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Novel approaches for reducing free light chains in patients with myeloma kidney

Abstract

Myeloma kidney is a tubulointerstitial pathology that accounts for approximately 80–90% of severe acute kidney injury in patients with multiple myeloma. Unless there is rapid intervention, progressive irreversible damage from interstitial fibrosis and tubular atrophy occurs. Work over the past decade has demonstrated that an early sustained reduction in serum concentrations of pathogenic monoclonal free light chains (FLCs) leads to improved renal recovery rates. In turn, an early improvement in renal function is associated with improved patient survival. An early reduction in FLC levels should therefore become standard of care, although the optimum mechanisms to achieve this depletion of FLCs remain to be determined. To provide a coordinated, cross-disciplinary approach to research in this disease, the International Kidney and Monoclonal Gammopathy Research Group was formed. In this Review, we address the current state of knowledge in the management of myeloma kidney.

Key Points

  • Recovery of renal function in patients with myeloma kidney requires an early substantial reduction in serum free light chain concentrations

  • Immediate treatment with high-dose dexamethasone is essential in patients with myeloma kidney

  • The proteasome inhibitor bortezomib provides rapid and high rates of myeloma response without the need for dose modification in patients with renal failure

  • The immunomodulatory drugs thalidomide and lenalidomide are both associated with improved outcomes in patients with kidney disease associated with myeloma

  • A role for free light chain removal by high cut-off hemodialysis in patients with myeloma kidney remains to be proved

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Figure 1: Probability of renal recovery following reduction in FLC levels.

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C. A. Hutchison, J. Bladé, P. Cockwell, M. Cook, M. Drayson, J.-P. Fermand, E. Kastritis, N. Leung and C. Winearls researched data to include in the manuscript. C. A. Hutchison, J. Bladé, M. Cook, J.-P. Fermand, E. Kastritis, N. Leung and C. Winearls wrote the article. All authors contributed equally to discussion of content for the article, and reviewing and editing of the manuscript before submission.

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Correspondence to Colin A. Hutchison.

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C. A. Hutchison has received speakers bureau honoraria and grant/research support from Binding Site. M. Cook has received speakers bureau honoraria from Celgene and Janssen. The other authors declare no competing interests.

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Hutchison, C., Bladé, J., Cockwell, P. et al. Novel approaches for reducing free light chains in patients with myeloma kidney. Nat Rev Nephrol 8, 234–243 (2012). https://doi.org/10.1038/nrneph.2012.14

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