A-142 Impact of Demographic and Clinical Factors on Serum Free Light Chain Measurements in a Multi-Ethnic US Population

Abstract Background The measurement of serum free light chains (FLC), including serum free kappa, serum free lambda, and the calculated FLC ratio (kappa/lambda), is crucial to aid in diagnosing and managing plasma cell disorders. These values can be influenced by renal function, gender, age, and ethnicity, which can in turn affect diagnosis and management. This study aims to evaluate the free light chain measurements in a diverse, multi-ethnic US population and investigate the impact of these demographic and clinical factors on serum free kappa and lambda values. Methods Samples from 231 apparently healthy US subjects (F:M = 100:131, median age 59 years) were screened for paraproteins using serum protein electrophoresis (SPE) and immunofixation. FLC levels were measured with the Optilite® Freelite® Kappa and Lambda Kit (The Binding Site, part of Thermo Fisher Scientific). Renal function was assessed by measuring serum creatinine on the c501 analyzer (Roche). Results Monoclonal protein was detected in 10 samples, which were excluded from the calculations. Kappa levels significantly correlated with eGFR (? = -0.193, p = 0.004). In renally impaired participants (eGFR < 60 mL/min/1.73 m², n = 33), the median kappa concentration (IQR) was 20.16 mg/L (16.87-31.49 mg/L), compared to 16.9 mg/L (14.04-20.65 mg/L) in participants with preserved renal function (eGFR = 60 mL/min/1.73 m², n = 188). Kappa values also showed a significant correlation with gender (OR = 1.082, p = 0.002), with males exhibiting higher values (median: 14.06 mg/L, IQR: 15.53-23.05 mg/L) than females (median: 13.56 mg/L, IQR: 13.56-19.12 mg/L). A significant correlation was also observed between age and kappa values (? = 0.176, p = 0.0087). Participants aged =70 years (n = 45) had median kappa (IQR) values of 18.09 mg/L (16.27-23.26 mg/L), while those aged <70 years (n = 176) had median kappa (IQR) values of 17.26 mg/L (13.89-20.94 mg/L). Race-based logistic regression analysis revealed a significant association between black race and elevated kappa values (OR = 1.05, p = 0.013), with a median value of 18.97 mg/L in black participants (n = 83) compared to 16.64 mg/L in other races (n = 138). No correlation was seen between lambda FLC concentration and age, sex, kidney function, or race. In the population with preserved kidney function, the central 95% reference intervals were 9.56-33.48 mg/L for kappa FLC, 7.65-26.07 mg/L for lambda FLC, and 0.76-1.85 for the FLC ratio (rFLC). The 100% diagnostic interval for rFLC was 0.71-2.24. The central 95% rFLC range in our cohort is comparable to a recent US study that included 44% black individuals, with a range of 0.686-2.10, and in the Icelandic iStopMM cohort, which reported a range of 0.57-1.69 for individuals younger than 70 years and 0.61-1.84 for individuals 70 years and older. Conclusion This study demonstrates that serum kappa FLC levels are significantly influenced by renal function, age, gender, and ethnicity, whereas serum free lambda levels are relatively unaffected by these factors. These findings underscore the necessity of considering these factors when interpreting FLC results to ensure accurate diagnosis and management of plasma cell disorders.