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异基因造血细胞移植(Allo-HCT)后使用膦甲酸治疗与肾功能的长期丧失有关。

Treatment with Foscarnet after Allogeneic Hematopoietic Cell Transplant (Allo-HCT) Is Associated with Long-Term Loss of Renal Function.

作者信息

Foster Gena G, Grant Michael J, Thomas Samantha M, Cameron Blake, Raiff Doug, Corbet Kelly, Loitsch Gavin, Ferreri Christopher, Horwitz Mitchell

机构信息

Department of Medical Oncology, Yale University School of Medicine, New Haven, Connecticut.

Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Durham, North Carolina.

出版信息

Biol Blood Marrow Transplant. 2020 Sep;26(9):1597-1606. doi: 10.1016/j.bbmt.2020.05.007. Epub 2020 May 23.

Abstract

Despite a well-established risk of chronic kidney disease (CKD) after allogeneic hematopoietic cell transplant (allo-HCT), the benefits of using nephrotoxic anti-infective agents to treat serious peritransplant infections often outweigh this risk. While there is no consensus on the optimal management of post-allo-HCT human herpes virus 6 (HHV6) reactivation, the nephrotoxic drug foscarnet is often used, although its long-term impact on renal function has not been established. We retrospectively reviewed 987 adult patients who underwent transplantation between 2002 and 2016, of whom 45.3% (n = 447) were exposed to foscarnet. The most frequent indications for foscarnet treatment were cytomegalovirus (n = 257, 57.5%) and HHV6 (n = 139, 31.1%). In the first 3 months post-transplant, patients exposed versus unexposed had similar rates of acute kidney injury and acute kidney failure (defined as 3 times baseline creatinine or <75% baseline estimated glomerular filtration rate [eGFR], 61.6% versus 58.7%, P = .42 and 28.1% versus 26.6%, P = .64, respectively). There was no difference in the eGFR at 3 months (P = .36), but patients treated with foscarnet had significantly lower median eGFRs (mL/min/1.73 m) at 6 months (69.3, interquartile range [IQR] 51.4 to 92.8 versus 77.4, IQR 57.3 to 99.3; P = .009) and 12 months (67.8, IQR 52.7 to 85.0 versus 80.7, IQR 63.1 to 102.0; P < .001), respectively. There was also a significant difference in the decline in eGFR from baseline to 12 months (median 32.8, IQR 14.6 to 53.2 versus 21.9, IQR 6.4 to 37.4; P < .001), irrespective of the duration of foscarnet treatment. Multivariate analysis revealed that patients treated with foscarnet were more likely to experience a >30% decrease in eGFR from baseline to 12 months compared to those who were not (odds ratio, 2.30; 95% CI, 1.40 to 3.78; P = .001). We conclude that foscarnet use following allo-HCT had a profound impact on long-term renal function independent of other transplant-related factors.

摘要

尽管异基因造血细胞移植(allo-HCT)后存在慢性肾脏病(CKD)的既定风险,但使用肾毒性抗感染药物治疗严重的移植后感染的益处通常超过这种风险。虽然对于allo-HCT后人类疱疹病毒6型(HHV6)再激活的最佳管理尚无共识,但肾毒性药物膦甲酸钠经常被使用,尽管其对肾功能的长期影响尚未明确。我们回顾性分析了2002年至2016年间接受移植的987例成年患者,其中45.3%(n = 447)使用了膦甲酸钠。膦甲酸钠治疗最常见的指征是巨细胞病毒(n = 257,57.5%)和HHV6(n = 139,31.1%)。在移植后的前3个月,使用膦甲酸钠与未使用的患者急性肾损伤和急性肾衰竭的发生率相似(定义为肌酐水平为基线的3倍或估计肾小球滤过率[eGFR]低于基线的75%,分别为61.6%对58.7%,P = 0.42和28.1%对26.6%,P = 0.64)。3个月时的eGFR无差异(P = 0.36),但接受膦甲酸钠治疗的患者在6个月时的eGFR中位数(mL/min/1.73 m²)显著较低(69.3,四分位间距[IQR] 51.4至92.8对77.4,IQR 57.3至99.3;P = 0.009),在12个月时也是如此(67.8,IQR 52.7至85.0对80.7,IQR 63.1至102.0;P < 0.001)。从基线到12个月eGFR的下降也存在显著差异(中位数32.8,IQR 14.6至53.2对21.9,IQR 6.4至37.4;P < 0.001),与膦甲酸钠治疗的持续时间无关。多因素分析显示,与未接受膦甲酸钠治疗的患者相比,接受膦甲酸钠治疗的患者从基线到12个月eGFR下降>30%的可能性更大(优势比,2.30;95%可信区间,1.40至3.78;P = 0.001)。我们得出结论,allo-HCT后使用膦甲酸钠对长期肾功能有深远影响,独立于其他与移植相关的因素。

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