Diagnosis: Bence-Jones proteinuria
• Current laboratory procedures use protein electrophoresis and immunofixation electrophoresis (IFE) to identify and characterize urine monoclonal light chains. In addition, the monoclonal light chains may be present in sufficient amounts to allow quantification of an M-spike by protein electrophoresis. Measuring the electrophoretic M-spike is the recommended method of monitoring patients with various monoclonal gammopathies, such as multiple myeloma. Monitoring the urine M-spike is especially useful in patients with light chain multiple myeloma in whom the serum M-spike may be absent or present at very low concentrations, whereas the urine M-spike is present at easily detectable concentrations.
• Urine protein electrophoresis interpretation is challenging because it is often necessary to detect monoclonal immunoglobulins in the presence of significant proteinuria. Proteinuria is defined as greater than 150 mg of urine protein in 24 hours; this is equivalent to a more than 0.1.5 protein/creatinine ratio in a random “spot” urine sample.
• To determine the amount of monoclonal protein produced, it is necessary to analyze an aliquot obtained from a 24 -hour urine collection.
• Urine must be concentrated to identify its relevant protein fractions. The concentration of clinically relevant monoclonal light chains can be low in unfractionated urine. Therefore, urine must be concentrated up to 100-fold to visualize all protein fractions. The optimal concentration of protein in urine for appropriate visualization by electrophoresis is 25 to 50 mg protein/mL. Urine can be concentrated using solvent absorption devices, lyophilization, or protein spin columns.
• Monoclonal light chains can occasionally be seen in serum, even though their serum half-life is only 2 to 6 hours. Possible scenarios are as follows:
• Production of large quantities of monoclonal protein by a light chain myeloma.
• Monoclonal light chains can occasionally exist as homotetramers, which are then too large to be filtered through the glomerular basement membrane.
• A reduced number of nephrons due to underlying renal disease, which reduces the clearance of monoclonal light chains.
• Monoclonal light chains may bind to other serum proteins, which are then too large to be filtered through the glomerular basement membrane, and produce multiple bands by serum protein electrophoresis and IFE.
