Miller C B, Waller E K, Klingemann H G, Dignani M C, Anaissie E J, Cagnoni P J, McSweeney P, Fleck P R, Fruchtman S M, McGuirk J, Chao N J
St Agnes Healthcare, Durham, NC, USA.
Bone Marrow Transplant. 2004 Mar;33(5):543-8. doi: 10.1038/sj.bmt.1704408.
The current study assessed renal function based on medical records in adult hematopoietic stem cell transplant (HSCT) recipients with proven or probable invasive fungal infection (IFI) transplanted between 1995 and 2000. We confirm that amphotericin B deoxycholate (AmB-d) is nephrotoxic in a large percentage of HSCT recipients. Due to nephrotoxicity, defined as serum creatinine (SCr) >2.5 mg/dl or a 100% increase in SCr from baseline, 88% of patients treated with AmB-d were switched to a lipid formulation of amphotericin B (LFAB). In total, 53% of patients initiated on AmB-d were switched within the first week of therapy. Significantly more patients (70.6%) treated with AmB-d experienced a 100% increase in SCr from baseline compared to patients treated with either AmBisome (44.4%) or Abelcet (41.2%). A Cox Proportional Hazards Model revealed that, compared to patients initiated on AmBisome or Abelcet, the risk of nephrotoxicity (RR=1.5 vs AmBisome; RR=1.7 vs Abelcet), dialysis (RR=2.4 vs AmBisome; RR=1.4 vs Abelcet), and death (RR=2.0 vs AmBisome; RR=1.1 vs Abelcet) were all increased for patients initiated on AmB-d. Study results suggest that renal function improves and mortality declines when an LFAB is given to HSCT patients as initial therapy rather than as second-line therapy, the current practice.
本研究基于1995年至2000年间接受造血干细胞移植(HSCT)且确诊或疑似侵袭性真菌感染(IFI)的成年患者的病历评估肾功能。我们证实,在大部分HSCT受者中,去氧胆酸两性霉素B(AmB-d)具有肾毒性。由于肾毒性定义为血清肌酐(SCr)>2.5mg/dl或SCr较基线水平升高100%,接受AmB-d治疗的患者中有88%转而接受两性霉素B脂质体剂型(LFAB)治疗。总体而言,开始接受AmB-d治疗的患者中有53%在治疗的第一周内就转而接受其他治疗。与接受两性霉素B脂质体(44.4%)或两性霉素B脂质复合体(41.2%)治疗的患者相比,接受AmB-d治疗的患者中SCr较基线水平升高100%的比例显著更高(70.6%)。Cox比例风险模型显示,与开始接受两性霉素B脂质体或两性霉素B脂质复合体治疗的患者相比,开始接受AmB-d治疗的患者发生肾毒性(与两性霉素B脂质体相比RR=1.5;与两性霉素B脂质复合体相比RR=1.7)、透析(与两性霉素B脂质体相比RR=2.4;与两性霉素B脂质复合体相比RR=1.4)和死亡(与两性霉素B脂质体相比RR=2.0;与两性霉素B脂质复合体相比RR=1.1)的风险均有所增加。研究结果表明,对于HSCT患者,将LFAB作为初始治疗而非当前的二线治疗,可以改善肾功能并降低死亡率。