肾移植患者神经钙蛋白阻滞药的肾毒性

目的:了解减少或停用神经钙蛋白阻滞药能否改善肾移植后慢性移植物肾病患者的肾功能.方法:1999年1月～2001年5月期间,对病理诊断为慢性移植物肾病(Ⅰ级)肾功不全的93例肾移植患者随机分为A、B两组,A组(50例):在1～2周内将其神经钙蛋白阻滞药(环孢素或他克莫司)减少至原剂量的三分之一或完全停用,同时适当增加硫唑嘌呤或霉酚酸脂的用量;B组(43例):环孢素A或他克莫司未作大幅度减量、而是仅适当增加硫唑嘌呤或霉酚酸脂的用量.对两组患者进行至少3年的随访,比较其移植肾功能、观察两组急性排斥反应有无差异等.结果:3年后A组有31例(62.0%)患者移植肾功能得以好转或不再继续恶化,而B组除4例(9.3%)移植肾功能维持在原有水平外,其他患者肾功能均进行性恶化;3年后A组肾功能明显好于B组;B组3年后尿蛋白定量明显增多,而A组无明显改变;两组急性排斥反应发生率无显著差异.结论:大幅度减少甚至停用神经钙蛋白阻滞药可使部分肾移植后慢性移植物肾病患者的肾功能得以改善或者阻止其进行性恶化.这种药物调整是安全的.

Nephrotoxicity Calcineurin Blockers in Renal Transplantation Recipients

Objective: To understand whether reduced or discontinued calcineurin blockers (CNB) has a role improving renal function after transplantation in the renal transplantation recipients with chronic allograft nephropathy (CAN). Method: 93 renal transplantation recipients with declining graft function and CAN proven by biopsy were studied. During 1-2 weeks,50 recipients (group A) were discontinued or reduced to one third of original dosage of CNB ( Cyclosporine or tacrolimus ) and the dosage of azalhioprine (Aza) or mycophenolate mofetil (MMF) was increased of properly. The doses of CNB in other 43 recipients (group B) were not obviously changed but in increasing the dosage of Aza or MMF properly. All patients were followed up three years at least. The renal functions were compared between the two groups. The incidences of acute renal graft rejection were calculated in both groups. Result: Three year later, the patients with stabilized or improved graft functions were 31 cases (62% ) in group A, and 4 cases (9. 3% ) in group B. The difference was significant. During the study period of 3-year, the renal functions in group A was significantly better than that in Group B. The incidences of acute rejection in both groups were not significantly different. Conclusion: For some renal transplantation recipients with declining graft function and CAN proven by biopsy, the drug remarkably reduced or discontinued could stabilize or improve their renal functions. The adjusted doses of immunosuppressants did not increase the risk of acute rejection.