Is Urinary Lipoarabinomannan the Result of Renal Tuberculosis? Assessment of the Renal Histology in an Autopsy Cohort of Ugandan HIV-Infected Adults

Abstract

ObjectiveThe detection of urinary lipoarabinomannan (LAM), a mycobacterial cell wall component, is used to diagnose tuberculosis (TB). How LAM enters the urine is not known. To investigate if urinary LAM-positivity is the result of renal TB infection we correlated the outcomes of urinary LAM-antigen testing to renal histology in an autopsy cohort of hospitalized, Ugandan, HIV-infected adults.MethodsWe performed a complete autopsy, including renal sampling, in HIV-infected adults that died during hospitalization after written informed consent was obtained from the next of kin. Urine was collected postmortem through post-mortem catheterisation or by bladder puncture and tested for LAM with both a lateral flow assay (LFA) and an ELISA assay. Two pathologists assessed the kidney histology. We correlated the LAM-assay results and the histology findings.ResultsOf the 13/36 (36%) patients with a positive urinary LAM ELISA and/or LFA, 8/13 (62%) had renal TB. The remaining 5 LAM-positive patients had disseminated TB without renal involvement. Of the 23 LAM-negative patients, 3 had disseminated TB without renal involvement. The remaining LAM-negative patients had no TB infection and died mostly of fungal and bacterial infections. LAM LFA had a sensitivity of 81% and specificity of 100% to diagnose TB at any location, and the LAM ELISA a sensitivity of 63% and a specificity of 100%. 54% (7/13) LAM LFA-positive patients were not on anti-TB treatment at the time of death.ConclusionRenal TB infection explained LAM-positivity in the majority of patients. Patients with disseminated TB without renal involvement can also be diagnosed with LAM. This suggests that other mechanisms that lead to urinary LAM-positivity exist in a minority of patients.

Point-Of-Care Urine LAM Tests for Tuberculosis Diagnosis: A Status Update

“…As replicating Mtb degrades, LAM circulating in the blood is filtered across the glomerular basement membrane of the kidneys into urine (Figure 1). The presence of LAM in urine can also be a result of renal Mtb infection, as has been shown in autopsy studies [16]. Table 1.…”

“…There is evidence that HIV/TB co-infected patients with immunosuppression and disseminated TB have higher LAM concentrations in their urine [37]. Biological mechanisms to explain this are not fully understood; whether this is due to an overall higher bacterial body burden or renal TB infection is unclear [16,38]. While HIV co-infection or urinary tract disease are not necessary for LAM antigenuria, they both can lead to higher urine LAM concentrations.…”

Detection of lipoarabinomannan (LAM) in urine is indicative of disseminated TB with renal involvement in patients living with HIV and advanced immunodeficiency: evidence and implications

“…Cox et al demonstrated histological evidence of renal TB in the majority of deceased patients with LAM detected in their urine. 17 All LAM-positive patients had evidence of either renal or disseminated TB. Renal TB is also frequently found in cadavers of adults with disseminated TB at post-mortem, typically being seen in more than 50% of such cases.…”

“… 14 Whilst glomerular dysfunction might hypothetically allow LAM-containing-complexes to pass into the urine, clinical studies have not found associations between urine-LAM detection and proteinuria (a marker for glomerular damage), 15 , 16 and there is no histological evidence of glomerular damage at autopsy in patients who were urine-LAM positive. 17 …”

Feasibility of using Determine TB-LAM to diagnose tuberculosis in HIV-positive patients in programmatic conditions: a multisite study

“…The Determine TB LAM Ag test (Determine TB-LAM Ag test, Abbott, Waltham, MA, USA [formerly Alere]; LAM test) is a lateral flow assay for urinary Lipoarabinomannan (LAM) that can detect active TB within 30 min. LAM is useful in HIVpositive individuals with advanced immunodeficiency [5,6]. The World Health Organization (WHO) currently recommends the use of the LAM test to assist in the diagnosis of TB in HIVpositive patients with CD4 counts less than or equal to 100 cells/µl or in severely ill HIV-positive patients, regardless of the CD4 count, or in those with an unknown CD4 count [7].…”