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Caveolin-1 in situ expression in glomerular and peritubular capillaries as a marker of ultrastructural progression and severity of renal thrombotic microangiopathy

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Abstract

Background

Thrombotic microangiopathy is a severe and potentially life-threatening condition inducing severe endothelial injury in many organs, particularly native and transplanted kidneys. Current pathological studies by our group have identified the use of Caveolin-1 immunohistochemistry as a potential marker of endothelial damage and progression degree of thrombotic microangiopathy. The aim of the present work was to evaluate Caveolin-1 as a marker of severity in thrombotic microangiopathy kidney disease, according to the ultrastructural progression of the disease evaluated by transmission electron microscopy.

Materials and methods

Twenty-nine patients (17 non-transplanted and 12 transplanted) were retrospectively selected, biopsied for suspected or histologically-confirmed thrombotic microangiopathy. Transmission electron microscopy was performed in all cases, and an ultrastructural score of thrombotic microangiopathy-related glomerular disease was assessed (from 0 to 3+). Immunohistochemistry for Caveolin-1 was automatically performed.

Results

The mean percentage of Caveolin-1-positive glomerular capillaries was 53.2 ± 40.6% and 28.0 ± 42.8% in the active thrombotic microangiopathy versus previous thrombotic microangiopathy cases (p = 0.085), considering both native and transplanted kidneys. The presence of progressive disease correlated with diffuse Caveolin-1 immunoreactivity (p = 0.031), and ultrastructural score correlated with glomerular Caveolin-1 positivity, progressively increasing from 22.5% of the Score 0 group to 95.5% of the Score 3 group (p = 0.036).

Discussion

Caveolin-1 proved to be a very useful marker of early endothelial damage in the course of thrombotic microangiopathy for both native and transplanted kidneys, therefore worth considering in routine practice. Diffuse glomerular Caveolin-1 immunoreactivity correlates with the severity of the thrombotic disease and it can appear very early, even before ultrastructurally evident endothelial damage.

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Data availability

The data used and analyzed in this study are available from the corresponding author on reasonable request.

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Funding

The work reported in this publication was funded by the Italian Ministry of Health, RC-2022-2773443.

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Correspondence to Francesco Vasuri.

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All the procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki Declaration and its later amendments.

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Vasuri, F., Lisi, A.P., Ciavarella, C. et al. Caveolin-1 in situ expression in glomerular and peritubular capillaries as a marker of ultrastructural progression and severity of renal thrombotic microangiopathy. J Nephrol 36, 2327–2333 (2023). https://doi.org/10.1007/s40620-023-01645-5

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