Can serum free light chains replace urine electrophoresis in the detection of monoclonal gammopathies?

We investigated how sensitive serum free light chain (FLC) analysis was for the detection of Bence-Jones protein (BJP) and whether a serum kappa/lambda ratio could replace urine electrophoresis as part of the investigation algorithm for monoclonal gammopathy.

Serum kappa and lambda FLC analysis was performed on 932 consecutive patients investigated for monoclonal gammopathy, along with serum electrophoresis, serum immunofixation where appropriate, and in 483 individuals urine immunofixation. A reference interval for the kappa/lambda ratio was derived from all patients who had normal serum and urine electrophoresis and no B-cell dyscrasia (n = 312).

The 100% reference interval was 0.21-1.44 (median 0.50), lower than that previously published. From the 483 patients who provided urines, BJP was detected in 34, with an abnormal kappa/lambda ratio in 26 of these. Using the reference interval, sensitivity, specificity, negative and positive predictive values of an abnormal kappa/lambda ratio for the presence of BJP were 0.76, 0.96, 0.98 and 0.59 respectively. Seven patients had an abnormal kappa/lambda ratio with no paraprotein.

All kappa/lambda results should be interpreted against a reference interval appropriate for the analyser in use and the population under study. Some urines will be positive for BJP when the serum kappa/lambda ratio is normal, but there is little difference in outcome whether urine for BJP or serum FLC analysis is included in the screening strategy for monoclonal gammopathies. On balance, we believe that it is not yet time to dispense with urine BJP in the investigation of patients with suspected monoclonal gammopathy.