The Relationship Between Serum Free Light Chain Levels and Urine Protein in Patients with IgG or IgA Myeloma.
Authors: Mehta J. , Vickrey E. , Ramadurai D. , Voigt E. , Fitzpatrick C. , Singhal S. 
Published: October 2019

Abstract 1810

Poster Board I-836

The serum free light chain (SFLC) assay is often though to be a replacement for the cumbersome process of 24-hour urine collection for monoclonal protein estimation (http://www.freelite.co.uk/initialinvestigationpro-24.asp; accessed 16 July 2009) despite evidence suggesting that SFLC estimation cannot replace urine protein quantification (Singhal et al. Blood 2007; 109:3611-2). We studied results from patients with IgG or IgA myeloma if all the following criteria were satisfied: concomitant SFLC and 24-hour urine specimens analyzed, no oligoclonal proteins, no diminished free light chain levels (involved or uninvolved). The aim was to study the correlation between SFLC and 24-hour urine total protein (24UTP), 24-hour urine monoclonal protein (24UMP) and urine immunofixation electrophoresis (UIFE). Only concordant abnormal SFLC ratios were considered abnormal (Singhal et al. Blood 2009; 114:38-9). 558 samples in 114 patients were identified. SFLC ratio was abnormal in 242 and normal in 316 (including 2 discordant abnormal). UIFE (available in 540) was negative in 290. The proportion of samples with normal SFLC ratio decreased as 24UTP increased (P<0.001): ≤200 mg - 75% of 243, 200-500 mg 33% of 129, 501-1000 mg - 24% of 54, and >1000 mg - 6% of 32. Similarly, the proportion of samples with normal SFLC ratio declined as 24UMP increased (P=0.001): ≤200 mg (including negative) - 41% of 145, 200-500 mg 4% of 28, 501-1000 mg - 0% of 14, and >1000 mg - 0% of 15. SFLC ratio was normal in 84% of samples with negative UIFE and in 26% of samples with positive UIFE (P<0.0001). Among the 47 samples with abnormal SFLC ratio and negative UIFE, the 24UTP was 47-288 mg (median 112). 24UMP was 35 mg in 1, “faint” in 1, and no restricted bands were seen in ther remaining 45. The table shows the relationship between UPEP, UIFE and SFLC amongst the 540 samples where all 3 tests were available. The presence of any restricted band on UPEP, even if too small to quantify, was considered positive.

n=540 Positive UPEP Negative UPEP Positive UIFE Negative UIFE Positive UIFE 222 28 Negative UIFE 17 273 Abnormal SFLC ratio 172 59 184 47 Normal SFLC ratio 67 242 66 243

If a positive UPEP is considered the “gold standard” evidence of the presence monoclonal light chains in the urine, the sensitivity of UIFE in detecting urine monoclonal protein is 93% and that of an abnormal SFLC ratio is 72%. On the other hand, if a positive UIFE is considered the “gold standard” evidence of monoclonal light chains in the urine, the sensitivity of an abnormal SFLC ratio in detecting urine monoclonal protein is 74%. These data, obtained from a much large number of homogeneous clinical samples, confirm our previous observations (Singhal et al. Blood 2007; 109:3611-2) that an abnormal SFLC ratio cannot consistently predict the presence of either non-specific or monoclonal proteinuria. Fortunately, the proportion of urine samples with large aounts of non-specific or monoclonal proteinuria that is associated with normal SFLC ratios is small. The sensitivity of the SFLC ratio in detecting urine monoclonal protein is less than that of UIFE. The SFLC assay cannot replace 24-hour urine collection in clinical practice without compromising patient care. Whether a less cumbersome technique such as a spot (random) urine protein-creatinine ratio - used in conjunction with the SFLC assay - can avert the need for 24-hour urine collections in myeloma patients remains to be investigated.

Disclosures

No relevant conflicts of interest to declare.