|Values are valid only on day of printing.|
Monitoring patients whose urines demonstrate large M-spikes
Confirming the quantitation of specimens that show M-spikes by electrophoresis
Detecting urine monoclonal proteins and identification of specimens that need urine protein electrophoresis
Immunoglobulin light chains are usually cleared from blood through the renal glomeruli and reabsorbed in the proximal tubules so that urine light-chain concentrations are very low or undetectable. The production of large amounts of monoclonal light chains, however, can overwhelm this reabsorption mechanism. The detection of monoclonal light chains in the urine (Bence Jones proteinuria) has been used as a diagnostic marker for multiple myeloma since the report by Dr. H. Bence Jones in 1847.
Current laboratory procedures employ protein electrophoresis and immunofixation for the identification and characterization of urine monoclonal light chains, and the monoclonal light chains may be present in large enough amounts to also be quantitated as an M-spike on protein electrophoresis. The electrophoretic M-spike is the recommended method of monitoring 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 is very small or absent, but the urine M-spike is large.
Just as quantitative serum immunoglobulins by immunonephelometry are a complement to M-spike quantitation by serum electrophoresis, this quantitative urine light-chain assay may be used to complement urine M-spike quantitation by electrophoresis.
KAPPA TOTAL LIGHT CHAIN
LAMBDA TOTAL LIGHT CHAIN
A kappa/lambda (K/L) ratio >6.2 suggests the presence of monoclonal kappa light chains.
A K/L ratio <0.7 suggests the presence of monoclonal lambda light chains.
In 24-hour specimens, a >90% increase in concentration suggests progression or relapse; a >90% decrease suggests treatment response.
Increased kappa and/or lambda light chains may be seen in benign (polyclonal) and neoplastic (monoclonal) disorders.
Unlike the electrophoretic M-spike, this immunoassay quantitates both polyclonal and monoclonal light chains and is therefore not sensitive for detecting small monoclonal abnormalities. A normal kappa/lambda (K/L) ratio does not rule out a monoclonal protein, and an abnormal ratio does not identify a monoclonal protein. Urine protein electrophoresis and immunofixation are more sensitive and specific.
The quantitation of urine kappa light chain by immunonephelometry yields results that are approximately 2 times the values from the electrophoresis M-spike. Sequential results should be compared to previous results obtained by the same methodology.
In a study of 168 urine samples with a monoclonal light chain detected by immunofixation electrophoresis (IFE), there were 20 samples with a normal kappa/lambda (K/L) ratio. These samples had either no M-spike (n=13) or M-spikes <0.5 mg/dL. Conversely, among the 148 cases with an abnormal K/L ratio, there were 12 samples with no M-spike indicating that there is no clear M-spike value at which the K/L ratio identifies monoclonal light chains. In patients with an M-spike, the relationship between the kappa and lambda light-chain quantitation and the size of the M-spike had good correlation (kappa, r=0.94;lambda,r=0.71) and the regression lines had slopes of 2.4 of kappa and 1.1 for lambda.
Interestingly, there was a single case in which the K/L ratio was 24 and the free light-chain K/L ratio was 58, but the IFE showed polyclonal light chains. The patient was post-transplant for a kappa light-chain multiple myeloma and presumably had multiple forms of a monoclonal kappa light chain that migrated in a smear and was a false-negative by IFE.
1. International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003;121:749-757
2. Rajkumar SV, Kyle RA: Multiple myeloma diagnosis and treatment. Mayo Clin Proc 2005;80(10):1371-1382
3. Snyder MR, Clark R, Bryant SC, Katzmann JA: Quantitation of urinary light chains. Clin Chem 2008;54(10):1744-1746