Research article

Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure

Colin A Hutchison^1,2 , Tim Plant³ , Mark Drayson³ , Paul Cockwell^1,2 , Melpomeni Kountouri¹ , Kolitha Basnayake^1,2 , Stephen Harding⁴ , Arthur R Bradwell³ and Graham Mead^3,4

¹  Department of Nephrology, University Hospital Birmingham, UK

²  Department of Medical Sciences, University of Birmingham, UK

³  Department of Immunology, University of Birmingham, UK

⁴  IDRL, The Binding Site, Birmingham, West Midlands, UK

author email corresponding author email

BMC Nephrology 2008, 9:11doi:10.1186/1471-2369-9-11

Published:	22 September 2008

Abstract

Background

Monoclonal free light chains (FLCs) frequently cause rapidly progressive renal failure in patients with multiple myeloma. Immunoassays which provide quantitative measurement of FLCs in serum, have now been adopted into screening algorithms for multiple myeloma and other lymphoproliferative disorders. The assays indicate monoclonal FLC production by the presence of an abnormal κ to λ FLC ratio (reference range 0.26–1.65). Previous work, however, has demonstrated that in patients with renal failure the FLC ratio can be increased above normal with no other evidence of monoclonal proteins suggesting that in this population the range should be extended (reference range 0.37–3.1). This study evaluated the diagnostic sensitivity and specificity of the immunoassays in patients with severe renal failure.

Methods

Sera from 142 patients with new dialysis-dependent renal failure were assessed by serum protein electrophoresis (SPE), FLC immunoassays and immunofixation electrophoresis. The sensitivity and specificity of the FLC ratio's published reference range was compared with the modified renal reference range for identifying patients with multiple myeloma; by receiver operating characteristic curve analysis.

Results

Forty one patients had a clinical diagnosis of multiple myeloma; all of these patients had abnormal serum FLC ratios. The modified FLC ratio range increased the specificity of the assays (from 93% to 99%), with no loss of sensitivity. Monoclonal FLCs were identified in the urine from 23 of 24 patients assessed.

Conclusion

Measurement of serum FLC concentrations and calculation of the serum κ/λ ratio is a convenient, sensitive and specific method for identifying monoclonal FLC production in patients with multiple myeloma and acute renal failure. Rapid diagnosis in these patients will allow early initiation of disease specific treatment, such as chemotherapy plus or minus therapies for direct removal of FLCs.