發(fā)布時間：2018-09-01 05:56

【摘要】：目的： 探討中遠期腎移植受者(術后1年以上)BK病毒感染及其對移植腎功能影響，分析BK病毒感染危險因素。 方法： 選取2013年5月至10月在解放軍第309醫(yī)院隨診的167例中遠期腎移植受者為研究對象，規(guī)律隨訪6個月，每2個月分別留取受者尿液及血液標本，并記錄受者性別、年齡、體重指數(shù)(BMI)、術后時間、免疫抑制方案、供腎類型、手術前后有無糖尿病、是否發(fā)生過移植腎功能延遲恢復(DGF)、是否接受過激素沖擊治療、近期有無其他感染和腎功能情況。應用BKV DNA定量檢測試劑盒和熒光實時定量PCR技術檢測受者尿液和血液中BKV DNA載量，依據(jù)載量結果將研究對象分成四組：病毒血癥組、持續(xù)性病毒尿癥組、一過性病毒尿癥組、陰性對照組。應用SPSS16.0進行統(tǒng)計分析，計量資料采用t檢驗、F檢驗或秩和檢驗，計數(shù)資料采用卡方檢驗或秩和檢驗，比較各組間腎功能情況有無差異，應用logistic回歸法分析遠期腎移植受者BK病毒感染危險因素。 結果： (1)167例受者中病毒血癥組、持續(xù)性病毒尿癥組、一過性病毒尿癥組的發(fā)生率分別為3.6%(6/167)、6.6%(11/167)、8.9%(15/167)。持續(xù)性病毒尿癥陽性率隨著術后時間推移而逐漸降低(1～3年：12.8%；3～5年：4.0%；5～10年：3.1%；≥10年：0%)。持續(xù)性病毒尿癥病毒載量明顯高于病毒血癥(2.0×109vs2.8×106copies/ml，P=0.003)及一過性病毒尿癥(2.0×109vs2.6×106copies/ml，P=0.001)。 (2)病毒血癥隨訪開始時血肌酐值明顯高于持續(xù)性病毒尿癥(203.5±38.6umol/L vs125.8±41.7umol/L，P=0.007)、一過性病毒尿癥(203.5±38.6umol/L vs92.7±26.4umol/L，P=0.000)及陰性對照組(203.5±38.6umol/L vs111.3±59.2umol/L，P=0.000)。病毒血癥血肌酐變化值(隨訪開始時血肌酐值減去出院時血肌酐值)亦明顯高于持續(xù)性病毒尿癥(87.5±25.1umol/L vs40.4±38.1umol/L，P=0.002)、一過性病毒尿癥(87.5±25.1umol/L vs8.3±11.9umol/L，P=0.000)及陰性對照組(87.5±25.1umol/L vs14.0±24.7umol/L，P=0.000)。此外，持續(xù)性病毒尿癥的血肌酐變化值明顯高于一過性病毒尿癥(40.4±38.1umol/L vs8.3±11.9umol/L， P=0.015)及陰性對照組(40.4±38.1umol/L vs14.0±24.7umol/L，P=0.012)。 (3)單因素相關分析示受者年齡、性別、體重指數(shù)、供腎類型、手術前后有無糖尿病、是否使用ATG免疫誘導、是否接受過激素沖擊治療、有無DGF、近期有無其他感染與BK病毒感染無相關性；移植術后時間與BK病毒感染呈負相關(r=-0.174，P=0.025)；相比于CsA，服用FK506為主的免疫抑制方案與BK病毒感染呈正相關(r=0.179,P=0.024)。進一步以CNI類藥物濃度為指標分層，分層分析示FK506濃度(以谷濃度6ng/ml為界)與BK病毒感染無相關性，而CsA濃度(以谷濃度150ng/ml為界)與BK病毒感染呈負相關。以免疫抑制藥物組合方案為指標分層，分層分析示FK506+MZR+Pred或CsA+MMF+Pred與BK病毒感染無相關性，而FK506+MMF+Pred三聯(lián)免疫抑制方案仍與BK病毒感染呈正相關(r=0.186，P=0.030)，CsA+MZR+Pred方案與BK病毒呈負相關(r=-0.177，P=0.016)。多因素分析示移植術后1～2年內受者CNI類免疫抑制藥物谷濃度高(FK5066ng/ml或CsA150ng/ml)是BK病毒感染危險因素(OR=9.375，95%CI=1.035～84.90，，P=0.047)。 結論： 移植術后1～3年內，中遠期腎移植受者BK病毒血癥或持續(xù)性BKV尿癥陽性率高；病毒血癥及持續(xù)性病毒尿癥是導致移植腎功能減退的重要原因；移植術后1～2年內受者藥物谷濃度高(FK5066ng/ml或CsA150ng/ml)是BK病毒發(fā)病危險因素。
[Abstract]:Objective:
Objective To investigate the BK virus infection and its influence on renal function in long-term renal transplant recipients (more than one year after operation) and analyze the risk factors of BK virus infection.
Method:
A total of 167 middle-and long-term renal transplant recipients were selected from May to October 2013 in the 309th Hospital of the PLA. They were followed up regularly for 6 months. Their urine and blood samples were taken every 2 months. Their gender, age, body mass index (BMI), postoperative time, immunosuppressive regimen, donor type, diabetes mellitus before and after operation were recorded. Whether delayed graft function (DGF) has occurred, whether hormone shock therapy has been given, whether there have been other infections and kidney function in the near future. SPSS16.0 was used for statistical analysis. T test, F test or rank sum test were used for quantitative data. Chi-square test or rank sum test were used for quantitative data. Differences in renal function between groups were compared. Logistic regression was used to analyze BK virus infection in long-term renal transplant recipients. Risk factors.
Result:
(1) The incidence of viremia, persistent viruria, transient viruria were 3.6% (6/167), 6.6% (11/167) and 8.9% (15/167), respectively. The positive rate of persistent viruria gradually decreased with the time after surgery (1-3 years: 12.8%; 3-5 years: 4.0%; 5-10 years: 3.1%; 10 years: 0%). Urinary viral load was significantly higher than that of viremia (2.0 x 109 vs 2.8 x 106 copies / ml, P = 0.003) and transient viral urine (2.0 x 109 vs 2.6 x 106 copies / ml, P = 0.001).
(2) The serum creatinine level at the beginning of follow-up was significantly higher in viremia than that in persistent viruria (203.5 6550 The serum creatinine level at the time of discharge was significantly higher than that at the time of discharge in persistent viral urine (87.5 6550 The value of metaplasia was significantly higher than that of transient viruria (40.4
(3) Univariate correlation analysis showed that age, sex, body mass index, type of donor kidney, pre-and post-operative diabetes mellitus, ATG immune induction, hormone shock therapy, DGF and other recent infections were not correlated with BK virus infection, and the time after transplantation was negatively correlated with BK virus infection (r = - 0.174, P = 0.025). Compared with CsA, FK506-based immunosuppressive regimen was positively correlated with BK virus infection (r = 0.179, P = 0.024). Further stratification with CNI concentration as an indicator showed that FK506 concentration (with a threshold of 6ng/ml) was not correlated with BK virus infection, while CsA concentration (with a threshold of 150ng/ml) was negatively correlated with BK virus infection. Hierarchical analysis showed that FK506 + MZR + Pred or CsA + MMF + Pred had no correlation with BK virus infection, while FK506 + MMF + Pred triple immunosuppressive regimen was still positively correlated with BK virus infection (r = 0.186, P = 0.030), and CsA + MZR + Pred regimen was negatively correlated with BK virus infection (r = - 0.177, P = 0.016). The high valley concentration of CNI immunosuppressants (FK5066ng/ml or CsA150ng/ml) in recipients within 1 to 2 years was a risk factor for BK virus infection (OR = 9.375, 95% CI = 1.035-84.90, P = 0.047).
Conclusion:
The positive rate of BK viremia or persistent BKV urine was high in mid-and long-term renal transplant recipients within 1-3 years after transplantation, viremia and persistent viruria were the main causes of renal allograft dysfunction, and the high drug trough concentration (FK5066ng/ml or CsA150ng/ml) in recipients within 1-2 years after transplantation was the risk factor for BK virus.
【學位授予單位】：中國人民解放軍醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R699.2

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