Comparison between immunoturbidimetry, size-exclusion chromatography, and LC-MS to quantify urinary albumin
Open accessAbstract
Background: The accurate and precise measurement of urinary albumin is critical, since even minor increases are diagnostically sensitive indicators of renal disease, cardiovascular events, and risk for death. To gain insights into potential measurement biases, we systematically compared urine albumin measurements performed by LC-MS, a clinically available immunoturbidimetric assay, and size-exclusion HPLC. Methods: We obtained unused clinical urine samples from 150 patients who were stratified by degrees of albuminuria (<20 mg/L, 20–250 mg/L, >250 mg/L) as determined by the immunoturbidimetric assay used in our clinical laboratory (Roche Hitachi 912). Urine albumin was then remeasured via LC-MS and HPLC (Accumin™) assays. Results: The immunoturbidimetric assay, calibrated using manufacturer-supplied serum-derived calibrators (Diasorin), underestimated albumin compared with LC-MS. After calibration with purified HSA, this immunoturbidimetric assay correlated well with LC-MS. HPLC overestimated albumin compared with both LC-MS and immunoturbidimetry. The current LC-MS and HPLC assays both performed poorly at concentrations <20 mg/L. Conclusions: Efforts are needed to establish gold-standard traceable calibrators for clinical assays. LC-MS is a specific method to quantify albumin in native urine when concentrations exceed 20 mg/L, and therefore could be employed for standardization among assays.
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The most reliable method is the immunoturbidimetric laboratory assay, which has >95% sensitivity and specificity to detect moderately increased albuminuria.
“The most reliable method is the immunoturbidimetric laboratory assay, which should be considered the standard for comparison as it has >95% sensitivity and specificity to detect moderately increased albuminuria (505).”
From Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus (2023) · cites this paper as [505]
The Materials and Methods (IMMUNOASSAY; page unavailable) identify immunoturbidimetry as the laboratory’s routine clinical urine-albumin assay. But the Results (METHOD COMPARISON; page unavailable) report that it underestimated albumin with the supplied calibrators, and the paper gives no >95% diagnostic sensitivity or specificity for detecting moderately increased albuminuria. It does not establish immunoturbidimetry as the most reliable method or the standard for comparison. (LLM, conf=0.88)
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“Positive results obtained with such methodologies must be confirmed by an immunoturbidimetric assay in an accredited laboratory (355).”
- Authors
- Shaikh, A., Seegmiller, J. C., Borland, T. M., Burns, B. E., Ladwig, P. M., Singh, R. J., Kumar, R., Larson, T. S., & Lieske, J. C.
- Affiliations
- Department of Internal Medicine
- Department of Laboratory Medicine and Pathology
- Mayo Clinic (US)
- Corresponding author
- Larson, Timothy S
- Lieske, John C
- Venue
- Clinical Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-09-01
- Volume
- 54
- Issue
- 9
- Pages
- 1504-1510
- ISSN
- 0009-9147 (ISSN-L)
- 1530-8561
- PMC
- PMC3903150
- OpenAlex
- W2154993917
- Semantic Scholar
- f93472d96279ee7b10c61247e0c352306001b067
- Cited by
- 50
- References
- 24
- Citations by year
- 2025: 1 · 2024: 6 · 2023: 3 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 1 · 2017: 1 · 2016: 4 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 3.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R21DK077669, R01DK076829)
- Topics
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Scientific Measurement and Uncertainty Evaluation
- Keywords
- urinary albumin, albuminuria, immunoturbidimetric assay, size-exclusion HPLC, LC-MS quantification, assay comparison, measurement bias, assay calibration, assay standardization
- MeSH terms
- Albumins, Albuminuria, Calibration, Chromatography, Gel, Chromatography, High Pressure Liquid, Humans, Immunoassay, Nephelometry and Turbidimetry, Mass Spectrometry
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