Urine biomarkers of pulmonary tuberculosis

ABSTRACT

Introduction

Sputum-based tuberculosis diagnosis does not address the needs of certain categories of patients. Active development of a noninvasive urine-based diagnosis could provide an alternative approach. We reviewed publications covering more than 30 urine biomarkers proposed as significant for TB diagnosis. Analytical approaches were heterogeneous in design and methods; few studies on diagnostic outcome prediction described a formal specificity and sensitivity analysis.

Areas covered

This review describes studies of non-sputum diagnostic approaches of pulmonary TB based on urine using specific TB biomarkers. The search was performed until December 2021, using terms [Tuberculosis] + [urine] + [biomarkers] in PubMed and Cochrane databases. Publications concerning LAM urine diagnostics were excluded as they have been described elsewhere.

Expert opinion

Microbiological culture of sputum is considered to be the ‘gold standard’ diagnostic for pulmonary TB but the methodology is slow due to the slow growth of the TB bacteria. Urine provides a large volume of sample. Investigators have evaluated urine for either TB pathogen biomarkers or host biomarkers with some success as the review demonstrates. Detection sensitivity remains a significant problem. In future, combination of host and pathogen biomarkers could increase the sensitivity and specificity of TB diagnosis.

KEYWORDS:

• Urine biomarkers
• tuberculosis diagnostic
• treatment efficiency predictors
• spectrometry

Article highlights

• Urine transrenal DNA extraction continues to be studied but its sensitivity and specificity depend heavily on the extraction methodologies, and patient HIV status. Sensitivity in studies varied from 29 to 79%, specificity from 67% to 100%.

• Increasing evidence suggests that the promising IP-10 TB biomarker is likely to be primarily a non-specific inflammatory marker; however, its level correlates with TB/HIV status and it may be useful to assess TB treatment response.

• Mass-spectroscopic approaches were used in numerous untargeted studies to detect mostly metabolomic and proteomic biomarkers from urine for diagnostic purposes.

• There is a lack of good biomarkers to predict TB treatment outcome.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was funded by the grant of the Ministry of Education and Science of the Russian Federation (a unique project identifier RFMEFI61019X0020, agreement number is 075-15-2019-006) and by the European Union Horizon 2020 program (Research and Innovation program under project CARE: Grant Agreement No 825673).