Kidney Function and Urine LAM Detection in HIV-Negative Adults with Pulmonary Tuberculosis Disease

Abstract

Background: Urine lipoarabinomannan (uLAM) is a glycolipid biomarker for tuberculosis (TB) disease in resource-limited settings, and uLAM testing is approved for use in people living with HIV (PLHIV). uLAM is detectable among HIV-negative adults, and the impact of kidney function on uLAM detectability remains unclear. We investigated the association between estimated glomerular filtration rate (eGFR), a measure of kidney function, and uLAM detection in patients with microbiologically confirmed pulmonary TB disease (PTB). Methods: Adults with presumptive TB disease were enrolled in a diagnostic cohort study at the National Lung Hospital in Hanoi, Vietnam, between October 2021 and April 2022. Each participant provided two sputum samples—one tested with Xpert MTB/RIF Ultra and the other with Mycobacterial Growth Indicator Tube (MGIT) culture—to confirm pulmonary TB (PTB) microbiologically. We restricted analyses to HIV-negative adults who provided a urine specimen for testing. We calculated eGFR using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and determined uLAM positivity by an electrochemiluminescence assay (S4-20: A194-01 antibody pair). Univariate analyses were conducted to evaluate associations between participant characteristics and uLAM positivity, while multivariable logistic regression was used to assess the relationship between eGFR and uLAM positivity, adjusting for key covariates. Results: Among 780 enrolled participants, mean age was 44 years, 72.5% were male, and 324 (41.5%) had microbiologically confirmed PTB. Among 324 adults with PTB, 57 participants (17.6%) had decreased renal function (eGFR <90 mL/min/1.73ml). In univariate analysis, higher HbA1c levels (OR = 1.22, 95% CI: 1.07–1.41), urine protein positivity (OR = 2.37, 95% CI: 1.27–4.46), and sputum smear positivity (OR for 3+ vs. smear-negative = 8.43, 95% CI: 2.78–31.47) were significantly associated with uLAM positivity. In multivariable analysis, sputum smear grade (aOR for 3+ = 6.96, 95% CI: 2.21–26.58) and HbA1c (aOR = 1.18, 95% CI: 1.03–1.38) remained significant predictors of uLAM positivity. eGFR was not significantly associated with uLAM positivity in either the univariate analyses or multivariable models. Conclusion: Among HIV-negative adults with microbiologically confirmed PTB in Vietnam, uLAM detectability was associated with bacillary load and diabetes status. Kidney function, as measured by eGFR, was not a significant determinant of uLAM positivity. uLAM testing may be suitable for HIV-negative people with acute kidney injury or chronic kidney disease in resource-limited settings.