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血液透析对多发性骨髓瘤游离免疫球蛋白轻链的高效清除:体外和体内研究

Efficient removal of immunoglobulin free light chains by hemodialysis for multiple myeloma: in vitro and in vivo studies.

作者信息

Hutchison Colin A, Cockwell Paul, Reid Steven, Chandler Katie, Mead Graham P, Harrison John, Hattersley John, Evans Neil D, Chappell Mike J, Cook Mark, Goehl Hermann, Storr Markus, Bradwell Arthur R

机构信息

Department of Renal medicine, Queen Elizabeth Hospital, QEMC, Birmingham, B15 2TH UK.

出版信息

J Am Soc Nephrol. 2007 Mar;18(3):886-95. doi: 10.1681/ASN.2006080821. Epub 2007 Jan 17.

Abstract

Of patients with newly diagnosed multiple myeloma, approximately 10% have dialysis-dependent acute renal failure, with cast nephropathy, caused by monoclonal free light chains (FLC). Of these, 80 to 90% require long-term renal replacement therapy. Early treatment by plasma exchange reduces serum FLC concentrations, but randomized, controlled trials have shown no evidence of renal recovery. This outcome can be explained by the low efficiency of the procedure. A model of FLC production, distribution, and metabolism in patients with myeloma indicated that plasma exchange might remove only 25% of the total amount during a 3-wk period. For increasing FLC removal, extended hemodialysis with a protein-leaking dialyzer was used. In vitro studies indicated that the Gambro HCO 1100 dialyzer was the most efficient of seven tested. Model calculations suggested that it might remove 90% of FLC during 3 wk. This dialyzer then was evaluated in eight patients with myeloma and renal failure. Serum FLC reduced by 35 to 70% within 2 hr, but reduction rates slowed as extravascular re-equilibration occurred. FLC concentrations rebounded on successive days unless chemotherapy was effective. Five additional patients with acute renal failure that was caused by cast nephropathy then were treated aggressively, and three became dialysis independent. A total of 1.7 kg of FLC was removed from one patient during 6 wk. Extended hemodialysis with the Gambro HCO 1100 dialyzer allowed continuous, safe removal of FLC in large amounts. Proof of clinical value now will require larger studies.

摘要

新诊断的多发性骨髓瘤患者中,约10% 因单克隆游离轻链(FLC)导致的管型肾病而出现依赖透析的急性肾衰竭。其中,80%至90%需要长期肾脏替代治疗。血浆置换早期治疗可降低血清FLC浓度,但随机对照试验未显示肾脏恢复的证据。这一结果可通过该治疗方法的低效来解释。骨髓瘤患者FLC产生、分布和代谢的模型表明,血浆置换在3周内可能仅清除总量的25%。为增加FLC清除量,使用了带蛋白渗漏的透析器进行延长血液透析。体外研究表明,Gambro HCO 1100透析器在七种测试透析器中效率最高。模型计算表明,它可能在3周内清除90%的FLC。然后对8例骨髓瘤合并肾衰竭患者使用了这种透析器进行评估。血清FLC在2小时内降低了35%至70%,但随着血管外再平衡的发生,降低速率减缓。除非化疗有效,FLC浓度在随后几天会反弹。另外5例因管型肾病导致急性肾衰竭的患者随后接受了积极治疗,其中3例不再依赖透析。在6周内,一名患者共清除了1.7千克FLC。使用Gambro HCO 1100透析器进行延长血液透析能够持续、安全地大量清除FLC。现在需要更大规模的研究来证明其临床价值。

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