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Efficient Removal of Immunoglobulin Free Light Chains by Hemodialysis for Multiple Myeloma: In Vitro and In Vivo Studies

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

^* Renal Medicine; ^|| Hematology, Queen Elizabeth Hospital, QEMC; The Binding Site Ltd., Birmingham; Divisions of Medical Sciences; ^** Immunity and Infection, Medical School, University of Birmingham, Birmingham; School of Engineering, University of Warwick, Coventry, United Kingdom; and ^¶ Gambro Dialysatoren GmbH & Co. KG, Hechingen, Germany

Address correspondence to: Dr. Colin A. Hutchison, Renal Unit, Queen Elizabeth Hospital, QEMC, Birmingham, B15 2TH UK. Phone: +44-121-472-1311; Fax: +44-121-430-6482; me{at}colinhutchison.com

Received for publication August 3, 2006. Accepted for publication November 30, 2006.

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.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673