Resolving falsely elevated vancomycin levels in KIMS immunoassay due to monoclonal IgM interference

Given its narrow therapeutic index and risk of nephrotoxicity, vancomycin requires accurate concentration monitoring. While immunoassays such as the Kinetic Interaction of Microparticles in Solution (KIMS) are widely used for their speed and simplicity, they are susceptible to interference by paraproteins such as monoclonal immunoglobulins. Here, we present the first case of falsely elevated vancomycin concentrations measured by KIMS due to monoclonal IgM interference, indicated by a 'kinetic flag' error, and evaluated pre-analytical approaches to mitigate this interference. We applied three pre-analytical techniques to overcome this issue: dithiothreitol (DTT) treatment to reduce disulfide bonds in IgM, ultrafiltration with a 100-kDa cutoff to physically remove IgM molecules, and heterophilic blocking tubes (HBT) to neutralize nonspecific binding by heterophilic antibodies. Vancomycin concentrations were measured using both KIMS (Cobas c702, Roche Diagnostics) and Chemiluminescent Microparticle Immunoassay (CMIA, Architect i2000SR, Abbott Laboratories). In pre-vancomycin-dose samples, both DTT treatment and ultrafiltration resolved the 'kinetic flag' error and corrected vancomycin concentrations to below the lower limit of quantification (LLOQ). In post-vancomycin-dose samples, DTT reduced vancomycin concentration to 16.82 μg/mL (93.8% of the naïve concentration), while ultrafiltration reduced it to 9.22 μg/mL (51.4%). HBT treatment did not resolve the error, and falsely elevated results persisted. This study reports the first case of IgM paraprotein interfering with vancomycin measurement by KIMS, underlining the importance of recognizing monoclonal IgM as a potential source of interference. DTT treatment effectively corrected the interference, while ultrafiltration reduced vancomycin concentration, highlighting the need for careful interpretation.