帶狀皰疹疫苗對於慢性腎臟病患者之腎臟保護成效評估:一項基於TriNetX多中心資料庫之研究

研究背景：慢性腎臟病（CKD）患者因尿毒環境與病程進展，常伴隨程度不一的免疫調控受損與慢性炎症，使其罹患帶狀皰疹（HZ）及其相關併發症的風險顯著增加。帶狀皰疹發作後引發的系統性炎症與內皮細胞損傷，已被證實會加速CKD患者進展至末期腎臟病（ESRD）。然而，帶狀皰疹疫苗接種在臨床上是否具有延緩腎功能惡化之腎臟保護成效，目前仍缺乏直接的實證醫學證據。研究方法及資料：本研究利用TriNetX美國合作網絡（U.S. Collaborative Network）全球電子病歷資料庫進行一項回溯性世代研究。研究納入2012年至2024年間、年齡滿50歲（含）以上且診斷為慢性腎臟病（第1至5期或未指明分期）的成年患者。排除指標日期前已確診ESRD、有帶狀皰疹病史或處於嚴重免疫抑制狀態者。研究將接種帶狀皰疹疫苗（含活性減毒疫苗Zostavax或重組次單位疫苗Shingrix）的患者，與未接種之對照組進行1:1的傾向評分配對（Propensity Score Matching），以控制年齡、性別、種族、共病症及用藥紀錄等混淆變項。主要研究結局為ESRD進展（定義為進展至CKD第5期、開始長期透析或接受腎臟移植）。使用Cox比例風險模型評估調整後風險比（Hazard Ratio, HR）與95%信賴區間（Confidence Interval, CI）。研究結果：經過傾向評分配對後，共納入209,568名患者進行分析（每組各104,784人）。在接種疫苗後的第一年內，疫苗組進展至ESRD的風險顯著低於未接種組（HR 0.80; 95% CI 0.74–0.86），其接受透析（HR 0.69; 95% CI 0.62–0.76）與腎臟移植（HR 0.41; 95% CI 0.33–0.52）的風險亦大幅降低。儘管長期追蹤顯示ESRD複合結局的保護效應隨著時間推移而逐漸減弱，但疫苗組對於透析起始的保護效益仍可持續長達五年（整個追蹤期間整體HR 0.92; 95% CI 0.87–0.96）。次族群分析結果進一步指出，帶狀皰疹疫苗的腎臟保護效益在年齡介於50至64歲、女性、亞洲族裔、CKD早期患者以及接種重組次單位疫苗（Shingrix）的族群中尤為顯著。結論：慢性腎臟病患者接種帶狀皰疹疫苗（特別是重組次單位疫苗 Shingrix），與其短期內顯著降低不良腎臟結局、延緩末期腎臟病（ESRD）進展密切相關，且此保護效果在相對年輕（50–64 歲）之 CKD 患者中更為突出。惟此保護效益具時效性，隨免疫反應衰退而逐步減弱，提示疫苗接種主要延緩而非永久阻止 ESRD 之進展。本研究結果支持將帶狀皰疹疫苗接種納入慢性腎臟病之臨床管理指引、強調及早接種之重要性，並指出未來或需評估追加劑（booster）以維持長期保護效益。

Background: Infection-driven inflammation is an under-recognized contributor to chronic kidney disease (CKD) progression. Patients with CKD are at high risk for herpes zoster (HZ), an infection that triggers systemic inflammation and potentially accelerates nephron loss. This study evaluated the association between HZ vaccination and renal outcomes, including the time-course of any protective effect, in a large-scale CKD cohort. Methods：We conducted a retrospective cohort study using the TriNetX U.S. Collaborative Network database, identifying adults aged ≥ 50 years with CKD stages 1–5 or unspecified between 2012 and 2024. Patients with prior end-stage renal disease (ESRD), HZ history, or severe immunocompromise were excluded. Vaccinated individuals (Zostavax or Shingrix) were matched 1:1 to unvaccinated controls using propensity score matching. The primary outcome was ESRD progression (stage 5 CKD, dialysis initiation, or transplantation). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated via Cox regression. Results：The matched analysis included 209,568 patients (104,784 per group). In the first year post-vaccination, the vaccinated cohort showed significantly lower risks of ESRD progression (HR 0.80; 95% CI 0.74–0.86), dialysis initiation (HR 0.69; 95% CI 0.62–0.76), and transplantation (HR 0.41; 95% CI 0.33–0.52). The renoprotective effect against dialysis persisted over five years (overall HR 0.92; 95% CI 0.87–0.96), though differences in composite ESRD attenuated over time. Subgroup analyses revealed enhanced benefits in patients aged 50–64 years, females, Asians, and recipients of the Shingrix vaccine. Conclusion：HZ vaccination—particularly with the recombinant subunit vaccine (Shingrix)—was associated with a significant short-term reduction in adverse renal outcomes and a delay in ESRD progression among patients with CKD, with the most pronounced benefit in relatively younger (aged 50–64 years) patients. However, this protective effect was time-limited and attenuated as vaccine-induced immunity waned, indicating that vaccination delays rather than permanently prevents ESRD progression. These findings support incorporating HZ vaccination into CKD management guidelines and emphasize the value of early vaccination, while suggesting that booster strategies may warrant evaluation to sustain long-term protection.