The correlation of albumin with total protein concentrations in cerebrospinal fluid across three automated analysers – relevance to the diagnosis of subarachnoid haemorrhage in clinical chemistry practice

Marcus Clarin; Elin Gustafsson; Carina Gustafsson; Maria Lohmander; Henrik Zetterberg

doi:10.1515/cclm-2024-1120

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The correlation of albumin with total protein concentrations in cerebrospinal fluid across three automated analysers – relevance to the diagnosis of subarachnoid haemorrhage in clinical chemistry practice

Marcus Clarin , Elin Gustafsson , Carina Gustafsson , Maria Lohmander and Henrik Zetterberg

Published/Copyright: October 15, 2024

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 4

Keywords: albumin; subarachnoid haemorrhage; method comparison; protein; cerebrospinal fluid

To the Editor,

The guidelines from United Kingdom National External Quality Assessment Services (UK NEQAS) [1] are widely used for the interpretation of absorbance curves of cerebrospinal fluid (CSF) to contribute in the diagnosis of subarachnoid haemorrhage. These guidelines use CSF total protein at a concentration of 1.0 g/L as a variable to detect an impaired function of the blood-brain barrier that could impact the shape of the curve. However, in many laboratories this analysis is not readily available and has been replaced by CSF albumin. Thus, there is a need for a conversion factor between albumin and total protein in CSF.

Using surplus CSF samples (n=45) from routine diagnostics, we analysed the concentrations of albumin and total protein on three instrument platforms: Alinity c (Abbott, Ill, USA), Cobas c701 (Roche Diagnostics, Basel, Switzerland), and Atellica CI (Siemens Healthineers, Erlangen, Germany). CSF total protein and albumin concentrations were measured using reagent kits 07P59 and 08P04 on Alinity (Abbott, Ill, USA), TPUC3 and ALBT2 on Cobas (Roche Diagnostics, Mannheim, Germany), and UCFP and µALB_2 on Atellica (Siemens Healthcare Diagnostics, NY, USA). The use of surplus body fluids such as CSF from routine analysis was approved by the Ethics Committee at the University of Gothenburg (EPN – Gothenburg, Aug 11, 2014). Correlation according to Passing-Bablok between samples was calculated using R (version 4.3.3; http://www.r-project.org/) with package mcr.

Correlations between the analytes are shown in Figure 1. Albumin levels corresponding to a cut-off of total protein of 1.0 g/L are presented in Table 1. The level of 1.0 g/L, as proposed in the guidelines from UK NEQAS is arbitrary [2]. Hence, it is important to always correlate the findings of increased protein content with the clinical presentation.

Figure 1:

Regression analysis (Passing–Bablok) CSF albumin with CSF total protein on Alinity (A), Atellica (B) and Cobas (C). The regression line is indicated in solid blue and the identity line in dashed orange. The shaded blue indicates a 95 % confidence interval. CSF, cerebrospinal fluid.

Table 1:

Levels of albumin corresponding to 1.0 g/L total protein concentration in cerebrospinal fluid.

Instrument platform	Albumin, mg/L	Protein, g/L
Abbott Alinity	632	1.0
Siemens Atellica	526	1.0
Roche Cobas	657	1.0

Using these cut-off levels, it will be possible for a laboratory to analyse albumin instead of total protein in CSF when using the UK NEQAS guidelines. However, further studies are needed to validate the performance of these cut-off levels in a clinical setting.

Corresponding author: Marcus Clarin, MD, Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Enhet 11 Stödfunktioner, 413 45 Göteborg, Mölndal, Sweden; and Department of Laboratory Medicine, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden, E-mail: marcus.clarin@gu.se

Acknowledgments

The authors would like to thank the Univeristy hospital of Region Skåne and the county hospital of Växjö for technical assistance.

Research ethics: The use of surplus body fluids such as CSF from routine analysis was approved by the Ethics Committee at the University of Gothenburg (EPN – Gothenburg, Aug 11, 2014).
Informed consent: Not applicable.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: The authors state no conflict of interest.
Research funding: HZ is a Wallenberg Scholar and a Distinguished Professor at the Swedish Research Council supported by grants from the Swedish Research Council (#2023-00356; #2022-01018 and #2019-02397), the European Union’s Horizon Europe research and innovation programme under grant agreement No 101053962, and Swedish State Support for Clinical Research (#ALFGBG-71320).
Data availability: The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

1. Cruickshank, A, Auld, P, Beetham, R, Burrows, G, Egner, W, Holbrook, I, et al.. Revised national guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage. Ann Clin Biochem 2008;45:238–44. https://doi.org/10.1258/acb.2008.007257.Search in Google Scholar PubMed

2. Cruickshank, AM. Revision of national guidelines for cerebrospinal fluid analysis in suspected subarachnoid haemorrhage. Ann Clin Biochem 2008;45:236–7. https://doi.org/10.1258/acb.2008.007256.Search in Google Scholar PubMed

Received: 2024-09-24

Accepted: 2024-09-25

Published Online: 2024-10-15

Published in Print: 2025-03-26

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

https://doi.org/10.1515/cclm-2024-1120

Keywords for this article

albumin; subarachnoid haemorrhage; method comparison; protein; cerebrospinal fluid

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