The 2005 myeloma diagnosis and management guidelines from the British Committee for Standards in Haematology (

Br J Haematol
2006
;
132
:
410
–451
) state that “Quantification of serum-free immunoglobulin light chain levels (FLC assay) and κ/λ ratio can be used as an alternative to quantifying urinary light chains." This statement is open to the interpretation that 24-hour urine collection can be given up in patients with myeloma in favor of estimating serum free light chains (SFLC). The extent of proteinuria is a powerful predictor of the development of renal dysfunction in the short- as well as long-term. There is correlation between the degree of proteinuria and the rate of progression of renal failure. Thus, proteinuria is an independent mediator of progressive renal dysfunction and not just evidence of glomerular dysfunction. Proteinuria in myeloma patients consists of not only light chains, but also of albumin and other normal proteins - and the SFLC assay provides no information on non-light chain protein excretion. We studied 174 24-hour urine specimen results from myeloma patients where there was detectable proteinuria and where simultaneous SFLC assay was performed to analyze the relationship between the extent of proteinuria and the serum free kappa:lambda ratio (SFKLR; normal 0.26–1.65). As the table below shows, a substantial proportion of myeloma patients with proteinuria have normal SFKLR ratios. Next we analyzed 40 urine samples where monoclonal protein had been quantified. The table below shows the relationship between detectable monoclonal protein in the urine and SFKLR. The SFLC assay is abnormal in most - but not all - situations where there is quantifiable monoclonal protein being excreted in the urine. Here, the sensitivity of the test is 82.5%.

Next, we analyzed the relationship between serum creatinine levels, extent of total proteinuria and SFKLR in the 173 of the 174 samples (1 urine sample did not have a concomitant creatinine value). As the table below shows, there is no significant relationship between SFKLR and serum creatinine (P=0.93), but a very strong one between the extent of proteinuria and serum creatinine (P<0.0001).

Our data show that (1) normal SFKLR cannot rule out significant total proteinuria, (2) SFKLR is not 100% sensitive in detecting monoclonal proteinuria, and (3) the extent of proteinuria but not SFKLR correlates with renal function. We suggest that the SFLC assay cannot replace 24-hour urine protein estimation from a clinical standpoint. Any recommendation to the contrary runs the risk of suboptimal patient monitoring.

Amount of proteinurianAbnormal SFKLRNormal SFKLR
<200 mg total 105 36 (34%) 69 (66%) 
200-499 mg total 31 20 (65%) 11 (35%) 
≥500 mg total 38 22 (58%) 16 (42%) 
Total (total ptotein) 174 78 (45%) 96 (55%) 
<200 mg monoclonal 20 14 (70%) 6 (30%) 
200-499 mg monoclonal 8 7 (88%) 1 (13%) 
≥500 mg monoclonal 12 12 (100%) 0 (0%) 
Total (monoclonal protein) 40 33 (83%) 7 (18%) 
Amount of proteinurianAbnormal SFKLRNormal SFKLR
<200 mg total 105 36 (34%) 69 (66%) 
200-499 mg total 31 20 (65%) 11 (35%) 
≥500 mg total 38 22 (58%) 16 (42%) 
Total (total ptotein) 174 78 (45%) 96 (55%) 
<200 mg monoclonal 20 14 (70%) 6 (30%) 
200-499 mg monoclonal 8 7 (88%) 1 (13%) 
≥500 mg monoclonal 12 12 (100%) 0 (0%) 
Total (monoclonal protein) 40 33 (83%) 7 (18%) 
View Large
Serum creatinine (mg/dL)Total
≤1.01.1–2.02.1–4.0>4.0n
Abnormal SFKLR 32 (41%) 38 (49%) 3 (4%) 5 (6%) 78 
Normal SFKLR 35 (37%) 50 (53%) 3 (3%) 7 (7%) 95 
<200 mg total proteinuria 48 (46%) 54 (52%) 1 (1%) 1 (1%) 104 
200–499 mg total proteinuria 11 (35%) 18 (58%) 1 (3%) 1 (3%) 31 
>500 mg total proteinuria 8 (21%) 16 (42%) 4 (11%) 10 (26%) 38 
Serum creatinine (mg/dL)Total
≤1.01.1–2.02.1–4.0>4.0n
Abnormal SFKLR 32 (41%) 38 (49%) 3 (4%) 5 (6%) 78 
Normal SFKLR 35 (37%) 50 (53%) 3 (3%) 7 (7%) 95 
<200 mg total proteinuria 48 (46%) 54 (52%) 1 (1%) 1 (1%) 104 
200–499 mg total proteinuria 11 (35%) 18 (58%) 1 (3%) 1 (3%) 31 
>500 mg total proteinuria 8 (21%) 16 (42%) 4 (11%) 10 (26%) 38 
View Large

Topics:
free immunoglobulin light chain, plasma cell disorder, urine protein test, proteinuria, multiple myeloma, monoclonal immunoglobulin, creatinine tests, serum, kidney failure, urine specimens, albumins

Disclosure: No relevant conflicts of interest to declare.

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2006, The American Society of Hematology
2006
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