Erroneous determination of hyperphosphatemia ('pseudohyperphosphatemia') in sera of patients that have been treated with liposomal amphotericin B (AmBisome).

BACKGROUND: Hyperphosphatemia is not an expected consequence of dosing with amphotericin B formulations. However, hyperphosphatemia or pseudohyperphosphatemia (erroneously high phosphorous measurements) has been variously reported in a number of recent case studies associated with liposomal amphotericin B (L-AmB, AmBisome®). In some of these cases, hyperphosphatemia was assumed to obtain, and direct treatment or alterations to antifungal therapy were carried out. In other cases, pseudohyperphosphatemia was assumed to obtain.
METHODS: Using two different Beckman-Coulter measurement platforms (Synchron® LX20 with PHOSm or PHS chemistry systems) phosphorus values were obtained in human serum titrated with L-AmB or L-AmB placebo (identical composition to L-AmB, but without the drug molecule present).
RESULTS: We demonstrate an L-AmB specific assay interference with the PHOSm chemistry system resulting in a linear (in amphotericin B) upward shift in phosphorus values (pseudohyperphosphatemia) and owing to an L-AmB specific interference with the mannitol containing assay system. Interference is not seen with L-AmB placebo. The PHS chemistry exhibits a minor interference from L-AmB, and it is in the form of lower assay values. L-AmB spiked sera treated with LipoClear* or subjected to ultrafiltration exhibit correct phosphorous values.
CONCLUSION: We demonstrate L-AmB specific assay interference with the PHOSm chemistry system resulting in pseudohyperphosphatemia and owing to an L-AmB dependent alteration in the kinetic performance of the reagent system. The PHS chemistry system exhibits lesser interference from L-AmB, and it is in the form of lower assay values. Two methods of generating reliable phosphorus data (use of LipoClear or the Microcon-30) are provided.