Infection after renal transplantation

1.分成三個時期#

• Post-transplantation 1M
  • 此時期感染如一般術後人nosocomial infection(bacteria>fungus)一樣(和HSCT不一樣免疫力沒有很差)
    • Pneumonia, UTI, wound infection, CRBSI…)
• Post-transplantation 1M-6M
  • 此時期感染是一些T cell dysfunction的感染
    • HSV, VZV, EBV, CMV, HBV, HCV, BK(BK nephropathy range大：D6~5yrs皆可, mean:1 yr), cryptococcus, PJP, Nocardia, TB, Listeria, Toxoplasma
    • CMV 預防(valganciclovir 900mg/d): D+/R− 給 6 個月; R+ 部分中心給 3 個月或 pre-emptive 監測; 「HSV/VZV 預防」是 valacyclovir(acyclovir 家族), 非 Valcyte
    • 也有些人作法是監測CMV viral load with pre-emptive Tx, 兩者cost and 效果都差不多
    • HBV: 術前評估 HBsAg/anti-HBc; HBsAg(+)者先 NA(entecavir/TDF)預防再移植; anti-HBc(+) donor 可傳播→recipient 追蹤 HBV DNA; 未免疫者術後補打疫苗(HBV(+) recipient 用 HBIG＋NA)
    • BK virus是會監測plasma viral DNA Q1M for 6M, then 9M, 12M, 18M, 24M…(2024 國際共識指引：每月篩檢至第 9 個月，之後每 3 個月至第 2 年；持續 >1,000 或 >10,000 copies/mL 啟動階梯式減藥：先減代謝拮抗劑 MMF/AZA 50% 至停用，再調降 CNI 25-50%〔PMID 38605438〕)

      "We recommend screening all kidney transplant recipients for plasma BKPyV-DNAemia monthly until 9 months posttransplantation, and every 3 months until 2 years... Stepwise immunosuppression reduction should be initiated when plasma BKPyV-DNA is persistently >1,000 copies/mL or exceeds 10,000 copies/mL." (Hirsch HH, et al. Transplantation 2024; PMID 38605438)

• Cryptococcus無常規監測(僅臨床懷疑時查 CRAG)
• 所以會吃Baktar for ≥6M(PJP, Toxoplasma, Nocardia, listeria, UTI)
• 若之後有再用ATG or steroid pulse therapy, 應考慮再用Baktar and Valcyte
• Post-transplantation >6M
  • 一般社區感染與一些T cell dysfunction的感染(milder and less; 不過時常在acute rejection要用strong immunosuppression者另當別論)
    • Pneumonia, UTI
    • HSV, EBV(PTLD), CMV(大多是retinitis or GI involvement), HBV, HCV, BK, JC(PML), HPV(skin cancer), Aspergillus, Mucormycosis, Nocardia, TB

2.預防策略速查表(依 D/R 血清狀態)#

• UTI: 移植後第一個月(導尿管)與 1-6M 為高峰; 反覆 UTI 需檢查吻合口/結石/神經性膀胱

3.CMV 治療劑量速查#

• Induction 治療: IV ganciclovir 5mg/kg Q12h(依腎功能調整) 或 oral valganciclovir 900mg BID; disease/severe 者 IV 至改善後轉口服, 總療程至 viral load(-)再 +2W(至少 2-4W)
• 減免疫抑制: 先減 anti-metabolite(MMF/AZA)
• 抗藥性(ganciclovir-resistant, UL97/UL54 mutation)處置詳見下述2020s新藥段(foscarnet 注意腎毒性/Mg/K)
• 預防用藥不耐受(白血球低): letermovir(terminase inhibitor; JAMA 2023; PMID 37279999)：在 CMV D+/R− 高風險成人腎移植受者中，口服 Letermovir 預防至術後第 28 週非劣於 Valganciclovir，且顯著降低白血球減少症（Leukopenia 11.3% vs 37.0%）與嗜中性球減少症發生率。

  "Among adult kidney transplant recipients at high risk for CMV (D+/R-), letermovir was noninferior to valganciclovir for the prevention of CMV disease through week 52, with a significantly lower incidence of leukopenia or neutropenia (26% vs. 64%)." (Limaye AP, et al. JAMA 2023; PMID 37279999)

4.For PJP#

• 菌量沒HIV Pt那麼高, 所以test的sensitivity較低, 若test(-), 臨床仍高度懷疑應做lung tissue biopsy
• 治療一樣是Baktar; no evidence of use higher dosage of steroid in renal transplant Pts with PJP; AST指引(Clin Transplant 2019; PMID 31077616)：PJP 高危因子包括淋巴球低下、CMV感染、低丙種球蛋白血症、類固醇/排斥治療及年齡>65歲，常規預防建議至少 6-12 個月〔PMID 31077616〕
• For CMV
  • Infection: evidence of replicating virus
  • Disease: End organ disease + 當處有virus
    • Syndrome: Viremia + S/S(fever, cytopenia(多thrombocytopenia因為cross reaction of anti-CMV Ab and PLT) +/- neutropenia +/- anemia))
  • Transmitted by body fluid(including breast milk) and blood(所以CMV(+)的donor可以傳染給CMV(-)recipient?)
  • 小心雖然大多數CMV disease會有Viremia, 不過retinitis or GI tract involvement不一定有viremia
  • General Tx
    • 
      • 若要↓immunosuppressions, 多先↓anti-metabolites(和BK nephropathy作法類似)
      • For non-life-threatening CMV infection, oral Valcyte不輸給IV form
        • 不過CMV syndrome, severe CMV disease(retinitis, CNS, pneumonitis, colitis) 建議先使用IV form
      • Tx duration
        • 看疾病severity, 越嚴重治越久且考慮followed by prophylactic dose(療程原則同§3 induction段：viral load(-)後再+2W)
          • 2020s新藥: letermovir(CMV terminase inhibitor; Letermovir vs Valganciclovir(JAMA 2023; PMID 37279999)：D+/R−預防非劣於 valganciclovir 且 leukopenia/neutropenia 較少〔PMID 37279999〕)→valganciclovir不耐受/白血球低者適用; maribavir 400mg BID(Maribavir SOLSTICE(Clin Transl Sci 2024; PMID 38071422)：第8週 CMV 清除優於 investigator-assigned therapy〔PMID 38071422〕)用於難治/抗藥性CMV(含ganciclovir/valganciclovir resistant)
    • Leflunomide
      • Targets viral capsid assembly(another mechanism)
      • Less potential for the cross-resistance
      • 也有人用在BK nephropathy(不過CMV證據較夠)