Falsely elevated serum vancomycin concentrations in hemodialysis patients

Fluorescence polarization immunoassay (FPIA) is the most widely used clinical vancomycin assay in the United States. Questions exist regarding the accuracy of this polyclonal assay in patients with end-stage renal disease (ESRD). While several studies have reported discrepancies in vancomycin serum concentrations determined by FPIA compared with other vancomycin assays, no study has investigated the accuracy of vancomycin serum concentrations determined by FPIA in patients with ESRD undergoing maintenance hemodialysis. Therefore, we compared the assay performance of FPIA and enzyme multiplied immunoassay technique (EMIT) in six subjects with ESRD receiving high-efficiency hemodialysis. Subjects underwent 6 consecutive weeks of hemodialysis treatment with a cellulose acetate dialyzer (CA210) and received 1 g vancomycin intravenously once weekly during the last hour of dialysis. Vancomycin serum concentrations were determined by both EMIT and FPIA methodologies. From the serum concentration results of both assays, vancomycin dosing recommendations were calculated to achieve a desired steady-state peak concentration of 35 mg/L and trough concentration of 10 mg/L. Overall, vancomycin serum concentrations reported by FPIA were significantly higher than those reported by EMIT. The mean difference between assays in the peak serum concentrations at weeks 1, 4, and 6 was 7.5, 11.5, and 11.2 mg/L, respectively. The mean difference in trough serum concentrations at weeks 1, 4, and 6 was 4.2, 6.2, and 5.2 mg/L, respectively. The FPIA overestimation of the EMIT values (calculated as FPIA-EMIT) varied widely among study subjects with a range of 0.0 mg/L to 27.0 mg/L for peak serum concentrations and 0.0 mg/L to 12.8 mg/L for trough serum concentrations. The mean doses calculated based on FPIA results were significantly lower than the EMIT-derived doses. No significant difference was observed in the calculated dosing intervals. These results demonstrate that FPIA significantly overestimates vancomycin serum concentrations compared with EMIT in patients with ESRD undergoing high-efficiency hemodialysis. The overestimation by FPIA may result in significantly different vancomycin dosing recommendations, leading to underdosing and the potential for therapeutic failures. Due to the unpredictability of the overestimation by FPIA, we were unable to formulate vancomycin dosing guidelines for institutions that use FPIA. Therefore, we recommend that the EMIT vancomycin assay be used in patients with ESRD to ensure appropriate dosing.