Liquid chromatography tandem mass spectrometry (LC-MS/MS) candidate reference measurement procedure for urine albumin

Seiei Shiba; Zoi E. Sychev; Michael D. Evans; Jesse C. Seegmiller

doi:10.1515/cclm-2024-1374

Article

Liquid chromatography tandem mass spectrometry (LC-MS/MS) candidate reference measurement procedure for urine albumin

Seiei Shiba , Zoi E. Sychev , Michael D. Evans and Jesse C. Seegmiller

Published/Copyright: April 8, 2025

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 8

Abstract

Objectives

Urine albumin is a key biomarker utilized for diagnosis and monitoring progression of chronic kidney disease (CKD). These characteristics highlight the importance urine albumin serves in patient management. However, laboratory results are confounded by a lack of standardization where results may exceed 40 % difference between diagnostic platforms. This presents serious issues since current guideline clinical decision points are fixed values and misclassification may occur between laboratory methods. Therefore, standardization is needed for urine albumin measurements.

Methods

A liquid chromatography tandem mass spectrometry (LC-MS/MS) reference measurement procedure (RMP) was developed. This RMP employed proteolysis using trypsin and examined six peptides specific to human serum albumin. The National Institute of Standards and Technology 2925 reference material was used to value assign calibrators. To improve imprecision and accuracy, all samples were run in quadruplicate. Urine from 98 patient specimens was analyzed.

Results

RMP final results consisted of averaging four peptide transitions, yielding a 20-day coefficient of variation (CV) of <3.0 %. Factors considered in assigning RMP overall uncertainty included specimen and internal standard pipetting, calibration material, and LC-MS/MS imprecision. This RMP was compared to the Roche Cobas and Siemens Dimension Vista urine albumin assays and was found to have a −9.9 and 20.1 % bias, respectively. This RMP was found to have equivalent results to two other RMPs in a previous study.

Conclusions

This RMP demonstrated excellent imprecision, achieving an overall CV of 2.8 % and meeting the CV ≤6.2 % performance specification required for standardizing urine albumin measurements in clinical laboratories.

Keywords: urine albumin; LC-MS/MS; reference measurement procedure; standardization; mass spectrometry

Corresponding author: Jesse C. Seegmiller, PhD, Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA, E-mail: jseegmil@umn.edu

Funding source: National Institutes of Health National Center for Advancing Translational Sciences

Award Identifier / Grant number: Grant UM1TR004405

Acknowledgments

We acknowledge the NIDDK Urine Albumin Standardization laboratory working group along with Drs. W. Greg Miller and John H. Eckfeldt for helpful input and conversations.

Research ethics: Study was approved by the University of Minnesota Institutional Review Board and classified exempt as there were no patient identifiers obtained and specimens were deidentified.
Informed consent: Not applicable as study was classified as minimal risk and exempt by IRB.
Author contributions: JCS: Corresponding author, study design, writing, data workup and interpretation. SS: Writing, data workup, and submission. ZS: Writing and data workup. ME: Statistical advisor. 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: JCS serves as a consultant for Abbott Laboratories and Nephrolyx. All other authors state no conflict of interest.
Research funding: Statistical analysis was supported in part by the National Institutes of Health’s National Center for Advancing Translational Sciences, grant UM1TR004405. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health’s National Center for Advancing Translational Sciences.
Data availability: All data generated or analyzed during this study are included in this published article [and its Supplementary Information files].

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2024-1374).

Received: 2024-11-22

Accepted: 2025-03-25

Published Online: 2025-04-08

Published in Print: 2025-07-28

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https://doi.org/10.1515/cclm-2024-1374

Keywords for this article

urine albumin; LC-MS/MS; reference measurement procedure; standardization; mass spectrometry