 18% to 96%)." (Chinnakotla S, et al. Transplant Direct 2022; PMID 36518791)
More rapid residual graft functional loss
Secondary adrenal insufficiency after steroid withdraw
- S/S:persistent fever, weakness, myalgias, arthralgias, weight loss with subsequent fluid overload(透析病人水分移除能力下降而表現出來), mild hypercalcemia, and eosinophilia
- Consider ACTH stimulation test and insulin tolerance test
- 怎麼taper steroid要看duration/dosage of steroid, 病人狀況, test結果; 沒有很好的定論

3.Withdraw(no consensus method; below as British Transplantation Society Guidelines)#

KDIGO 2023 爭議會議原則(Kidney Int 2023; PMID 37236357): 停藥與否應依個別病人風險效益分析與數月內再移植的可能性決定；且強調進入透析前應提早建立血管通路(dialysis-access readiness)，避免使用 CVC〔PMID 37236357〕

"Dialysis-access readiness should be prioritized before resumption of dialysis, avoiding the use of central venous catheters whenever feasible... The decision to continue or taper immunosuppression after allograft failure should be individualized, balancing the risks of sensitization against the risks of infection and malignancy." (Josephson MA, et al. Kidney Int 2023; 104(6):1076-1091. PMID: 37236357)
Early allograft failure(failure within 1yr after transplantation): immediate withdrawal of immunosuppression combined with preemptive nephrectomy
Later allograft failure without residual renal function:immediately withdraw CNI/AZA/MMF; taper prednisone 1mg/month, 小心graft rejection and secondary adrenal insufficiency S/S
- 如果allograft仍有residual function:DC anti-metabolite(MMF/AZA); change CNI to QD(=減半?), then taper over 3-6M; change Prednisone to 5mg QD then taper over 3-6M(所以一樣1mg/month?)
  - 減量期間監測: 每月 graft tenderness/發燒/尿量、Cre(殘餘功能者)、感染與腫瘤徵象; DSA 上升或 intolerance S/S → 加速停藥並考慮 nephrectomy/栓塞
  - 感覺有點類似BK nephropathy的taper法...
若一年內要second renal transplantation:不taper