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Pseudohyperphosphatemia in Multiple Myeloma: A Systematic Review of Case Reports and Case Series
Mahsa Dabir1, Maryam Kamrani Mousavi2, Mohana Mohamadi2
1Department of Medical Laboratory Science, School of Paramedical, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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.
Insights
Pseudohyperphosphatemia (PHP) in multiple myeloma (MM) is often a lab artifact from paraproteins, not true hyperphosphatemia. Identifying this interference is key to avoiding misdiagnosis and incorrect treatment for MM patients.
Area of Science:
- Clinical Chemistry
- Hematology
- Oncology
Background:
- Pseudohyperphosphatemia (PHP) is a common laboratory artifact in multiple myeloma (MM).
- It arises from paraprotein interference with colorimetric phosphate assays.
- Misinterpretation can lead to unnecessary investigations and inappropriate patient management.
Purpose of the Study:
- To systematically review and characterize reported cases of PHP in MM patients.
- To identify features distinguishing PHP from true hyperphosphatemia.
- To inform diagnostic and treatment strategies for MM patients with elevated phosphate levels.
Main Methods:
- Comprehensive literature search of PubMed, Scopus, and Web of Science (November 2025).
- Inclusion of English-language case reports and series involving MM patients with hyperphosphatemia.
- Independent data extraction and quality assessment using JBI tools.
Main Results:
- Fourteen studies with 19 patients were included; IgG-kappa paraprotein was most frequent (n=16).
- Elevated phosphate levels in phosphomolybdate assays normalized with protein precipitation, dilutional testing, or alternative methods.
- Only one case of true hyperphosphatemia was confirmed, linked to renal dysfunction.
Conclusions:
- Hyperphosphatemia in MM is frequently due to PHP caused by paraprotein interference.
- Further research is needed to elucidate mechanisms and clinical significance of this interference.
- Accurate differentiation between PHP and true hyperphosphatemia is crucial for optimal MM patient care.
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