单次与分次全身照射对干细胞移植患者肾功能损伤及其影响因素分析

Analysis of total body irradiation induced renal damage and its influence factors in patients undergoing hematopoietic cell transplantation

目的:探讨造血干细胞移植前全身单次和分次照射对移植患者肾功能的损伤及其影响因素。方法:回顾性分析2001-2010年我院以全身放射(TBI)为基础方案预处理后73例造血干细胞移植患者的临床资料。根据TBI方案不同,分为单次照射组(A组,8 Gy)、分次照射组(B组,12 Gy分6次照射)。根据血清肌酐水平分别评估肾小球滤过率(eGFR)的基线水平及TBI后1、4、12、18和24个月的eGFR变化,肾功能损伤定义为eGFR较基线水平下降≥30%,采用t检验及Kaplan-meier方法对病例随访资料进行肾存活生存曲线分析,比较两种TBI方式对肾功能的损伤。采用逐步逻辑回归方法分析年龄、TBI剂量率、环孢素以及移植物抗宿主病(GvHD)等因素对肾功能损伤的影响。结果:TBI后1和4个月时A组肾损伤的发生率分别为12.20%和34.15%,B组分别为9.37%和21.88%;且肾损伤程度〔(各观察时间点eGFR-基线水平eGFR)/基线水平eGFR〕A组大于B组,4个月时A组为-0.25±0.20,B组-0.14±0.18,差异有统计学意义,P<0.05。12、18和24个月时A组慢性肾损伤的发生率分别为34.15%、48.78%和48.78%,B组分别为28.13%、43.75%和46.88%,A组肾损伤的发生率高于B组,但两组患者各时间点的肾损伤程度差异无统计学意义,P>0.05。Kaplan-meier肾存活生存曲线显示,两组的肾存活函数均趋于下降,但B组肾存活率高于A组。逐步逻辑回归模型分析显示,干细胞移植后肾功能的损伤与年龄密切相关,而与照射剂量、环孢素应用及GvHD无关。结论:单次及分次全身照射均能够造成造血干细胞移植患者的急、慢性肾损伤,但单次照射的早期肾损伤较为明显,分次照射对肾功能的远期影响更小。年龄与干细胞移植患者的肾损伤密切相关。

OBJECTIVE： To investigate renal damage induced by single dose irradiation and fractionated irradiation method, and analyze influencing factors on renal damage in patients undergoing total body irradiation （TBI） conditioning regimens for hematopoietic cell transplantation （HCT）. METHODS： This retrospective study used data from 73 patients undergoing TBI as part of a conditioning regimen before allogeneic HCT during 2001-2010. TBI was delivered as a single fraction of 8 Gy（group A） or 12 Gy in 6 fractions（group B）. Renal function changes from baseline to following 1,4,12,18 and 24 month（s） after TBI were mainly evaluated by eGFR on the basis of serum creatinine concentration, eGFR greater than or equal to 30% of baseline level was defined as renal damage. Compare renal damage of two groups by student t-test and by Kaplan-meier renal survival curve model. The potential influence of such variables as age, dosage rate, cyclospo- riMe A （CsA） and graft-versus-host disease（GvHD）on renal damage was assessed with Stepwise logistic regression meth- od. RESULTS： At 1 and 4 months after TBI, renal damage was observed in 12.20% and 34.15% of group A, 9.37% and 21.88% of group B. The degree of renal damage, estimated by （eGFR of time point-eGFR of baseline）/eGFR of baseline, was more severe in group A （-0.25±0.20） than that in group B （-0.14±0.18 at 4 months）. The difference was significant （P〈0.05） at 4month. At 12,18 and 24 months, chronic renal damage was 34.15% ,48.78%, 48.78%,respectively, of group A, and 28.13%, 43.75%, 46.88% ,respectively,of group B. Although the incidence rate of renal damage was higher in group A, there was no significant difference of renal damage degree between two groups at each time point（P〈0.05）. Kaplan-meier renal survival curves showed a downtrend in both groups. Whereas, renal survival rate of group B was higher than that of group A. Stepwise logistic regression analysis revealed that age, was closed relat- ed with renal damage, but not dosage, CsA or GvHD. CONCLUSIONS： Single-dose TBI and fractionated TBI would in- duce acute or chronic renal damage in patients undergoing HCT. Single-dose TBI inclines to induce acute renal damage, whereas fractionated TBI has less long-term effect on renal damage. Age is closely related with renal damage in patients with HCT.