Pre-arrest doxycycline protects donation after circulatory death kidneys

Abstract Kidney injury during donation after circulatory determination of death (DCDD) includes warm ischemic (WI) injury from around the time of asystole, and cold ischemic (CI) injury during cold preservation. We have previously shown that Matrix Metalloproteinases (MMPs) are involved in CI injury...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Michael Moser, Sarah Schmid, Katherine Sawicka, Tamalina Banerjee, Erick McNair, Jolanta Sawicka, Iwona Bil-Lula, Grzegorz Sawicki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9d14c95998694e2fb073282f7cdcb2f0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:9d14c95998694e2fb073282f7cdcb2f0
record_format	dspace
spelling	oai:doaj.org-article:9d14c95998694e2fb073282f7cdcb2f02021-12-02T12:40:41ZPre-arrest doxycycline protects donation after circulatory death kidneys10.1038/s41598-020-79440-62045-2322https://doaj.org/article/9d14c95998694e2fb073282f7cdcb2f02020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79440-6https://doaj.org/toc/2045-2322Abstract Kidney injury during donation after circulatory determination of death (DCDD) includes warm ischemic (WI) injury from around the time of asystole, and cold ischemic (CI) injury during cold preservation. We have previously shown that Matrix Metalloproteinases (MMPs) are involved in CI injury and that Doxycycline (Doxy), an antibiotic and known MMP inhibitor, protects the transplant kidney during CI. The purpose of our study was to determine if Doxy given before asystole can also prevent injury during WI. A rat model of DCDD was used, including Control, Preemptive Doxy (45 mg/kg iv), and Preemptive and Perfusion (100 microM) Doxy groups. Thirty minutes after asystole, both kidneys were removed. The left kidney was perfused at 4 °C for 22 h, whereas the right was used to establish the degree of warm ischemic injury prior to cold preservation. MMP-2 in the perfusate was significantly reduced in both treatment groups [Control 43.7 ± 7.2 arbitrary units, versus Preemptive Doxy group 23.2 ± 5.5 (p = 0.03), and ‘Preemptive and Perfusion’ group 18.0 ± 5.6 (p = 0.02)]. Reductions in NGAL, LDH, and MMP-9 were also seen. Electron microscopy showed a marked reduction in mitochondrial injury scores in the treatment groups. Pre-arrest Doxy was associated with a reduction in injury markers and morphologic changes. Doxy may be a simple and safe means of protecting transplant kidneys from both WI and CI.Michael MoserSarah SchmidKatherine SawickaTamalina BanerjeeErick McNairJolanta SawickaIwona Bil-LulaGrzegorz SawickiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-9 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michael Moser Sarah Schmid Katherine Sawicka Tamalina Banerjee Erick McNair Jolanta Sawicka Iwona Bil-Lula Grzegorz Sawicki Pre-arrest doxycycline protects donation after circulatory death kidneys
description	Abstract Kidney injury during donation after circulatory determination of death (DCDD) includes warm ischemic (WI) injury from around the time of asystole, and cold ischemic (CI) injury during cold preservation. We have previously shown that Matrix Metalloproteinases (MMPs) are involved in CI injury and that Doxycycline (Doxy), an antibiotic and known MMP inhibitor, protects the transplant kidney during CI. The purpose of our study was to determine if Doxy given before asystole can also prevent injury during WI. A rat model of DCDD was used, including Control, Preemptive Doxy (45 mg/kg iv), and Preemptive and Perfusion (100 microM) Doxy groups. Thirty minutes after asystole, both kidneys were removed. The left kidney was perfused at 4 °C for 22 h, whereas the right was used to establish the degree of warm ischemic injury prior to cold preservation. MMP-2 in the perfusate was significantly reduced in both treatment groups [Control 43.7 ± 7.2 arbitrary units, versus Preemptive Doxy group 23.2 ± 5.5 (p = 0.03), and ‘Preemptive and Perfusion’ group 18.0 ± 5.6 (p = 0.02)]. Reductions in NGAL, LDH, and MMP-9 were also seen. Electron microscopy showed a marked reduction in mitochondrial injury scores in the treatment groups. Pre-arrest Doxy was associated with a reduction in injury markers and morphologic changes. Doxy may be a simple and safe means of protecting transplant kidneys from both WI and CI.
format	article
author	Michael Moser Sarah Schmid Katherine Sawicka Tamalina Banerjee Erick McNair Jolanta Sawicka Iwona Bil-Lula Grzegorz Sawicki
author_facet	Michael Moser Sarah Schmid Katherine Sawicka Tamalina Banerjee Erick McNair Jolanta Sawicka Iwona Bil-Lula Grzegorz Sawicki
author_sort	Michael Moser
title	Pre-arrest doxycycline protects donation after circulatory death kidneys
title_short	Pre-arrest doxycycline protects donation after circulatory death kidneys
title_full	Pre-arrest doxycycline protects donation after circulatory death kidneys
title_fullStr	Pre-arrest doxycycline protects donation after circulatory death kidneys
title_full_unstemmed	Pre-arrest doxycycline protects donation after circulatory death kidneys
title_sort	pre-arrest doxycycline protects donation after circulatory death kidneys
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/9d14c95998694e2fb073282f7cdcb2f0
work_keys_str_mv	AT michaelmoser prearrestdoxycyclineprotectsdonationaftercirculatorydeathkidneys AT sarahschmid prearrestdoxycyclineprotectsdonationaftercirculatorydeathkidneys AT katherinesawicka prearrestdoxycyclineprotectsdonationaftercirculatorydeathkidneys AT tamalinabanerjee prearrestdoxycyclineprotectsdonationaftercirculatorydeathkidneys AT erickmcnair prearrestdoxycyclineprotectsdonationaftercirculatorydeathkidneys AT jolantasawicka prearrestdoxycyclineprotectsdonationaftercirculatorydeathkidneys AT iwonabillula prearrestdoxycyclineprotectsdonationaftercirculatorydeathkidneys AT grzegorzsawicki prearrestdoxycyclineprotectsdonationaftercirculatorydeathkidneys
_version_	1718393755101298688

Pre-arrest doxycycline protects donation after circulatory death kidneys

Ejemplares similares