Novel renal replacement strategies for the elimination of serum free light chains in patients with kappa light chain nephropathy

European Journal of Medical Research

O Sezer⁴  H-H Neumayer²  U Heider⁴  C Fleissner⁴  M Kaiser⁴  C Müller³  S Rötzer⁴  H Peters²  M Schneider²  B Hocher¹  C Jakob⁴  S Morgera²  L Kleeberg⁴ 

[1] Center for Cardiovascular Research/Institute of Pharmacology, Charité - Universitätsmedizin Berlin, Germany;Department of Nephrology, Charité - Universitätsmedizin Berlin, Germany;Institute for Laboratory Medicine and Pathobiochemistry, Charité - Universitätsmedizin Berlin, Germany;Department of Hematology and Oncology, Charité - Universitätsmedizin Berlin, Germany

关键词: plasmapheresis;    hemofiltration;    hemodialysis;    acute renal failure;    multiple myeloma;    Serum free light chains;   

Others  :  1094041
DOI  :  10.1186/2047-783X-14-2-47

 received in 2008-11-28, accepted in 2008-12-03,  发布年份 2009

【 摘 要 】

Multiple myeloma (MM) is a malignancy with excessive production of monoclonal proteins. At disease presentation 30% of MM patients have significant renal impairment which may progress to renal failure requiring dialysis. Besides chemotherapy extracorporeal elimination procedures such as plasma exchange have been applied as adjuvant strategies to eliminate free light chains from circulating blood, however the efficacy was poor with older techniques. We report about a highly efficient method to eliminate serum free light chain (sFLC) using a newly designed protein leaking membrane in patients suffering from sFLC induced acute renal failure. The protein leaking membrane (HCO 1100) is characterized by increased pore size facilitating elimination of middle molecules such as sFLC kappa (22.5 kD). The HCO 1100 membrane was applied in a hemodialysis and hemodiafiltration mode and compared to standard procedures (high flux hemodialysis, hemodiafiltration and plasma exchange). Hemodiafiltration with the protein leaking membrane HCO 1100 was superior to all other extracorporeal replacement strategies in eliminating sFLC-kappa from circulating blood. A median blood reduction rate of 40.8% (range 13.9% - 66.4%) was achieved during hemodiafiltration. The corresponding peak clearance rate was 25 ml/min. Importantly, the poorest elimination rate was achieved by plasma exchange followed by standard high flux hemodialysis. Extracorporeal elimination strategies with the protein leaking membrane HCO 1100 may be a promising adjuvant treatment strategy for patients with sFLC nephropathy requiring dialysis. Hemodiafiltration and to lesser extend also hemodialysis with the HCO 1100 hemofilter are able to eliminate substantial amounts of sFLC kappa in MM patients.

【 授权许可】

   
2009 I. Holzapfel Publishers

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【 参考文献 】

• [1]Sezer O, Heider U, Zavrski I, Kühne CA, Hofbauer LC: RANK ligand and osteoprotegerin in myeloma bone disease. Blood 2003, 101:2094-2098.
• [2]Heider U, Fleissner C, Zavrski I, Kaiser M, Hecht M, Jakob C, Sezer O: Bone markers in multiple myeloma. Eur J Cancer 2006, 42:1544-1553.
• [3]Jakob C, Sterz J, Zavrski I, Heider U, Kleeberg L, Fleissner C, Kaiser M, Sezer O: Angiogenesis in Multiple Myeloma. Eur J Cancer 2006, 42:1581-1590.
• [4]Zavrski I, Kleeberg L, Kaiser M, Fleissner C, Heider U, Sterz J, Jakob C, Sezer O: Proteasome as an emerging therapeutic target in cancer. Curr Pharm Design 2007, 13:471-485.
• [5]Sezer O, Vesole D, Singhal S, Richardson P, Stadtmauer E, Jakob C, Boral A, Esseltine DL, Mehta J: Bortezomib-induced tumor lysis syndrome in multiple myeloma. Clin Lymphoma Myeloma 2006, 7:233-235.
• [6]Kaiser M, Zavrski I, Sterz J, Jakob C, Fleissner C, Kloetzel PM, Sezer O, Heider U: The effects of the histone deacetylase inhibitor valproic acid on cell cycle, growth suppression and apoptosis in multiple myeloma. Haematologica 2006, 91:248-251.
• [7]Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, Fonseca R, Rajkumar SV, Offord JR, Larson DR, Plevak ME, Therneau TM, Greipp PR: Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003, 78:21-33.
• [8]Clark AD, Shetty A, Soutar R: Renal failure and multiple myeloma: pathogenesis and treatment of renal failure and management of underlying myeloma. Blood Rev 1999, 13:79-90.
• [9]Huang ZQ, Kirk KA, Connelly KG, Sanders PW: Bence Jones proteins bind to a common peptide segment of Tamm-Horsfall glycoprotein to promote heterotypic aggregation. J Clin Invest 1993, 92:2975-2983.
• [10]Misiani R, Remuzzi G, Bertani T, Licini R, Levoni P, Crippa A, Mecca G: Plasmapheresis in the treatment of acute renal failure in multiple myeloma. Am J Med 1979, 66:684-688.
• [11]Picken MM, Shen S: Immunoglobulin light chains and the kidney: an overview. Ultrastruct Pathol 1994, 18:105-112.
• [12]Sanders PW, Herrera GA: Monoclonal immunoglobulin light chain-related renal diseases. Semin Nephrol 1993, 13:324-341.
• [13]Nowrousian MR, Brandhorst D, Sammet C, Kellert M, Daniels R, Schuett P, Poser M, Mueller S, Ebeling P, Welt A, Bradwell AR, Buttkereit U, Opalka B, Flasshove M, Moritz T, Seeber S: Serum free light chain analysis and urine immunofixation electrophoresis in patients with multiple myeloma. Clin Cancer Res 2005, 11:8706-8714.
• [14]Johnson WJ, Kyle RA, Pineda AA, O'Brien PC, Holley KE: Treatment of renal failure associated with multiple myeloma. Plasmapheresis, hemodialysis, and chemotherapy. Arch Intern Med 1990, 150:863-869.
• [15]Clark WF, Stewart AK, Rock GA, Sternbach M, Sutton DM, Barrett BJ, Heidenheim AP, Garg AX, Churchill DN, Canadian Apheresis Group: Plasma Exchange When Myeloma Presents as Acute Renal Failure. A Randomized, Controlled Trial. Ann Intern Med 2005, 143:777-784.
• [16]Morgera S, Haase M, Kuss T, Vargas-Hein O, Zuckermann-Becker H, Melzer C, Krieg H, Wegner B, Bellomo R, Neumayer HH: Pilot study on the effects of high cutoff hemofiltration on the need for norepinephrine in septic patients with acute renal failure. Crit Care Med 2006, 34:2099-2104.
• [17]Morgera S, Slowinski T, Melzer C, Sobottke V, Vargas-Hein O, Volk T, Zuckermann-Becker H, Wegner B, Muller JM, Baumann G, Kox WJ, Bellomo R, Neumayer HH: Renal replacement therapy with high-cutoff hemofilters: Impact of convection and diffusion on cytokine clearances and protein status. Am J Kidney Dis 2004, 43:444-453.
• [18]Morgera S, Klonower D, Rocktaschel J, Haase M, Priem F, Ziemer S, Wegner B, Göhl H, Neumayer HH: TNF-alpha elimination with high cut-off haemofilters: a feasible clinical modality for septic patients? Nephrol Dial Transplant 2003, 18:1361-1369.
• [19]Morgera S, Rocktaschel J, Haase M, Lehmann C, von Heymann C, Ziemer S, Priem F, Hocher B, Gohl H, Kox WJ, Buder HW, Neumayer HH: Intermittent high permeability hemofiltration in septic patients with acute renal failure. Intensive Care Med 2003, 29:1989-1995.
• [20]Morgera S, Slowinski T, Melzer C, Sobottke V, Vargas-Hein O, Volk T, Zuckermann-Becker H, Wegner B, Muller JM, Baumann G, Kox WJ, Bellomo R, Neumayer HH: Renal replacement therapy with high cut-off hemofilters: Impact of convection and diffusion on cytokine clearances and protein status. Am J Kidney Dis 2004, 43:444-453.
• [21]Lee WC, Uchino S, Fealy N, Baldwin I, Panagiotopoulos S, Goehl H, Morgera S, Neumayer HH, Bellomo R: Super high flux hemodialysis at high dialysate flows: an ex vivo assessment. Int J Artif Organs 2004, 27:24-28.
• [22]Mead GP, Carr-Smith HD, Drayson MT, Morgan GJ, Child JA, Bradwell AR: Serum free light chains for monitoring multiple Myeloma. Br J Haematol 2004, 126:348-354.
• [23]Pratt G, Mead GP, Godfrey KR, Hu Y, Evans ND, Chappell MJ, Lovell R, Bradwell AR: The tumor kinetics of multiple myeloma following autologous stem cell transplantation as assessed by measuring serum-free light chains. Leuk Lymphoma 2006, 47:21-28.
• [24]Takagi K, Kin K, Itoh Y, Enomoto H, Kawai T: Human alpha 1-microglobulin in various body fluids. J Clin Pathol 1980, 33:786-791.
• [25]Cserti C, Haspel R, Stowell C, Dzik W: Light-chain removal by plasmapheresis in myeloma-associated renal failure. Transfusion 2007, 47:511-514.
• [26]Hutchison CA, Cockwell P, Reid S, Chandler K, Mead GP, Harrison J, Hattersley J, Evans ND, Chappell MJ, Cook M, Goehl H, Storr M, Bradwell AR: Efficient Removal of Immunoglobulin Free Light Chains by Hemodialysis for Multiple Myeloma: In Vitro and In Vivo Studies. J Am Soc Nephrol 2007, 18:886-895.