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

被引:189
作者
Hutchison, Colin A. [1 ]
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
[1] Queen Elizabeth Hosp, QEMC, Renal Unit, Dept Renal Med, Birmingham B15 2TH, W Midlands, England
[2] Queen Elizabeth Hosp, QEMC, Dept Hematol, Birmingham B15 2TH, W Midlands, England
[3] Binding Site Ltd, Birmingham, W Midlands, England
[4] Univ Birmingham, Sch Med, Div Med Sci, Birmingham, W Midlands, England
[5] Univ Birmingham, Sch Med, Div Immun & Infect, Birmingham, W Midlands, England
[6] Univ Warwick, Sch Engn, Coventry CV4 7AL, W Midlands, England
[7] Gambro Dialysatoren GmbH & Co KG, Hechingen, Germany
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2007年 / 18卷 / 03期
关键词
D O I
10.1681/ASN.2006080821
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:886 / 895
页数:10
相关论文
共 33 条
[21]   The tumor kinetics of multiple myeloma following autologous stem cell transplantation as assessed by measuring serum-free light chains [J].
Pratt, G ;
Mead, GP ;
Godfrey, KR ;
Hu, Y ;
Evans, ND ;
Chappell, MJ ;
Lovell, R ;
Bradwell, AR .
LEUKEMIA & LYMPHOMA, 2006, 47 (01) :21-28
[22]  
Ritz E, 2006, J AM SOC NEPHROL, V17, P911
[23]  
Sanders P W, 1993, Curr Opin Nephrol Hypertens, V2, P246, DOI 10.1097/00041552-199303000-00011
[24]   PATHOBIOLOGY OF CAST NEPHROPATHY FROM HUMAN BENCE-JONES PROTEINS [J].
SANDERS, PW ;
BOOKER, BB .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 89 (02) :630-639
[25]  
SANDERS PW, 1991, LAB INVEST, V64, P527
[26]  
SOLOMON A, 1985, METHOD ENZYMOL, V116, P101
[27]   HUMAN ALPHA-1-MICROGLOBULIN LEVELS IN VARIOUS BODY-FLUIDS [J].
TAKAGI, K ;
KIN, K ;
ITOH, Y ;
ENOMOTO, H ;
KAWAI, T .
JOURNAL OF CLINICAL PATHOLOGY, 1980, 33 (08) :786-791
[28]   Recovery of renal function after autologous stem cell transplantation in myeloma patients with end-stage renal failure [J].
Tauro, S ;
Clark, FJ ;
Duncan, N ;
Lipkin, G ;
Richards, N ;
Mahendra, P .
BONE MARROW TRANSPLANTATION, 2002, 30 (07) :471-473
[29]   PATIENTS WITH MULTIPLE-MYELOMA REQUIRING LONG-TERM DIALYSIS - PRESENTING FEATURES, RESPONSE TO THERAPY, AND OUTCOME IN A SERIES OF 20 CASES [J].
TORRA, R ;
BLADE, J ;
CASES, A ;
LOPEZPEDRET, J ;
MONTSERRAT, E ;
ROZMAN, C ;
REVERT, L .
BRITISH JOURNAL OF HAEMATOLOGY, 1995, 91 (04) :854-859
[30]   Resistance to intercompartmental mass transfer limits β2-microglobulin removal by post-dilution hemodiafiltration [J].
Ward, RA ;
Greene, T ;
Hartmann, B ;
Samtleben, W .
KIDNEY INTERNATIONAL, 2006, 69 (08) :1431-1437