Pseudohyperphosphatemia in Multiple Myeloma: A Systematic Review of Case Reports and Case Series

BACKGROUND: Pseudohyperphosphatemia (PHP) is a laboratory artifact that may occur in patients with multiple myeloma (MM) due to interference from circulating paraproteins in colorimetric phosphate assays. Misinterpretation of this artifact may lead to unnecessary diagnostic evaluation or inappropriate treatment. This systematic review aims to investigate the reported cases of PHP in patients with MM to describe the features used to distinguish it from true hyperphosphatemia. METHODS: A comprehensive search of PubMed, Scopus, and Web of Science was conducted in November 2025 to identify English-language case reports and series involving MM patients with hyperphosphatemia. Studies were included if they reported hyperphosphatemia or pseudohyperphosphatemia in patients with multiple myeloma. Data extraction and quality assessment were performed independently by two reviewers using JBI tools. RESULTS: Fourteen studies encompassing 19 patients were included. IgG-kappa was the most frequent paraprotein subtype (n = 16). Most patients exhibited elevated phosphate levels via phosphomolybdate-based assays, which normalized with protein precipitation, dilutional testing, or alternative methods such as atomic emission spectroscopy. Only one case of true hyperphosphatemia was confirmed in the setting of renal dysfunction. Several reports described decreases in measured phosphate levels following chemotherapy and reduction of paraprotein concentrations; however, the available data were limited and insufficient to establish a formal correlation. CONCLUSION: Reported cases of hyperphosphatemia in patients with MM are often attributable to PHP caused by paraprotein interference. Further studies are required to better characterize the mechanisms and clinical implications of this laboratory interference.