Pseudohyperphosphatemia associated with high-dose liposomal amphotericin B therapy

Abstract

Background-Acute increases in serum inorganic phosphorus (Pi) up to 4.75 mmol/l in the absence of hypocalcemia and tissue deposition of calcium phosphate were noted in 3 patients receiving liposomal amphotericin B (L-AMB). We investigated L-AMB as a possible cause of pseudohyperphosphatemia.Methods-Serum samples from the index patient were analyzed for Pi content by our laboratory's primary analyzer (Synchron LX20 ) and by an alternate analyzer (Vitros). Clear and lipemic serum pools, and normal saline, were spiked with L-AMB and analyzed by the LX20 Pi method. Ultrafiltration studies were performed on patient and spiked sera.Results-Increased Pi values were obtained only from the LX20 analyzer. There was a direct linear relationship between the concentration of L-AMB in the spiked samples and the LX20 Pi results, indicating a 0.9 mmol/l Pi increase for every 100 mg/l increase in L-AMB. Ultrafiltration normalized the Pi results.Conclusion-Serum Pi results may be falsely increased in patients receiving L-AMB when measured by the LX20 analyzer. This novel cause of pseudohyperphosphatemia is due to interference of L-AMB with the method and is corrected by ultrafiltration of the specimen. Since the LX20 1 Presented in part at the

Spurious Electrolyte Disorders: A Diagnostic Challenge for Clinicians

“…Furthermore, treatment with high dose of liposomal amphotericin B and sample contamination with recombinant tissue plasminogen activator or heparin have been implicated as causes of spurious hyperphosphatemia [64,65,66]. Liposomal amphotericin B-related pseudohyperphosphatemia is attributed to the interference of the drug in the Synchron LX-20 phosphorous assay.…”

“…Liposomal amphotericin B-related pseudohyperphosphatemia is attributed to the interference of the drug in the Synchron LX-20 phosphorous assay. In such cases, normal values are found after removing the liposomal amphotericin B from the samples by ultrafiltration [65]. Alternatively, a different analyzer should be used for the accurate measurement of phosphate levels.…”

Electrolyte Disorders in Cancer Patients

“…The next chapter in this book deals in significant detail about TLS. Of note, pseudohyperphosphatemia has been reported in patients with paraproteinemias and in patients receiving high dose of liposomal amphotericin B for treatment of severe fungal infections [96,104]. The former appears to be the result of interference between the abnormal proteins and the laboratory assay.…”

Case-Control Study and Case Series of Pseudohyperphosphatemia during Exposure to Liposomal Amphotericin B

“…Two in vitro studies demonstrated a dose-dependent, linear rise in phosphorus measurements when serum was spiked with LAmB. A 0.0072-to 0.0090-mmol/liter increase in phosphorus correlated with a 1-mg/liter increase in LAmB concentration (8,10). No effect was observed using a comparable placebo molecule without active drug, leading the authors to conclude that active drug in the liposomal formulation (LAmB) is involved in the assay interference (10).…”

“…The liposomal formulation of amphotericin B (LAmB; AmBisome) may be preferred over other formulations due to a more favorable side effect profile and enhanced tissue penetration, but it is still associated with hypokalemia, likely attributable to increased tubular permeability to monovalent cations, and hypomagnesemia, for which the mechanism is less certain (1)(2)(3). Although the drug is known to cause hypophosphatemia as well, several reports of hyperphosphatemia and pseudohyperphosphatemia have been published (1,(4)(5)(6)(7)(8)(9).…”