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Background: Quantification of serum free light chains (FLC) is important in the diagnosis of plasma cell diseases where an abnormal kappa:lambda ratio infers a population of monoclonal plasma cells. The Freelite™ and N Latex assays have been validated in populations without kidney disease but there is a paucity of data relating to the use of these assays in end stage kidney disease (ESKD). The aim of the study was to compare FLC assay performance in ESKD patients on haemodialysis., Methods: Cross-sectional multi-centre study comparing the performance of the two assays on 112 haemodialysis patients without known paraproteinaemia. We quantified FLC pre- and post-dialysis using both the N Latex and the Freelite assays., Results: FLC levels were elevated by both assays. Lambda FLC levels were considerably higher by the N Latex assay. Using the proposed renal reference range for Freelite (0.37-3.1) all but one patient had normal kappa:lambda FLC ratios. In contrast, there were no abnormal FLC ratios pre-dialysis using the N Latex assay. This was due to lambda FLC reading significantly higher by the N Latex assay. Kappa and lambda FLC levels decreased with dialysis but remained elevated above the normal range. The excess of lambda FLC by N Latex persisted post-dialysis but was somewhat attenuated. Dialysis adequacy and dialysis modality predicted clearance of kappa and lambda FLC by both assays., Conclusions: The N Latex assay reported significantly higher pre-dialysis lambda FLC concentrations compared with the Freelite assays. Clinicians should be aware of the need for a separate renal reference range for interpreting FLC ratio using the Freelite assay but not for the N Latex assay in ESKD patients.

Background: The purpose of this study was to evaluate a combined κ and λ light chain immunofixation (CLIF) as a screening tool to detect monoclonal immunoglobulins in serum and urine. A secondary aim was to investigate the impact on workflow and reagent utilisation of a systematic implementation of CLIF in addition to routine protein electrophoresis (PE) on all samples., Methods: Light chain antisera (κ and λ) were mixed in a 1:1 ratio and loaded in the same sequence as the PE to create a superimposable image., Results: The CLIF procedure agreed significantly better with standard immunofixation procedures in the serum and urine. In 33 (22%) new patients and in 114 (15%) follow-up patients CLIF detected a band missed by PE in serum. In 34 (4.5%) of previously categorised cases the monoclonal band was below the detection limit of CLIF in serum, but still detectable by conventional immunofixation electrophoresis. In one case (0.7%) a band in a urine specimen was missed by CLIF compared to 70 (49%) missed by PE. After the systematic introduction of CLIF turn-around-times (TATs) and utilisation of laboratory consumables decreased significantly (p<0.001)., Conclusions: A systematic implementation of CLIF led to the detection of monoclonal bands missed by PE with an improvement in TATs and a decrease in cost.

Background: We compared a novel assay for free light chain (FLC) quantitation based on monoclonal antibodies (N-Latex, Siemens, Germany) to the established polyclonal antibody-based assay (Freelite™, The Binding Site, UK) in AL amyloidosis., Methods: Sixty-two diagnostic samples were analysed on a BNII nephelometer, 32 of which also had a post-treatment sample., Results: In the diagnostic samples: for AL of κ type, the median involved FLC (iFLC) was significantly lower by the N-Latex assay (289 vs. 667 mg/L, p=0.0002) whereas for λ AL the values were similar (148 vs. 161 mg/L, p=0.84). Measurable disease, defined as a difference between involved and uninvolved FLC (dFLC) >50 mg/L was present in 82% by the N-Latex assay compared to 89% by the Freelite™ assay. For diagnostic sensitivity, the FLC ratio was normal in 21% (95% CI 12%-33%) and 15% (95% CI 7%-26%) of patients by the N-Latex and Freelite™ assays, respectively. The combination of serum and urine immunofixation electrophoresis with either FLC assay allowed identification of the amyloidogenic clone in 98% producing comparable sensitivity. For the monitoring samples the median reduction in dFLC was 68% for the N-Latex assay and 77% for the Freelite™ assay (p=0.04). This led to some differences in assigning response categories. Partial response as assigned by both assays predicted overall survival (N-Latex p=0.0015, Freelite™ p=0.022)., Conclusions: There are differences between FLC as measured by the N-Latex and Freelite™ assays, but overall the two assays have similar diagnostic sensitivity. Disease response calculated by both assays predicts survival but more clinical validation is required.

Background: Abbott Diagnostics have developed a new highly sensitive troponin I (hs-TnI) assay. We have assessed its analytical characteristics and applied the assay to a population of apparently cardio-healthy persons., Methods: We assessed imprecision, bias compared to the previous generation assay, matrix effects, and interferences and applied the assay to an apparently healthy population, deriving the 99th percentile limit of the distribution of values in reference populations for men and women separately., Results: The dynamic range of the assay was ranged from 0.5-50,000 ng/L (pg/mL). The 10% CV was at a concentration of 3.9 ng/L, and the 20% CV was at a concentration of 1.8 ng/L. The new and current version of the TnI assay were highly correlated [slope: 0.98 (95%CI:0.88-1.07), y-intercept:1.20 (95%CI:-2.35-4.75) r²=0.99]. The 99th percentile limit of the distribution of values in a reference population was different for males and females: for males 14.0 ng/L and for females 11.1 ng/L and at these concentrations the assay CV was 5.0%. TnI was detectable in nearly all patient samples from the healthy reference population (98.6%)., Conclusions: This new hs-TnI assay is able to measure to an order of magnitude lower than the current generation TnI assay from the same manufacturer. With TnI being detectable in nearly all apparently healthy subject samples this suggests that TnI presence does not always indicate cardiomyocyte necrosis.