采用移植肾活检评估不同剂量吗替麦考酚酯对移植肾存活的影响  

Effects of different doses of mycophenolate mofetil on renal allograft survival: Evaluation by biopsy

作　　者：季曙明[1] 谢轲楠[1] 陈劲松[1] 文吉秋[1] 程东瑞[1] 李雪[1] 倪雪峰[1] 刘志红[1] 

机构地区：[1]南京军区南京总医院国家肾脏病临床医学研究中心(解放军肾脏病研究所),南京210002

出　　处：《医学研究生学报》2014年第5期491-496,共6页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81270834)

摘　　要：目的 虽然新型强效免疫抑制剂广泛应用,但移植肾的长期存活率并未获得明显提高.文中对肾移植术后使用不同剂量吗替麦考酚酯（MMF）的受者行移植肾活检并从病理和免疫病理方面来评估效果,旨在探讨不同剂量MMF对移植肾长期存活的影响. 方法 选择南京军区南京总医院2008年1月至2009年12月期间,98例首次接受同种异体尸肾移植,并且术后接受他克莫司（FK506） ＋MMF＋糖皮质激素三联免疫抑制方案的受者作为研究对象.根据术后使用MMF的剂量不同分为4组：MMF常规剂量组（MMF用量≥1.5g/d,n=40）,MMF低剂量组（0.5 g/d＜ MMF用量≤1.0g/d,n=27）,MMF超小剂量组（0＜ MMF用量≤0.5 g/d,n=15）和MMF停药组（MMF用量=0,n=6）.观察患者移植肾病理检查、急性排斥反应、慢性排斥反应,移植肾失功的发生情况. 结果 MMF停药组患者停药后3～6个月期间因移植肾慢性排斥反应导致移植肾失功.MMF超小剂量组的急性排斥、慢性排斥和移植肾失功的发生率均明显高于MMF常规剂量组（33.3％ vs 12.5％,46.7％ vs 7.5％,26.6％ vs 2.5％,P＜0.01）.从病理上看,MMF低剂量和MMF超小剂量组慢性间质纤维化、慢性肾小管萎缩、动脉透明样变、局灶节段性肾小球硬化、条索状纤维化、系膜基质增多、球旁纤维化、FK506肾毒性和慢性移植肾肾病的积分和发生率均明显高于MMF常规剂量组.MMF低剂量和MMF超小剂量组移植肾组织细胞浸润（CD4＋,CD8＋,CD68＋,CD138＋细胞）和IL-2R、HLA-DR表达均明显高于MMF常规剂量组.比较MMF低剂量组和MMF常规剂量组移植肾功能稳定的患者移植肾病理学改变,同样发现Banff慢性间质纤维化积分、FK506肾毒性、动脉透明样变、系膜基质、小球旁纤维化、肾小球硬化发生率也存在差异（P＜0.05）.随访3～4年移植肾的存活率,发现MMF低剂量和MMF超小剂量组危险因子分别为1.52和1.78,对移植肾长期存�Objective Despite the extensive application of novel intensified immunosuppressants,the long-term survival rate of renal allografts remains low.This study was to explore the effects of different doses of mycophenolate mofetil （MMF） on long-term survival rate of renal allografts by pathological and immunopathological evaluation of renal biopsies.Methods This study included 98 cases of first cadaveric renal allograft recipients that received FK506 ＋ MMF ＋ glucocorticoid postoperatively.The patients were divided into groups A （routine-dose MMF,≥1.5 g/d,n =40）,B （low-dose MMF,≤1.0g/d,n =27）,C （ultra-low-dose MMF,≤ 0.5 g/d,n =15）,and D （MMF withdrawal,n =6）.Results Renal allograft loss occurred in all the 6 cases of group D at 3-6 months after MMF withdrawal although with continued medication of FK506 and glucocorticoid.Compared with group A,group C showed dramatically increased rates of acute rejection （12.5% vs 33.3%）,chronic rejection （7.5% vs 46.7%）,and allograft loss （2.5% vs 26.6%） （P 〈 0.01）.The incidences of chronic interstitial fibrosis,chronic renal tubular atrophy,arterial hyalinosis,focal segmental glomeruloscerosis,cord-like fibrosis,increased mesangial matrix,juxtaglomerular fibrosis,FK506 nephrotoxicity,and chronic allograft nephropathy were markedly higher in groups B and C than in A,and so were the infiltration of histiocytes （CD4＋,CD8 ＋,CD68 ＋,and CD138 ＋ cells） and expressions of IL-2R and HLA-DR.Three to four years of follow-up showed that both low and ultra-low doses of MMF （risk factor：1.52 and 1.78 respectively） severely affected the long-term survival of the renal allograft.Conclusion In patients with favorable renal function after kidney transplantation,the reduction of MMF to 1.0 g/d can increase the risk of allograft loss and that to 0.5 g/d can be even more dangerous,while the withdrawal of MMF can lead to rapid decrease of renal function or allograft loss,even though the doses of FK506 and steroid remain unchanged.

关 键 词：肾移植 肾活检 吗替麦考酚酯 常规剂量 低剂量 

分 类 号：R699.2[医药卫生—泌尿科学]