Wasan Kishor M, Wong Joyce C, Corr Traci, Pritchard Sheila
Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada, V6T 1Z3.
Cancer Chemother Pharmacol. 2006 Jan;57(1):120-4. doi: 10.1007/s00280-005-0011-x. Epub 2005 Nov 5.
The objective of this study was to determine if total plasma and lipoprotein cholesterol (C) and triglyceride (TG) concentrations could predict the degree of nephrotoxicity caused by the antifungal agent amphotericin B (AmpB); and to use the average amount of potassium supplementation received daily as a indicator of nephrotoxicity in pediatric oncology patients.
Plasma samples from 18 patients (ages < 17 years) who were receiving AmpB due to suspected or confirmed fungal infection at British Columbia Children's Hospital were analyzed for lipid concentrations. The high density lipoprotein (HDL) fractions were separated by precipitation; total (TOT) plasma and fraction C and TG concentrations were measured by enzymatic colorimetric assays; and low density lipoprotein (LDL) C levels were determined by Friedewald's formula. Changes in serum creatinine levels from baseline and amounts of potassium supplementation were used as indicators of nephrotoxicity; both were obtained from patients' medical charts. Pearson correlation coefficients (r) were determined and considered significant if P < 0.05.
The total cumulative AmpB dose, adjusted for weight, does not seem to predict AmpB-induced nephrotoxicity. Positive but relatively weak correlations were found between total potassium supplementation and LDL C (r = 0.489, P < 0.02); and TOT C (r = 0.551, P < 0.01). In addition, a positive but relatively weak correlation between the average amount of potassium supplementation per day above baseline and HDL C (r = 0.407; P < 0.02) was observed.
Differences in total plasma and LDL cholesterol concentrations may be used as predictors of AmpB-induced nephrotoxicity in pediatric oncology patients.
本研究的目的是确定血浆总胆固醇、脂蛋白胆固醇(C)和甘油三酯(TG)浓度是否能够预测抗真菌药物两性霉素B(AmpB)所致肾毒性的程度;并将每日钾补充剂的平均摄入量作为儿科肿瘤患者肾毒性的一个指标。
对英属哥伦比亚儿童医院18例因疑似或确诊真菌感染而接受AmpB治疗的患者(年龄<17岁)的血浆样本进行脂质浓度分析。通过沉淀法分离高密度脂蛋白(HDL)组分;采用酶比色法测定血浆总胆固醇(TOT)、各组分胆固醇及TG浓度;采用Friedewald公式测定低密度脂蛋白(LDL)胆固醇水平。将血清肌酐水平相对于基线的变化以及钾补充剂的摄入量作为肾毒性指标;二者均从患者病历中获取。计算Pearson相关系数(r),若P<0.05,则认为具有显著性。
经体重校正后的AmpB总累积剂量似乎无法预测AmpB所致肾毒性。总钾补充量与LDL胆固醇(r = 0.489,P < 0.02)以及TOT胆固醇(r = 0.551,P < 0.01)之间存在正相关,但相关性相对较弱。此外,观察到高于基线的每日钾补充剂平均摄入量与HDL胆固醇之间存在正相关,但相关性相对较弱(r = 0.407;P < 0.02)。
血浆总胆固醇和LDL胆固醇浓度的差异可作为儿科肿瘤患者AmpB所致肾毒性的预测指标。