Falsely Elevated Serum Creatinine Associated With IgM Paraproteinemia

Mase, Hiroyasu; Hamano, Naoto; Mizuhara, Ryoko; Nozaki, Tsukasa; Saso, Takayuki; Wada, Takehiko; Asai, Satoshi; Miyachi, Hayato; Fukagawa, Masafumi

doi:10.1016/j.ekir.2019.11.017

Cited by 5 publications

(7 citation statements)

References 9 publications

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“…This was unexpected as published cases reporting IgM interference in enzymatic creatinine methods suggest that this is usually a positive, rather than a negative, interference. [12][13][14][15][16][17] As far as we are aware, this is the first published case of IgM paraproteinaemia causing falsely decreased enzymatic creatinine results. The Roche, Abbott and Siemens enzymatic creatinine methods are based on similar reactions with two incubation periods.…”

Section: Discussionmentioning

confidence: 72%

“…It is possible that these two factors together led to an undetectable creatinine result. Mase et al 15 -who reported a positive interference from IgM paraproteinaemiareported that a similar exaggerated absorbance response occurred due to a precipitate that formed when adding patient blood to reagent two of their enzymatic creatinine method. The exact mechanism of this inconsistent paraprotein precipitation is difficult to elucidate.…”

Section: Discussionmentioning

confidence: 98%

“…However, other researchers have reported varying susceptibilities of positive interference from IgM paraproteinaemia between different enzymatic creatinine manufacturers. 13,15,16 This suggests that despite similar assay design, subtle differences in the pH, preservatives and/or ionic strengths of the reagents between manufacturers could cause some IgM paraproteins to precipitate in some reagent solutions and not others.…”

Section: Discussionmentioning

confidence: 99%

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Negative interference from immunoglobulin M paraproteinaemia on the Roche enzymatic creatinine method

Flowers

Tuddenham

Leiva³

et al. 2022

Ann Clin Biochem

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Although enzymatic creatinine methods are subject to fewer interferences than traditional Jaffe creatinine methods, every method in clinical chemistry has limitations. We report, for the first time in the literature, a case of an immunoglobulin M (IgM) paraproteinaemia causing an undetectably low creatinine result on the Roche enzymatic assay. This interference did not occur with other enzymatic creatinine methods produced by Abbott and Siemens or the Roche Jaffe, VITROS dry slide and liquid chromatography with tandem mass spectrometry (LC-MS/MS) creatinine methods. IgM interference was confirmed as patient serum precipitated with polyethylene glycol (PEG) and anti-IgM antiserum yielded detectable Roche enzymatic creatinine results comparable to unaffected methods. The patient’s serum formed an obvious precipitate when mixed with reagent one of the Roche enzymatic creatinine method. This is in contrast to a report of positive interference from IgM paraproteinaemia in a different enzymatic creatinine method, which showed that a precipitate formed when mixing blood with reagent two. As each patient’s paraprotein has a unique structure, it is possible that there are variations in the chemical characteristics of IgM paraproteins between patients. This, as well as IgM-class antibodies’ tendency to form multimers and aggregates, can lead to unpredictable assay interferences and precipitation tendencies between different manufacturers of enzymatic creatinine reagents and their incubation steps. This case highlights the importance of continuing to question and investigates results that do not fit the clinical picture, especially as more laboratories switch from primarily using traditional Jaffe creatinine methods to enzymatic creatinine methods.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Negative interference from immunoglobulin M paraproteinaemia on the Roche enzymatic creatinine method

Flowers

Tuddenham

Leiva³

et al. 2022

Ann Clin Biochem

View full text Add to dashboard Cite

show abstract

“…5,6 The enzymatic method is regarded as more of an accurate method for staging chronic kidney disease and less susceptible to interference when compared with the Jaffe method. 7 However, uncertainty remains because both methods have not been performed in the same subjects, and most studies are in healthy humans, and any effect of NAC at higher level of creatinine or in patients with chronic kidney disease is not clearly known.…”

mentioning

confidence: 99%

N-Acetylcysteine Interference With Creatinine Measurement: An In Vitro Analysis

McCudden

Clark

Akbari

et al. 2021

Kidney International Reports

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“…Although positive interference for enzymatic creatinine assays by IgM paraproteins have been recognised for some time, [3][4][5][6] and IgM paraprotein interference of enzymatic creatinine assay is noted in the Beckman Coulter instructions for use as a rare interference, negative interferences have only recently been described. One case of negative interference has been described with two IgM kappa paraproteins on a Mindray BS-360e platform, 7 while another case has been described with IgM kappa paraprotein on a Roche enzymatic creatinine method.…”

Section: Discussionmentioning

confidence: 99%

Artefactually low creatinine by Beckman Coulter enzymatic method due to immunoglobulin M paraprotein interference

Li,

Thompson,

Igot

et al. 2023

Ann Clin Biochem

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An 81-year-old man was admitted to hospital with symptomatic coronavirus disease (COVID-19) infection. He had a background of progressive chronic inflammatory demyelinating polyneuropathy associated with Waldenstrom’s macroglobulinaemia. His plasma creatinine on four separate samples was inconceivably low (all ≤13 μmol/L), as measured by a Beckman Coulter enzymatic assay) after being 72 μmol/L 3 months earlier. On further investigation, his serum immunoglobulin M (IgM) was 15.4 g/L and his plasma creatinine measured by Roche enzymatic and Roche Jaffe methods was 62 μmol/L and 64 μmol/L, respectively. This was consistent with results post dilution studies and polyethylene glycol (PEG) precipitation on the Beckman Coulter assay. There was no evidence of similar interference when reviewing creatinine results from 10 other patients with IgM paraproteinaemia who had been tested in our laboratory. Clinicians and laboratorians are reminded that enzymatic creatinine is not free from interferences. IgM paraprotein negative interference of enzymatic creatinine is rare and specific to a patient’s IgM and assay combination, but should be considered in patients with an unexplained low enzymatic creatinine result. Useful investigations to identify an interference include dilution studies, PEG precipitation and measuring creatinine on an alternative method such as Jaffe, mass spectrometry or an enzymatic method from a different platform.

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Falsely Elevated Serum Creatinine Associated With IgM Paraproteinemia

Cited by 5 publications

References 9 publications

Negative interference from immunoglobulin M paraproteinaemia on the Roche enzymatic creatinine method

Negative interference from immunoglobulin M paraproteinaemia on the Roche enzymatic creatinine method

N-Acetylcysteine Interference With Creatinine Measurement: An In Vitro Analysis

Artefactually low creatinine by Beckman Coulter enzymatic method due to immunoglobulin M paraprotein interference

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