Efficient Removal of Immunoglobulin Free Light Chains by Hemodialysis for Multiple Myeloma

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.

Principles of Separation

“…The dependence of renal response on light chain levels was only present in patients with cast nephropathy. A recent analysis suggested that superior light chain removal could be achieved using a "high cutoff" hemodialysis membrane, not yet available in the United States (38).…”

“…Researchers recently identified soluble urokinase receptor in the plasma of patients with recurrent FSGS, capable of inducing profound albuminuria when incubated with isolated rat glomeruli (38,39). It may be causative in the proteinuria through a mechanism that includes lipid-dependent activation of the a5b3 integrin (44,45).…”

Pathogenesis and treatment of renal failure in multiple myeloma

“…A small study investigating hemodialysis with a protein-leaking dialyzer indicated that large reductions in the concentration of serum-free light chains could be obtained. 47 The same group also investigated the use of high cutoff hemodialysis in combination with systemic treatments and found that 13 of 18 patients with renal failure became dialysisindependent. 48 Renal recovery was also associated with improved survival (Po0.02).…”

Lymphangiogenesis Is Upregulated in Kidneys of Patients With Multiple Myeloma

“…Therefore, it is crucial to identify MM-related renal diseases as early as possible to initiate adequate treatment. Potential therapeutic strategies for improving renal function are chemotherapy, with or without subsequent autologous stem cell transplantation, and extended dialysis with protein-leaking dialyzers (Hutchison et al, 2007). According to in vitro and in vivo data (Arimura et al, 2006), the application of the pituitary adenylate cyclase-activating polypeptide could be a promising alternative in the future.…”