来氟米特替换霉酚酸酯抗排异方案对移植肾BK病毒相关性肾病预后的影响

Efficacy of leflunomide in the treatment of BK virus-associated nephropathy in transplant kidney

目的肾移植术后BK病毒相关性肾病(BK virus-associated nephropathy,BKVAN)是影响移植肾预后的重要因素,目前认为其发生与免疫抑制过度有关。文中观察来氟米特替换霉酚酸酯抗排异方案对移植肾BKVAN的治疗效果及影响因素。方法对2007年3月至2013年3月期间南京军区南京总医院收治的15例肾移植术后经病理确诊为BKVAN患者给予停用霉酚酸酯并替换为来氟米特治疗,观察替换后患者的血肌酐变化情况、移植肾丢失率以及来氟米特的药物不良反应;并将患者分为移植肾失功组和未失功组,观察2组患者临床情况及移植肾组化结果的差异,分析导致BKVAN患者移植肾失功的原因。结果替换来氟米特后,6例患者移植肾失功并进入透析;9例患者移植肾功能相对稳定,移植肾丢失率为40%。15例患者替换来氟米特前、后高尿酸血症患者分别为8例和5例,白细胞下降与血小板降低均为2例,替换前谷丙酶无升高,替换后1例升高,但所有项目差异替换前后均无统计学意义。失功与未失功组比较,平均血肌酐明显增高[(1.80±0.53)mg/d L vs(2.74±0.58)mg/d L,P=0.007],移植肾组织B淋巴细胞(206.44±144.96 vs 439.67±267.77,P=0.047)、CD68(588.44±271.80 vs 944.67±259.32,P=0.025)明显升高。结论来氟米特治疗BKVAN具有一定有效性和安全性。血肌酐明显升高的患者预后较差,移植肾组织中B淋巴细胞、CD68明显升高可能提示预后不佳。

Objective BK virus-associated nephropathy（BKVAN） after kidney transplantation is a key factor that influence the prognosis of transplant kidney. To our knowledge, it is believed to be associated with immune suppression. We observed the curative effect and influencing factorsof anti-rejection scheme that Leflunomide was administered instead of Mycophenolate Mofetil（MMF） on transplant kidney BKVAN.. Methods This study included 15 kidney transplant recipients with pathologically confirmed BKVAN in Nanjing General Hospital of Nanjing Military Region form March 2007 to March 2013. Leflunomide was administered instead of Mycophenolate Mofetil （MMF）. Serum creatinine level, renal allograft loss rate and side effects of leflunomide were monitored after medication switch. The patients were divided into two groups, which were renal allograft loss group and renal allograft survival group, for further analyses. The differences between each groups in clinical characteristics as well as histochemical features of the transplanted kidneys were analyzed to determine the cause of renal allograft loss in patients with BKVAN. Results Six patients experienced renal allograft loss after switching to leflunomide arid needed hemodialysis, and 9 patients had stable renal allograft function, renal allograft loss rate was 40.0%. Hyperuricemia occurred in 8 patients in the period before the medication switch and in 5 patients after the switch ; a decrease in blood white cell orplateletcount was found in 2 patients during both periods; an increase in Alanine aminotransferase（ALT） level occurred in one patient after the medication switch. There were no statistically significant differences in any of the above parame- ters before and after the medication switch. Compared to allograft survival group, serum creatinine level [ （ 1.80 ± 0.53 ） mg,/dL vs （2.74 ± 0.58） mg/dL, P = 0. 007 ], the number of B lymphocytes [ （ 206.44 ± 144.96） vs （ 439.67 ± 267.77 ）, P = 0. 047 ] and CD68 [ （588.44 ± 271.80 ） vs （944.67 ± 259.32 ）, P = 0. 025 ] in renal allograft tissue were significantly higherin the allograft loss group. ConclusionLeflunomide is a safe and effective medication for BKVAN. Patients with significantly increased serum creatinine level might have a poorer prognosis. Significantly increased B lymphocytes and CD68 ceils in renal allograft tissue might indicate a poor prognosis.