Expanded renal lymphatics improve recovery following kidney injury

Abstract Acute kidney injury (AKI) is a major cause of patient mortality and a major risk multiplier for the progression to chronic kidney disease (CKD). The mechanism of the AKI to CKD transition is complex but is likely mediated by the extent and length of the inflammatory response following the i...

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Autores principales:	Gaurav Baranwal, Heidi A. Creed, Laurence M. Black, Alexa Auger, Alexander M. Quach, Rahul Vegiraju, Han E. Eckenrode, Anupam Agarwal, Joseph M. Rutkowski
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	AKI lymphangiogenesis POD‐ATTAC Proteinuria VEGF‐D VEGFR‐3 Physiology QP1-981
Acceso en línea:	https://doaj.org/article/9df51e6e7a444e208764ce246f7ac69d
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spelling	oai:doaj.org-article:9df51e6e7a444e208764ce246f7ac69d2021-11-27T15:48:30ZExpanded renal lymphatics improve recovery following kidney injury2051-817X10.14814/phy2.15094https://doaj.org/article/9df51e6e7a444e208764ce246f7ac69d2021-11-01T00:00:00Zhttps://doi.org/10.14814/phy2.15094https://doaj.org/toc/2051-817XAbstract Acute kidney injury (AKI) is a major cause of patient mortality and a major risk multiplier for the progression to chronic kidney disease (CKD). The mechanism of the AKI to CKD transition is complex but is likely mediated by the extent and length of the inflammatory response following the initial injury. Lymphatic vessels help to maintain tissue homeostasis through fluid, macromolecule, and immune modulation. Increased lymphatic growth, or lymphangiogenesis, often occurs during inflammation and plays a role in acute and chronic disease processes. What roles renal lymphatics and lymphangiogenesis play in AKI recovery and CKD progression remains largely unknown. To determine if the increased lymphatic density is protective in the response to kidney injury, we utilized a transgenic mouse model with inducible, kidney‐specific overexpression of the lymphangiogenic protein vascular endothelial growth factor‐D to expand renal lymphatics. “KidVD” mouse kidneys were injured using inducible podocyte apoptosis and proteinuria (POD‐ATTAC) or bilateral ischemia reperfusion. In the acute injury phase of both models, KidVD mice demonstrated a similar loss of function measured by serum creatinine and glomerular filtration rate compared to their littermates. While the initial inflammatory response was similar, KidVD mice demonstrated a shift toward more CD4+ and fewer CD8+ T cells in the kidney. Reduced collagen deposition and improved functional recovery over time was also identified in KidVD mice. In KidVD‐POD‐ATTAC mice, an increased number of podocytes were counted at 28 days post‐injury. These data demonstrate that increased lymphatic density prior to injury alters the injury recovery response and affords protection from CKD progression.Gaurav BaranwalHeidi A. CreedLaurence M. BlackAlexa AugerAlexander M. QuachRahul VegirajuHan E. EckenrodeAnupam AgarwalJoseph M. RutkowskiWileyarticleAKIlymphangiogenesisPOD‐ATTACProteinuriaVEGF‐DVEGFR‐3PhysiologyQP1-981ENPhysiological Reports, Vol 9, Iss 22, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	AKI lymphangiogenesis POD‐ATTAC Proteinuria VEGF‐D VEGFR‐3 Physiology QP1-981
spellingShingle	AKI lymphangiogenesis POD‐ATTAC Proteinuria VEGF‐D VEGFR‐3 Physiology QP1-981 Gaurav Baranwal Heidi A. Creed Laurence M. Black Alexa Auger Alexander M. Quach Rahul Vegiraju Han E. Eckenrode Anupam Agarwal Joseph M. Rutkowski Expanded renal lymphatics improve recovery following kidney injury
description	Abstract Acute kidney injury (AKI) is a major cause of patient mortality and a major risk multiplier for the progression to chronic kidney disease (CKD). The mechanism of the AKI to CKD transition is complex but is likely mediated by the extent and length of the inflammatory response following the initial injury. Lymphatic vessels help to maintain tissue homeostasis through fluid, macromolecule, and immune modulation. Increased lymphatic growth, or lymphangiogenesis, often occurs during inflammation and plays a role in acute and chronic disease processes. What roles renal lymphatics and lymphangiogenesis play in AKI recovery and CKD progression remains largely unknown. To determine if the increased lymphatic density is protective in the response to kidney injury, we utilized a transgenic mouse model with inducible, kidney‐specific overexpression of the lymphangiogenic protein vascular endothelial growth factor‐D to expand renal lymphatics. “KidVD” mouse kidneys were injured using inducible podocyte apoptosis and proteinuria (POD‐ATTAC) or bilateral ischemia reperfusion. In the acute injury phase of both models, KidVD mice demonstrated a similar loss of function measured by serum creatinine and glomerular filtration rate compared to their littermates. While the initial inflammatory response was similar, KidVD mice demonstrated a shift toward more CD4+ and fewer CD8+ T cells in the kidney. Reduced collagen deposition and improved functional recovery over time was also identified in KidVD mice. In KidVD‐POD‐ATTAC mice, an increased number of podocytes were counted at 28 days post‐injury. These data demonstrate that increased lymphatic density prior to injury alters the injury recovery response and affords protection from CKD progression.
format	article
author	Gaurav Baranwal Heidi A. Creed Laurence M. Black Alexa Auger Alexander M. Quach Rahul Vegiraju Han E. Eckenrode Anupam Agarwal Joseph M. Rutkowski
author_facet	Gaurav Baranwal Heidi A. Creed Laurence M. Black Alexa Auger Alexander M. Quach Rahul Vegiraju Han E. Eckenrode Anupam Agarwal Joseph M. Rutkowski
author_sort	Gaurav Baranwal
title	Expanded renal lymphatics improve recovery following kidney injury
title_short	Expanded renal lymphatics improve recovery following kidney injury
title_full	Expanded renal lymphatics improve recovery following kidney injury
title_fullStr	Expanded renal lymphatics improve recovery following kidney injury
title_full_unstemmed	Expanded renal lymphatics improve recovery following kidney injury
title_sort	expanded renal lymphatics improve recovery following kidney injury
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/9df51e6e7a444e208764ce246f7ac69d
work_keys_str_mv	AT gauravbaranwal expandedrenallymphaticsimproverecoveryfollowingkidneyinjury AT heidiacreed expandedrenallymphaticsimproverecoveryfollowingkidneyinjury AT laurencemblack expandedrenallymphaticsimproverecoveryfollowingkidneyinjury AT alexaauger expandedrenallymphaticsimproverecoveryfollowingkidneyinjury AT alexandermquach expandedrenallymphaticsimproverecoveryfollowingkidneyinjury AT rahulvegiraju expandedrenallymphaticsimproverecoveryfollowingkidneyinjury AT haneeckenrode expandedrenallymphaticsimproverecoveryfollowingkidneyinjury AT anupamagarwal expandedrenallymphaticsimproverecoveryfollowingkidneyinjury AT josephmrutkowski expandedrenallymphaticsimproverecoveryfollowingkidneyinjury
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Expanded renal lymphatics improve recovery following kidney injury

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