PPubMed21 Mar 2023Cited 7×

Evaluation of methods to eliminate analytical interference in multiple myeloma patients with spurious hyperphosphatemia

Xin Tian, Li Zhao, Jin Ma, Jie Lu, Tian-yi Zhu, Yan Liu, Hong-xun Sun

Abstract

Paraproteins are monoclonal immunoglobulins (Igs) or immunoglobulin fractions present in the blood or urine produced by a clonal population of B-cell lineage cells, most commonly plasma cells. The presence of paraproteins may signify a variety of underlying conditions, ranging from a benign process known as monoclonal gammopathy of unknown significance to plasma cell malignancy, that is, multiple myeloma (MM).1 It has been reported that paraproteins often interfere with biochemical immunoassays and result in inaccurate test results.2,3 In particular, there have been several reports indicating

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High IgG‑kappa paraprotein levels cause spurious hyperphosphatemia, but TCA deproteinization and the Vitros dry‑chemical assay effectively remove this interference.

What’s new

i.Identified that IgG‑kappa paraprotein concentrations >50 g/L cause spurious hyperphosphatemia in the Beckman AU5821 acid/molybdate assay.
ii.Demonstrated that trichloroacetic acid (TCA) deproteinization eliminates paraprotein interference and provides accurate phosphate results.
iii.Showed that the Vitros 5.1 FS dry‑chemical method yields phosphate measurements comparable to TCA-treated samples.
iv.Evaluated dilution strategies (H2O, normal saline, low‑value serum) and defined maximum acceptable dilutions for affected samples.

How they did it

The study measured serum phosphate in 50 multiple myeloma patients using the Beckman AU5821 acid/molybdate assay, then applied TCA deproteinization to remove paraproteins. Results were compared with the Vitros 5.1 FS dry‑chemical method and with dilutions using deionized water, normal saline, and low‑phosphate serum, assessing bias% <10% as acceptable.

What they found

3 of 50 patients (6%) showed phosphate pseudo‑elevation (bias% >10%) on the AU5821 assay.
All three cases were IgG‑kappa paraproteins with concentrations >50 g/L.
Bias% between TCA and Vitros methods for these patients was <10%, indicating agreement.
Maximum acceptable dilutions: patient 22 – up to 8‑fold H2O, 4‑fold NS, 2‑fold serum; patient 45 – up to 16‑fold H2O/NS, 2‑fold serum; patient 40 failed all dilutions.

Caveats

✕The incidence of spurious hyperphosphatemia may be under‑estimated due to limited sample size.
✕Dilution methods did not fully eliminate interference, especially in samples with very high paraprotein levels.
✕Study was conducted at a single institution, limiting generalizability.
✕Correlation between paraprotein type/concentration and interference remains inconclusive.

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