Caglar Kayser, Kinalp Can, Arpaci Fikret, Turan Mustafa, Saglam Kenan, Ozturk Bekir, Komurcu Seref, Yavuz Izzet, Yenicesu Müjdat, Ozet Ahmet, Vural Abdülgaffar
Division of Nephrology, Department of Medicine and. Division of Medical Oncology, Gülhane Medical School, Etlik, Ankara, Turkey.
Nephrol Dial Transplant. 2002 Nov;17(11):1931-5. doi: 10.1093/ndt/17.11.1931.
Nephrotoxicity is one of the most frequent dose-limiting factors of high-dose chemotherapy to create tolerance of autologous peripheral blood stem-cell transplantation (PBSCT) for the treatment of malignant diseases. The relative importance of factors that may be responsible for the development of nephrotoxicity varied in different trials.
The factors affecting nephrotoxicity in the early period of high-dose ifosfamide, carboplatin and etoposide treatment (ICE) followed by autologous PBSCT was investigated in 47 patients. ICE was given as a conditioning regimen for 6 days. Nephrotoxicity was defined as an increase in the serum creatinine concentration of 0.5 mg/dl or more over individual baseline levels.
Eleven patients developed nephrotoxicity (23.4%). There was no significant difference in baseline renal function between patients with nephrotoxicity and those without. No differences were found between the two groups in terms of average total doses of ICE, infections and antibiotic use. The age of patients was higher in those with nephrotoxicity (37+/-3.7 vs 26+/-1.7 years, P=0.019). The cumulative cisplatin dose administered prior to this regimen was higher in the group that developed nephrotoxicity (470 vs 227 mg/m(2), P=0.02). The overall mortality rate was 17%, but the transplant-related deaths were higher in the presence of nephrotoxicity (54.5 vs 5.5%, P=0.001).
The cumulative dose of cisplatin is a strong risk factor for the development of nephrotoxicity in patients who receive high doses of ICE followed by PBSCT. Nephrotoxicity may occur with much lower doses than the currently recommended maximum doses.
肾毒性是高剂量化疗中最常见的剂量限制因素之一，用于使自体外周血干细胞移植（PBSCT）产生耐受性以治疗恶性疾病。在不同试验中，可能导致肾毒性发生的因素的相对重要性各不相同。
对47例接受高剂量异环磷酰胺、卡铂和依托泊苷治疗（ICE）后进行自体PBSCT的患者，研究了早期影响肾毒性的因素。ICE作为预处理方案给药6天。肾毒性定义为血清肌酐浓度较个体基线水平升高0.5mg/dl或更多。
11例患者发生肾毒性（23.4%）。发生肾毒性的患者与未发生肾毒性的患者在基线肾功能方面无显著差异。两组在ICE的平均总剂量、感染和抗生素使用方面未发现差异。发生肾毒性的患者年龄较大（37±3.7岁 vs 26±1.7岁，P = 0.019）。在该方案之前给予的顺铂累积剂量在发生肾毒性的组中更高（470 vs 227mg/m²，P = 0.02）。总死亡率为17%，但在存在肾毒性的情况下移植相关死亡率更高（54.5% vs 5.5%，P = 0.001）。
顺铂累积剂量是接受高剂量ICE后进行PBSCT的患者发生肾毒性的一个强有力的危险因素。肾毒性可能在远低于当前推荐最大剂量的情况下发生。
