Al-Aly Ziyad, Sachdeva Ashutosh, Philoctete Ashley Jennifer M, Bastani Bahar
Division of Nephrology, Saint Louis University School of Medicine, St Louis, MO 63110, USA.
Nephrology (Carlton). 2006 Apr;11(2):151-5. doi: 10.1111/j.1440-1797.2006.00548.x.
Cyclosporine (CyA) has positively impacted on the outcome of cardiac transplantation; however, the nephrotoxicity associated with CyA has been a major drawback.
In an effort to reduce exposure to CyA and possibly alleviate its nephrotoxic effects, we undertook a therapeutic strategy to switch cardiac transplant patients with biopsy-proven CyA nephrotoxicity from azathioprine (AZA) to mycophenolate mofetil (MMF) with subsequent CyA dose reduction or elimination.
MMF was substituted for AZA in five cardiac transplant patients (four males; mean age, 60 +/- 6 years old; average time from transplant was 7 +/- 3 years) who had biopsy proven evidence of CyA nephrotoxicity, and in whom CyA dose was reduced (3/5) or discontinued (2/5). At the time of the therapeutic intervention, four patients had an average serum creatinine of 230 +/- 62 micromol/L and one patient had just been started on haemodialysis (HD). During an average follow-up period of 42 months, the slope of the inverse serum creatinine significantly improved in three patients and continued to deteriorate in one patient. The patient on HD could be transiently taken off HD. However, he developed a severe episode of cardiac rejection requiring antirejection therapy and increase in the dose of CyA. The patient was subsequently returned back on HD.
In this preliminary report, we show that AZA to MMF switch with subsequent CyA dose reduction or discontinuation may slow down the progression of kidney disease in some patients. However, the patients should be followed closely for evidence of cardiac rejection.
环孢素(CyA)对心脏移植的结果产生了积极影响;然而,与CyA相关的肾毒性一直是一个主要缺点。
为了减少CyA的暴露并可能减轻其肾毒性作用,我们采取了一种治疗策略,将经活检证实有CyA肾毒性的心脏移植患者从硫唑嘌呤(AZA)转换为霉酚酸酯(MMF),随后降低或停用CyA剂量。
在五名心脏移植患者(四名男性;平均年龄60±6岁;移植后平均时间为7±3年)中,用MMF替代了AZA,这些患者经活检证实有CyA肾毒性,且CyA剂量降低(3/5)或停用(2/5)。在进行治疗干预时,四名患者的平均血清肌酐为230±62微摩尔/升,一名患者刚刚开始进行血液透析(HD)。在平均42个月的随访期内,三名患者的血清肌酐倒数斜率显著改善,一名患者继续恶化。进行HD的患者可以暂时停止HD。然而,他发生了严重的心脏排斥反应,需要进行抗排斥治疗并增加CyA剂量。该患者随后又重新开始进行HD。
在这份初步报告中,我们表明从AZA转换为MMF并随后降低或停用CyA剂量可能会减缓一些患者肾脏疾病的进展。然而,应密切随访患者是否有心脏排斥反应的证据。