Serum Versus Urine Free Light Chains for Assessment of Monoclonal Gammopathies

Introduction

Monoclonal gammopathies comprise a spectrum of disorders including Monoclonal Gammopathy of Undetermined Significant (MGUS), Smoldering Multiple Myeloma (SMM), and Active Multiple Myeloma (MM) characterized by production of monoclonal immunoglobulin heavy and/or light chains. Prior to availability of the FREELITE™ (Binding Site Ltd; Birmingham, UK) assay for measurement of immunoglobulin free light chains (FLC), laboratory monitoring of these disorders used predominantly SPEP, quantitation of immunoglobulin heavy chains (quantitative immunoglobulins), and 24 urine collection for total protein and UPEP to extrapolate production of immunoglobulin light chains. The FREELITE™ assay has up to 3-log increased sensitivity (1.5-3.0 mg/L) for detection of free light chains over standard electrophoresis (500-2,000 mg/L) and immunofixation (150-500 mg/L), and since its introduction, has been an integral tool in diagnosis and monitoring of monoclonal gammopathies. This assay detects more plasma cell disorders than SPEP, UPEP and IFE combined due to its higher sensitivity and ability to derive the ratio of affected to unaffected light chain. Measurement of urine FLC using FREELITE™ has not been integrated into standard practice due to presumed variability in FLC concentration due to changes in glomerular filtration, variability in tubular reabsorption of light chains, and lack of data regarding this use. In our practice, we routinely use random urine samples instead of 24 hour urine collections which are cumbersome and suffer from poor patient compliance.

Methods:

The study was approved by the Stratton VA Medical Center Institutional Review Board. As it has been our practice to obtain both random urine along with serum for FLC, we retrospectively reviewed patients diagnosed with monoclonal gammopathies and compared random urine free light chains measured by FREELITE™ to serum FLC and serum quantitative immunoglobulins. Data was analyzed for correlation using Pearson product moment correlation. P values of >0.05 were considered significant.

Results:

We identified 23 individuals, all male (consistent with VA population). Mean (±SD) age was 68±10 years at diagnosis, creatinine 1.3±0.5 mg/dl, and 9±6 pairs of data points per patient. Five (5) had MGUS, 5 SM, and 13 MM (2 light chain only). Results are illustrated in the Table. Normalization of urine results using concurrent serum and urine creatinine did not change the statistical significance of any of the results.

Discussion

While serum FLC is adequate in the majority of patients for monitoring monoclonal gammopathies, urine FLC correlates as well as serum FLC in about ½ of the patients. In addition, in a small number of individuals, urine FLC correlates with serum total serum immunoglobulin better than serum FLC. We feel that random urine FLC is useful for monitoring monoclonal gammopathies, and in a minority of instances, provides more accurate assessment of disease activity than serum.