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

Abstract

Objective: The 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.

Methods: We 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.

Results: Of 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.

Conclusion: Renal 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.

Fig 1. Macro-and microscopic images of TB in the kidney.

A. Nodules on outer surface of the right kidney and B. in the kidney parenchyma C. Tuberculoma in the kidney parenchyma D. Ziehl-Neelsen stain of a granuloma in the renal parenchyma showing glomeruli and tubules (x5) E. Microscopic zoom of indicated area with a glomerulus and multiple acid fast bacilli (x40) F. Microscopic zoom of indicated area with multiple acid fast bacilli (x100).

Fig 2. Mechanisms leading to lipoarabinomannan antigenuria.

1. Renal TB 2. Passage of whole Mycobacterium tuberculosis through the glomerular basement membrane into the urine 3. Passage of LAM captured by immune-complexes through the glomerular basement membrane into the urine 4. Passage of uncomplexed LAM through the glomerular basement membrane into the urine 5. Impaired tubular resorption of uncomplexed LAM 6. Genital tract TB (Fig. based on [21]). MTB: Mycobacterium tuberculosis; GBM: glomerular basement membrane; LAM: lipoarabinomannan.