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The pathogenesis and diagnosis of acute kidney injury in multiple myeloma

This article has been updated

Abstract

Renal failure remains a principal cause of morbidity for patients with multiple myeloma. Once reversible factors such as hypercalcemia have been corrected, the most common cause of severe renal failure in these patients is a tubulointerstitial pathology that results from the very high circulating concentrations of monoclonal immunoglobulin free light chains. These endogenous proteins can result in isolated proximal tubule cell cytotoxicity, tubulointerstitial nephritis and cast nephropathy (myeloma kidney). Less frequently, high levels of free light chains can lead to immunoglobulin light chain amyloidosis and light chain deposition disease, although these conditions are usually associated with insidious progression of renal failure rather than acute kidney injury. Unless there is rapid intervention, progressive and irreversible damage occurs, particularly interstitial fibrosis and tubular atrophy. Despite advances in our understanding of the pathogenesis of these processes there has been a gap in translating these achievements into improved patient outcomes. The International Kidney and Monoclonal Gammopathy Research Group was formed to address this need. In this Review, we discuss the mechanisms of disease and diagnostic approaches to patients with acute kidney injury complicating multiple myeloma.

Key Points

  • The tubulointerstitial injury, cast nephropathy, is the most common cause of severe acute kidney injury in patients with multiple myeloma

  • Histology findings of acute tubular necrosis and acute tubulointerstitial nephritis should raise a 'red flag' for potential injury from high levels of free light chains in patients with multiple myeloma

  • Standard assessment of renal histology by light microscopy, immunofluorescence and electron microscopy might require the addition of specialist techniques to detect subtle injuries in patients with a monoclonal protein

  • Serum immunoassays can provide a rapid alternative to urine electrophoresis for the identification of monoclonal free light chains

  • Early diagnosis and intervention remain key to preventing irreversible renal injuries in patients with multiple myeloma

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Figure 1: Mechanisms of FLC-induced acute kidney injury.
Figure 2: Screening algorithm for monoclonal disease in AKI.
Figure 3: Diagnostic approach to a patient with renal disease and a monoclonal protein.
Figure 4: Renal injuries induced by free light chains in patients with acute kidney injury.
Figure 5: Immunofluorescence and electron microscopy evaluation of tubulointerstitial damage associated with circulating monoclonal free light chains.

Change history

  • 18 November 2011

    In the version of this article initially published online, reference 2 was incorrect. The error has been corrected for the print, HTML and PDF versions of the article.

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Acknowledgements

The authors of this manuscript would like to thank the other members of the International Kidney and Monoclonal Gammopathy Research Group for their intellectual support in the review process for this manuscript: J. Bladé, P. Cockwell, M. Cook, M. Drayson, J.-P. Fermand, S. Kastritis, R. Kyle, N. Leung and C. Winearls. P. W. Sanders' research was supported by National Institutes of Health grant R01 DK46199 and P30 DK079337 (George M. O'Brien Kidney and Urological Research Centers Program) and the Office of Research and Development, Medical Research Service, Department of Veterans Affairs.

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C. A. Hutchison, V. Batuman, J. Behrens, F. Bridoux, C. Sirac, A. Dispenzieri, G. A. Herrera and P. W. Sanders researched data to include in the manuscript. All authors contributed equally to discussion of content for the article, writing the manuscript 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. The other authors declare no competing interests.

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PubMed and MEDLINE were searched using the terms “multiple myeloma”, “monoclonal protein”, “free light chain”, “acute kidney injury”, “renal/kidney impairment” and “cast nephropathy”. No language restrictions were placed on the search and all publications from 1970 to 2010 were considered.

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Hutchison, C., Batuman, V., Behrens, J. et al. The pathogenesis and diagnosis of acute kidney injury in multiple myeloma. Nat Rev Nephrol 8, 43–51 (2012). https://doi.org/10.1038/nrneph.2011.168

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