Matias P, Araujo M R, Romão J E, Abensur H, Noronha I L
Department of Nephrology, Beneficência Portuguesa Hospital, São Paulo, Brazil.
Transplant Proc. 2008 Dec;40(10):3601-5. doi: 10.1016/j.transproceed.2008.07.138.
Reports on the use of sirolimus (SRL) in pancreas transplantation are still limited. The aim of this study was to evaluate the outcome of SRL conversion in pancreas transplant patients. Among 247 patients undergoing simultaneous kidney-pancreas or solitary pancreas transplantation, 33 (13%) were converted to SRL. The reasons for conversion were calcineurin inhibitors (CNI) nephrotoxicity (n = 24; 73%), severe neurotoxicity owing to CNI (n = 1; 3%), severe and/or recurrent acute rejection episodes (n = 7; 21%), gastrointestinal (GI) side effects of mycophenolate mofetil (MMF; n = 5; 15%), and hyperglycemia (n = 4; 12%). Before conversion, all patients were maintained on a CNI, MMF, and low-dose steroids. They were gradually converted to SRL associated with either CNI or MMF withdrawal. Sixty-three percent (n = 15) of patients who were converted owing to CNI nephrotoxicity, showed stable or improved renal function. At 12 months after conversion, serum creatinine levels were significantly decreased in this group (2.2 +/- 0.5 vs 1.6 +/- 0.3 mg/dL; P = .001) and C-peptide values increased (2.9 +/- 1.1.1 vs 3.1 +/- 1.3 nmol/L; P = .018). The only patient with leucoencephalopathy showed improved neurologic status after SRL conversion. All patients converted to SRL because of GI side effects of MMF showed improvements, and none of those converted because of hyperglycemia experienced improvement. There were no episodes of acute rejection after conversion. We concluded that conversion to SRL in pancreas transplantation should be considered an important alternative strategy, particularly for CNI nephrotoxicity and neurotoxicity, and in cases of severe diarrhea due to MMF.
关于西罗莫司（SRL）在胰腺移植中应用的报道仍然有限。本研究的目的是评估胰腺移植患者转换为SRL治疗后的疗效。在247例接受同期肾-胰腺移植或单独胰腺移植的患者中，33例（13%）转换为SRL治疗。转换的原因包括钙调神经磷酸酶抑制剂（CNI）肾毒性（n = 24；73%）、CNI所致严重神经毒性（n = 1；3%）、严重和/或复发性急性排斥反应（n = 7；21%）、霉酚酸酯（MMF）的胃肠道（GI）副作用（n = 5；15%）以及高血糖（n = 4；12%）。转换前，所有患者均接受CNI、MMF和小剂量类固醇治疗。他们逐渐转换为SRL治疗，并停用CNI或MMF。因CNI肾毒性而转换治疗的患者中，63%（n = 15）肾功能稳定或改善。转换治疗后12个月，该组患者的血清肌酐水平显著降低（2.2±0.5 vs 1.6±0.3 mg/dL；P = .001），C肽值升高（2.9±1.1 vs 3.1±1.3 nmol/L；P = .018）。唯一患有白质脑病的患者在转换为SRL治疗后神经状态改善。所有因MMF的GI副作用而转换为SRL治疗的患者均有改善，而因高血糖转换治疗的患者均无改善。转换治疗后无急性排斥反应发生。我们得出结论，胰腺移植中转换为SRL治疗应被视为一种重要的替代策略，特别是对于CNI肾毒性和神经毒性，以及MMF导致的严重腹泻情况。
