Defining New Reference Intervals for Serum Free Light Chains in Individuals with Reduced Kidney Function: Results of the Population- Based on Iceland Screens Treats or Prevents Multiple Myeloma (iStopMM) Study

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.542-542
• Main Authors: Einarsson Long, Thorir, Indridason, Olafur Skuli, Palsson, Runolfur, Rögnvaldsson, Sæmundur, Love, Thorvardur Jon, Thorsteinsdottir, Sigrun, Sverrisdottir, Ingigerdur Solveig, Vidarsson, Brynjar, Onundarson, Pall Torfi, Agnarsson, Bjarni Agnar, Sigurdardottir, Margret, Thorsteinsdottir, Ingunn, Olafsson, Isleifur, Thordardottir, Asdis Rosa, Eythorsson, Elias, Jonsson, Asbjorn, Gislason, Gauti, Olafsson, Andri, Steingrimsdottir, Hlif, Kampanis, Petros, Hultcrantz, Malin, Durie, Brian G.M., Harding, Stephen, Landgren, Ola, Kristinsson, Sigurdur Yngvi
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-153827

Background: In addition to serum protein electrophoresis (SPEP) and serum immunofixation (IFE), measurement of serum free light chains (FLC) has become the hallmark for detection, prognostication, and monitoring of monoclonal gammopathies. However, serum FLC levels are heavily dependent on kidney function due to discrepancy in the rate of kidney clearance of the FLC. As chronic kidney disease (CKD) is common in the general population, it is possible that a large number of individuals have false FLC results. A kidney reference interval (eGFR < 60) has previously been published based on small numers (N=688) for serum FLC ratio (0.37-3.10) instead of the standard reference interval (0.26-1.65), but no kidney reference exists for kappa (3.3-19.4mg/L) or lambda (5.7-26.3mg/L). The aim of this study was to define and improve the reference interval for individuals with various degree of decreased kidney function and assess its effect on prevalence of light chain monoclonal gammopathy of undetermined significance (LC-MGUS) among CKD patients. Methods: A total of 80,759 participants of the Iceland Screens, Treats or Prevents Multiple Myeloma (iStopMM) study were included. Participants were screened by SPEP and IFE as well as by serum FLC assay (Freelite®). Serum creatinine (SCr) value closest to the time of screening was used to calculate (CKD-EPI) eGFR. Participants with M-protein, eGFR >60 mL/min/1.73 m2, missing SCr measurements or more than 1 year from the SCr measurement to the iStopMM screening were excluded. Correlation was assessed graphically and using the Spearman correlation coefficient. A nonparametric bootstrapping method was used to calculate the 95% CI. Partitioning was determined based on the proportion of subgroups (sex, age, eGFR) outside the whole group reference interval (4.1%). However, intervals were not partitioned if subgroups included few participants and/or if deemed more applicable and reasonable for clinical practice. LC-MGUS was defined as FLC ratio outside the reference interval and raised FLC level without evidence of monoclonal heavy chain on SPEP or IFE or end-organ damage attributed to the plasma cell proliferative disorder. Results: Of 75,422 individuals who were screened, 6,503 (12%) participants had eGFR < 60 mL/min/1.73 m2, without evidence of monoclonality on SPEP or IFE and were analysed further. The median (IQR) kappa level was 21.7 (16.6-29.4) mg/L, lambda level 19.0 mg/L (14.8-25.0) and FLC ratio 1.16 (0.97-1.39)