Avaliação da nefrina e podocina como biomarcadores precoces de proteinúria associada ao uso de inibidores do mTOR em pacientes transplantados renais
Albuminuria is the main clinical manifestation of glomerular damage (GD) following renal transplantation (KTx). It can be induced by the use of mammalian target of rapamycin inhibitors (mTORi). Since GD starts from podocyte injury, proteins of these cells found in urinary extracellular vesicles (...
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| Formato: | doctoralThesis |
| Idioma: | pt_BR |
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Brasil
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| Endereço do item: | https://repositorio.ufrn.br/jspui/handle/123456789/26924 |
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| Resumo: | Albuminuria is the main clinical manifestation of glomerular damage (GD) following
renal transplantation (KTx). It can be induced by the use of mammalian target of
rapamycin inhibitors (mTORi). Since GD starts from podocyte injury, proteins of these
cells found in urinary extracellular vesicles (uEVs), such as nephrin and podocin, are
potential biomarkers for early GD evaluation. Therefore, the objectives of this study
were: to evaluate the expression of nephrin and podocin in uEVs of KTx patients with
or without mTORi treatment for immunosuppression, for a period of 12-months, and to
evaluate the use of these proteins as specific biomarkers of GD. Thus, 47 KTx patients
were recruited and distributed in two groups according to mTORi use (non-mTORi and
mTORi groups). The expression of nephrin and podocin was measured at 3, 6, 9 and
12-months post-KTx. Increased values of urinary nephrin/creatinine and
podocin/creatinine ratios were found in the mTORi group [3 (p = 0.004), 6 (p = 0.009)
and 9-months (p = 0.001); and 3 (p = 0.002), 6 (p = 0.030) and 9-months (p <0.001)
post-KTx, respectively] when compared to the corresponding values in the non-mTORi
group. Patients of the mTORi group, who presented with nephrinuria and podocinuria
3-months post-KTx had a glomerular filtration rate (GFR) lower than 42 mL/min/1.73
m2
in all follow-up periods. In the ROC (receiver operating characteristic curve)
analysis, it was observed that the nephrin/creatinine and podocin/creatinine ratios
presented high AUROC (area under the ROC) values for prediction of proteinuria
development and GFR <60 mL/min/1.73 m2
. In summary, this study is the first to show
increased expression of nephrin and podocin released in uEVs in patients using
mTORi 3-months post-KTx, while albumin/creatinine ratio was only increased after 9-
months of KTx. Thus, nephrin and podocin, obtained from uEVs, can become an
important diagnostic tool for the early detection of GD in KTx patients. |
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