儿童肾移植受者移植术后一年内发生急性排斥反应的影响因素及预后分析

Influencing factors and outcomes of acute rejection within one year after pediatric kidney transplantation

目的探讨儿童肾移植受者移植术后一年内发生急性排斥反应(acute rejection,AR)的影响因素及AR发生时间对预后的影响。方法选取2011年1月至2021年10月浙江大学医学院附属第一医院肾脏病中心移植时年龄小于18岁的肾移植受者,在排除6例非排斥反应导致的早期移植肾功能丧失受者后,最终有106例受者纳入本次研究。其中,男63例,女43例;年龄15(12,16)岁;供体来源为亲属供肾26例,尸体供肾80例。根据是否发生移植肾AR及AR发生时间,将其分为一年内发生AR组、一年后发生AR组和未发生AR组。回顾性对比分析3组儿童肾移植供、受者的临床特征、AR发生的影响因素和治疗结果。通过单因素方差分析或Kruskal-Wallis检验比较3组AR发生后一年的肾功能情况;以移植肾功能丧失作为随访终点事件,采用Kaplan-Meier生存曲线分析一年内发生AR和一年后发生AR对移植肾生存率的影响。结果106例儿童肾移植受者的中位随访时间为35个月,有17例(16.0%)儿童受者出现了19次AR事件,另89例受者截至随访终点未发生AR(未发生AR组)。其中一年内发生AR者9例(一年内发生AR组),一年后发生AR者8例(一年后发生AR组)。治疗后,有8例(47.1%)的肾功能完全恢复至基线水平,6例(35.3%)未完全恢复至基线水平,3例(17.6%)发生移植肾功能丧失。单因素分析显示,与未发生AR受者比较,受者性别为女、供者年龄小于8岁及术后早期人类细小病毒B19感染是一年内发生AR的危险因素(P=0.032、0.039、0.047)。Kaplan-Meier生存分析结果显示,供者年龄小于8岁和术后早期人类细小病毒B19感染的肾移植人群一年内发生AR的发生率分别为14.5%(8/55)和30.0%(3/10),显著高于供者年龄大于8岁和未感染人类细小病毒B19人群的2.0%(1/51)和6.3%(6/96),差异均有统计学意义(P=0.012和0.004)。以移植肾功能丧失作为随访终点事件,生存分析结果显示,一年内发生AR组和一年后发生AR组的10年移植肾生存率分别为88.9%和65.6%,均低于未发生AR组的98.9%,且生存曲线组间比较,差异均有统计学意义(χ2=4.286,P=0.038;χ2=7.787,P=0.005);但一年内发生AR组和一年后发生AR组移植肾生存率比较,差异无统计学意义(P=0.689)。单因素方差分析和Kruskal-Wallis检验显示,一年内发生AR组在AR发生后3、6、12个月的肾小球滤过率分别为(76.8±51.6)ml·min^(-1)·1.73 m^(-2)、(80.6±56.6)ml·min^(-1)·1.73 m^(-2)和(85.6±40.2)ml·min^(-1)·1.73 m^(-2)。其中,3个月和6个月的肾小球滤过率低于一年后发生AR组的(125.3±39.2)ml·min^(-1)·1.73 m^(-2)和(124.7±38.2)ml·min^(-1)·1.73 m^(-2),组间比较,差异均有统计学意义(P=0.021和0.039);而3个月、6个月、12个月的肾小球滤过率均低于未发生AR组的(112.2±34.2)ml·min^(-1)·1.73 m^(-2)、(115.3±33.2)ml·min^(-1)·1.73 m^(-2)和(117.4±30.2)ml·min^(-1)·1.73 m^(-2),组间比较,差异均有统计学意义(P=0.019、0.020和0.020)。结论受者为女性、供者年龄小于8岁和术后早期人类细小病毒B19感染可能会增加儿童肾移植术后一年内发生AR的概率。移植术后一年内发生AR可能会影响移植肾的长期生存和肾功能。

Objective To explore the influencing factors of acute rejection(AR)within one year after pediatric kidney transplantation(KT)and the effect of AR onset time on prognosis.Methods From January 2011 to October 2021,a total of 112 patients aged under 18 years at the time of transplantation were selected.After excluding 6 of them with early renal non-function caused by non-rejection,106 cases were examined.There were 63 males and 43 females with the age of 15(12,16)years.The donors were living related(n=26)and deceased(n=80).According to the presence/absence and onset time of AR,they were assigned into three groups of AR within one year,AR after one year and non-AR.The relevant clinical data of donor/recipient,influencing factors of AR and therapeutic outcomes of AR were retrospectively compared.One-way ANOVA or Kruskal-Wallis test was utilized for comparing 1-year renal function after the occurrence of AR among three groups.With graft-function loss as an end-point event of follow-up,the effects of AR within one year and AR after one year on survival rate and function of graft-kidney were analyzed by Kaplan-Meier survival curve.Results The median follow-up period of 106 pediatric KT recipients was 35 months.During follow-ups,19 episodes of AR occurred in 17(16.0%)patients and 89 recipients exhibited no AR episode by the end of follow-up(non-AR group).As for initial AR,9 episodes of AR occurred within one year(AR within one year group)and 8 episodes of AR after one year(AR after one year group).After anti-rejection treatment,8 patients(47.1%)achieved full recovery and 6 patients(35.3%)failed to completely normalize and 3 patients(17.6%)developed graft failure.Univariate analysis indicated that,as compared with non-AR group,female recipients,donors aged under 8 years and early postoperative infection with parvovirus B19 were risk factors of AR within one year(P=0.032,P=0.039,P=0.047).Kaplan-Meier survival analysis revealed that the incidence rates of AR within one year in patients with donors aged under 8 years and early postoperative parvoviral infection were 14.5%(8/55)and 30.0%(3/10)respectively.They were significantly higher than 2.0%(1/51)and 6.3%(6/96)of patients with donors aged above 8 years and those without parvoviral infection(P=0.012,P=0.004).With graft-function loss as an end-point event of follow-up,Kaplan-Meier survival analysis showed that 10-year kidney graft survival rate in AR within one year and AR after one year groups were 88.9%and 65.6%.Both were significantly lower than that in non-AR group(98.9%).And the inter-group differences were statistically significant(χ2=4.286,P=0.038;χ2=7.787,P=0.005).However,no significant difference existed in survival rate between AR within one year and AR after one year groups(P=0.689).One-way ANOVA and Kruskal-Wallis test indicated that estimated glomerular filtration rates at 3/6/12 months after an onset of AR in AR within one year group were(76.8±51.6),(80.6±56.6)and(85.6±40.2)ml·min^(-1)·1.73 m^(-2).The values of 3/6 months were lower than(125.3±39.2)and(124.7±38.2)ml·min^(-1)·1.73 m^(-2) in AR after one year group.And the inter-group differences were statistically significant(P=0.021,P=0.039).The values of 3/6/12 months were lower than(112.2±34.2),(115.3±33.2)and(117.4±30.2)ml·min^(-1)·1.73 m^(-2) in non-AR group.And the inter-group differences were also statistically significant(P=0.019,P=0.020,P=0.020).Conclusions Female recipients,donors aged under 8 years and early postoperative infection with parvovirus B19 may elevate the risks of AR in children within one year of KT.AR within one year affects the survival rate of graft-kidney and renal function.