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 analyzer is widely used by the clinical laboratories clinicians and laboratory personnel should recognize this interference in order to avoid unnecessary diagnostic procedures and interventions.

Fig. 1. Changes in the serum concentrations of inorganic phosphorus (Pi), Ca, and creatinine in patient A between day 9 and 24 of liposomal amhotericin B (L-AMB) therapy

Symbols: open circles, LX20 results; solid circles, Vitros results; heavy solid horizontal line shows time interval during which L-AMB administration was discontinued; dashed horizontal lines show reference interval. The LX20 and Vitros results on days 13, 16, 18, 21 are as follows: Pi_LX20 = 3.52, 4.75, 1.81, 3.62 mmol/l; Pi_Vitros = 1.78, 1.65, 1.07 and 1.68 mmol/l. L-AMB dose: 10 mg/kg/day on day 1 through 16; 7.5 mg/kg/day on day 18 through 24.

Fig. 2

The relation between liposomal amphotericin B (L-AMB) concentration and LX20 inorganic phosphorus (Pi) result for clear and lipemic serum pools and a normal saline.