The dilemma: there are a subset of patients with some type of paraproteinemia–e.g., light chain deposition disease or amyloidosis, for instance–which are NEGATIVE by SPEP & UPEP. When there is renal involvement, the diagnosis can potentially be made by renal biopsy. But since we can’t always be as invasive as we’d like to be, don’t forget about the serum free light chain assay.
Measuring serum free light chains relies on an assay which quantitates light chains NOT bound to heavy chain. In this 2003 Am J Clin Pathol study by Abraham et al, serum free light chains was found to be much more sensitive than either serum or urine immunofixation, and was successful in identifying several patients with AL amyloidosis who had undetectable paraproteins by SPEP & UPEP.
Of note, serum light chains are cleared renally–so patients with reduced GFR will have increased values of both kappa and lambda light chain. Thus, for patients with CKD it is essential to look at the kappa:lambda free light chain ratio in order to detect a paraproteinemia.