المؤلفون: Saddadi, Fereshteh, Fallahkohan, Mohammad Hassan

المصدر: Journal of Nephropathology; Jan2022, Vol. 11 Issue 1, p1-3, 3p

مصطلحات موضوعية: KIDNEY transplantation, EVEROLIMUS, GRAFT survival, IMMUNOSUPPRESSIVE agents, MTOR inhibitors

مستخلص: Choice of maintenance immunosuppressive therapy after renal transplantation is important for graft survival. However, complication may also occur. Venous thromboembolic event with the mTOR inhibitor (mTORi) everolimus is a rare but life-threatening complication. Here we describe a renal transplant recipient who developed pulmonary thromboembolism. [ABSTRACT FROM AUTHOR]

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المؤلفون: Sagar Bhayana, Arpita Baisantry, Thomas D. Kraemer, Christoph Wrede, Jan Hegermann, Jan-Hinrich Bräsen, Clemens Bockmeyer, Jan Ulrich Becker, Matthias Ochs, Wilfried Gwinner, Hermann Haller, Anette Melk, Roland Schmitt

المصدر: Journal of Nephropathology, Vol 6, Iss 2, Pp 90-96 (2017)

مصطلحات موضوعية: autophagy, mtor inhibitors, sirolimus, kidney transplant biopsy, electron microscopy, Pathology, RB1-214, Internal medicine, RC31-1245, Other systems of medicine, RZ201-999

الوصف: Background: Mammalian target of rapamycin (mTOR) inhibitors are increasingly used as immunosuppressive agents in kidney transplantation. In the experimental setting it has been shown that mTOR inhibitors promote autophagy, but the concept that this might also occur in transplant patients has not been addressed. Objectives: This study was designed to investigate the association between mTOR inhibition and autophagy in renal transplants under routine clinical conditions. Materials and Methods: Protocol transplant biopsies of patients receiving sirolimus were compared to biopsies of patients treated without mTOR inhibitor. Electron microscopy was used for quantitative stereological analysis of autophagosomal volume fractions. Ultrastructural analysis was focused on podocytes to avoid cell type bias. Autophagy-related gene products were profiled by QPCR from laser assisted microdissected glomeruli and by immunohistochemistry for semiquantitative evaluation. Results: By electron microscopy, we observed a significant > 50% increase in podocytic autophagosomal volume fractions in patients treated with sirolimus. Evaluation of biopsy material from the same patients using transcriptional profiling of laser capture microdissected glomeruli revealed no differences in autophagy-related gene expressions. Immunohistochemical evaluation of autophagic degradation product p62 was also unaltered whereas a significant increase was observed in podocytic LC3 positivity in biopsies of sirolimus treated patients. Conclusions: These results indicate an association of sirolimus treatment and autophagosome formation in transplant patients. However, they might reflect autophagosomal buildup rather than increased autophagic flux. Further research is needed to investigate the potential functional consequences in short- and long-term outcome of patients treated with mTOR inhibitors.

وصف الملف: electronic resource

العلاقة: https://nephropathol.com/PDF/JNP-6-90.pdfTest; https://doaj.org/toc/2251-8363Test; https://doaj.org/toc/2251-8819Test

الوصول الحر: https://doaj.org/article/a24dac7d3a9a4cadb7e13dfea9524f98Test

المؤلفون: Jan Hegermann, Hermann Haller, Wilfried Gwinner, Roland Schmitt, Anette Melk, Matthias Ochs, Sagar Bhayana, Jan-Hinrich Bräsen, Arpita Baisantry, Clemens L. Bockmeyer, Christoph Wrede, Jan U. Becker, Thomas Kraemer

المصدر: Journal of Nephropathology

مصطلحات موضوعية: 0301 basic medicine, mTOR inhibitors, Cell type, Pathology, medicine.medical_specialty, 03 medical and health sciences, Autophagy, Electron microscopy, medicine, PI3K/AKT/mTOR pathway, Kidney transplantation, Sirolimus, Kidney, Kidney transplant biopsy, business.industry, Discovery and development of mTOR inhibitors, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Nephrology, Immunohistochemistry, Original Article, business, medicine.drug

الوصف: Background: Mammalian target of rapamycin (mTOR) inhibitors are increasingly used as immunosuppressive agents in kidney transplantation. In the experimental setting it has been shown that mTOR inhibitors promote autophagy, but the concept that this might also occur in transplant patients has not been addressed. Objectives: This study was designed to investigate the association between mTOR inhibition and autophagy in renal transplants under routine clinical conditions. Materials and Methods: Protocol transplant biopsies of patients receiving sirolimus were compared to biopsies of patients treated without mTOR inhibitor. Electron microscopy was used for quantitative stereological analysis of autophagosomal volume fractions. Ultrastructural analysis was focused on podocytes to avoid cell type bias. Autophagy-related gene products were profiled by QPCR from laser assisted microdissected glomeruli and by immunohistochemistry for semiquantitative evaluation. Results: By electron microscopy, we observed a significant > 50% increase in podocytic autophagosomal volume fractions in patients treated with sirolimus. Evaluation of biopsy material from the same patients using transcriptional profiling of laser capture microdissected glomeruli revealed no differences in autophagy-related gene expressions. Immunohistochemical evaluation of autophagic degradation product p62 was also unaltered whereas a significant increase was observed in podocytic LC3 positivity in biopsies of sirolimus treated patients. Conclusions: These results indicate an association of sirolimus treatment and autophagosome formation in transplant patients. However, they might reflect autophagosomal buildup rather than increased autophagic flux. Further research is needed to investigate the potential functional consequences in short- and long-term outcome of patients treated with mTOR inhibitors.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ade0f254f6ce4b8526013ecec146a45eTest
https://doi.org/10.15171/jnp.2017.15Test

المؤلفون: Fereshteh Saddadi, Mohammad Hassan Fallahkohan

المصدر: Journal of Nephropathology. 11:e11-e11

مصطلحات موضوعية: medicine.medical_specialty, Everolimus, business.industry, medicine.disease, Discovery and development of mTOR inhibitors, Surgery, Transplantation, surgical procedures, operative, Pulmonary Thromboembolisms, Nephrology, Renal transplant, medicine, Graft survival, business, Complication, Kidney transplantation, medicine.drug

الوصف: Choice of maintenance immunosuppressive therapy after renal transplantation is important for graft survival. However, complication may also occur. Venous thromboembolic event with the mTOR inhibitor (mTORi) everolimus is a rare but life-threatening complication. Here we describe a renal transplant recipient who developed pulmonary thromboembolism.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::2c3b6354378d18bb0e609c5f69a8f00bTest
https://doi.org/10.34172/jnp.2022.11Test