Purpose: Retrospective studies have shown that immunoassays measuring free light chains (FLC) in serum are useful for diagnosis and monitoring of multiple myeloma. This study prospectively evaluates the use of FLC assays and, for the first time, investigates the relationship between serum FLC concentrations and the presence and detectability of BenceJones (BJ) proteins in the urine. Patients and Methods: Three hundred seventy-eight paired samples of serum and urine were tested from 82 patients during the course of their disease. The sensitivities of serum FLC analysis and urine immunofixation electrophoresis (IFE) in detecting monoclonal FLC were compared. Serum FLC concentrations required for producing BJ proteins detected by IFE were determined. Results: Abnormal FLC were present in 54% of serum samples compared with 25% by urine tests. In abnormal serum samples for n or E, the sensitivity of IFE to detect the respective BJ proteins in urine were 51% and 35% and the median serum FLC concentrations required to produce detectable BJ proteins were 113 and 278 mg/L. Renal excretions of monoclonal FLC increased with serum concentrations, but excretions significantly decreased at high serum concentrations combined with renal dysfunction. Conclusion: Serum FLC assays are significantly more sensitive for detecting monoclonal FLC than urine IFE analysis. They also have the advantage of FLC quantification and are more reliable for monitoring disease course and response to treatment.

Introduction. mFLC are important markers for the diagnosis and monitoring of MM. This study for the first time determines serum concentrations of mFLC which are required to produce renal overflow and BJP in urine detectable by IFE and evaluates the relationship between urinary excretions of mFLC and renal function. Patients and methods. 378 paired samples of serum and 24-h-urine from 82 patients were evaluated during the course of their disease. Serum FLC concentrations were measured nephelometrically using an automated immunoassay. Urine samples were tested for clonal bands using agarose gel electrophoresis, scanning densitometry and visual checking of electrophoretic gels. BJP were identified by urine IFE. Results. Among the 378 serum samples, 173 (46%) were normal and 205 (54%) were abnormal for FLC k/l ratios, indicating the presence of mFLC, 98 of kappa and 107 of lambda type. In 98 serum samples with mFLC kappa, 48 (49%) were associated with negative urine IFE analysis and 50 (51%) had positive urine tests. The median serum kappa concentrations were 40 mg/L (range 6–710) for negative urines and 113 mg/L (range 7–39500) for positive urines (p=0.001), indicating an almost threefold greater median value which was approximately six times the upper limit of the reference range (3.3.–19.4 mg/L) for samples with positive urine IFE analysis. In 107 serum samples with mFLC lambda, 70 (65%) were negative in urine and 37 (35%) were positive. The median serum concentrations associated with negative urine IFE tests were 44 mg/L (range 3–561) and were 278 mg/L (range 5–7060) for positive urines (p=0.0001), indicating an almost sixfold difference. This was approximately 2.5-fold greater than for kappa, and approximately 11 times the upper limit of the reference range (5.7–26.3 mg/L) for samples with positive urine IFE analysis. Renal excretions of mFLC, in addition, were determined primarily by serum concentrations for lambda, but by serum concentrations, renal function and, probably, molecular changes for kappa. For both, renal excretions significantly decreased at high serum concentrations combined with renal dysfunction. Conclusion. Based on these results, relatively high serum concentrations of mFLC are required to produce renal overflow and positive urine IFE tests for BJP. Furthermore, urine excretions of mFLC are determined primarily by serum concentrations, but also by renal function, particularly for kappa.