The Serum Free Light Chain Assay Cannot Replace 24-Hour Urine Protein Estimation in Plasma Cell Dyscrasias.

Abstract

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 total10536 (34%)69 (66%)200-499 mg total3120 (65%)11 (35%)≥500 mg total3822 (58%)16 (42%)Total (total ptotein)17478 (45%)96 (55%)<200 mg monoclonal2014 (70%)6 (30%)200-499 mg monoclonal87 (88%)1 (13%)≥500 mg monoclonal1212 (100%)0 (0%)Total (monoclonal protein)4033 (83%)7 (18%)Serum creatinine (mg/dL)Total≤1.01.1–2.02.1–4.0>4.0nAbnormal SFKLR32 (41%)38 (49%)3 (4%)5 (6%)78Normal SFKLR35 (37%)50 (53%)3 (3%)7 (7%)95<200 mg total proteinuria48 (46%)54 (52%)1 (1%)1 (1%)104200–499 mg total proteinuria11 (35%)18 (58%)1 (3%)1 (3%)31>500 mg total proteinuria8 (21%)16 (42%)4 (11%)10 (26%)38