Microvascular endothelial injury and dysfunction during ischemic acute renal failure

Research output: Contribution to journalArticle

388 Citations (Scopus)

Abstract

The pathophysiology of ischemic acute renal failure (ARF) appears to involve a complex interplay between renal hemodynamics, tubular injury, and inflammatory processes. While the current paradigm of the pathophysiology of ischemic ARF invokes both sublethal and lethal tubular injury as being of paramount importance to diminished renal function, a growing body of evidence supports the contribution of altered renal vascular function in potentially initiating and subsequently extending the initial tubular injury. We propose that the "extension phase" of ischemic ARF involves alterations in renal perfusion, continued hypoxia, and inflammatory processes that all contribute to continued tubular cell injury. Vascular endothelial cell injury and dysfunction play a vital part in this extension phase. In the constitutive state the endothelium regulates migration of inflammatory cells into tissue, vascular tone and perfusion, vasopermeability, and prevents coagulation. Upon injury, the endothelial cell loses its ability to regulate these functions. This loss of regulatory function can have a subsequent detrimental impact upon renal function. Vascular congestion, edema formation, diminished blood flow, and infiltration of inflammatory cells have been documented in the corticomedullary junction of the kidney, but linking their genesis to vascular endothelial injury and dysfunction has been difficult. However, new investigative approaches, including multiphoton microscopy and the Tie2-GFP mouse, have been developed that will further our understanding of the roles endothelial injury and dysfunction play in the pathophysiology of ischemic ARF. This knowledge should provide new diagnostic and therapeutic approaches to ischemic ARF.

Original languageEnglish (US)
Pages (from-to)1539-1549
Number of pages11
JournalKidney international
Volume62
Issue number5
DOIs
StatePublished - Nov 2002

Fingerprint

Acute Kidney Injury
Kidney
Wounds and Injuries
Blood Vessels
Endothelial Cells
Perfusion
Vascular System Injuries
Endothelium
Cell Movement
Microscopy
Edema
Hemodynamics

Keywords

  • Acute renal failure
  • Coagulation
  • Endothelium
  • Inflammation
  • Ischemia
  • Kidney disease

ASJC Scopus subject areas

  • Nephrology

Cite this

Microvascular endothelial injury and dysfunction during ischemic acute renal failure. / Sutton, Timothy A.; Fisher, Charles J.; Molitoris, Bruce A.

In: Kidney international, Vol. 62, No. 5, 11.2002, p. 1539-1549.

Research output: Contribution to journalArticle

@article{6cffaefdcbc044e7ba571125c028d5f2,
title = "Microvascular endothelial injury and dysfunction during ischemic acute renal failure",
abstract = "The pathophysiology of ischemic acute renal failure (ARF) appears to involve a complex interplay between renal hemodynamics, tubular injury, and inflammatory processes. While the current paradigm of the pathophysiology of ischemic ARF invokes both sublethal and lethal tubular injury as being of paramount importance to diminished renal function, a growing body of evidence supports the contribution of altered renal vascular function in potentially initiating and subsequently extending the initial tubular injury. We propose that the {"}extension phase{"} of ischemic ARF involves alterations in renal perfusion, continued hypoxia, and inflammatory processes that all contribute to continued tubular cell injury. Vascular endothelial cell injury and dysfunction play a vital part in this extension phase. In the constitutive state the endothelium regulates migration of inflammatory cells into tissue, vascular tone and perfusion, vasopermeability, and prevents coagulation. Upon injury, the endothelial cell loses its ability to regulate these functions. This loss of regulatory function can have a subsequent detrimental impact upon renal function. Vascular congestion, edema formation, diminished blood flow, and infiltration of inflammatory cells have been documented in the corticomedullary junction of the kidney, but linking their genesis to vascular endothelial injury and dysfunction has been difficult. However, new investigative approaches, including multiphoton microscopy and the Tie2-GFP mouse, have been developed that will further our understanding of the roles endothelial injury and dysfunction play in the pathophysiology of ischemic ARF. This knowledge should provide new diagnostic and therapeutic approaches to ischemic ARF.",
keywords = "Acute renal failure, Coagulation, Endothelium, Inflammation, Ischemia, Kidney disease",
author = "Sutton, {Timothy A.} and Fisher, {Charles J.} and Molitoris, {Bruce A.}",
year = "2002",
month = "11",
doi = "10.1046/j.1523-1755.2002.00631.x",
language = "English (US)",
volume = "62",
pages = "1539--1549",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Microvascular endothelial injury and dysfunction during ischemic acute renal failure

AU - Sutton, Timothy A.

AU - Fisher, Charles J.

AU - Molitoris, Bruce A.

PY - 2002/11

Y1 - 2002/11

N2 - The pathophysiology of ischemic acute renal failure (ARF) appears to involve a complex interplay between renal hemodynamics, tubular injury, and inflammatory processes. While the current paradigm of the pathophysiology of ischemic ARF invokes both sublethal and lethal tubular injury as being of paramount importance to diminished renal function, a growing body of evidence supports the contribution of altered renal vascular function in potentially initiating and subsequently extending the initial tubular injury. We propose that the "extension phase" of ischemic ARF involves alterations in renal perfusion, continued hypoxia, and inflammatory processes that all contribute to continued tubular cell injury. Vascular endothelial cell injury and dysfunction play a vital part in this extension phase. In the constitutive state the endothelium regulates migration of inflammatory cells into tissue, vascular tone and perfusion, vasopermeability, and prevents coagulation. Upon injury, the endothelial cell loses its ability to regulate these functions. This loss of regulatory function can have a subsequent detrimental impact upon renal function. Vascular congestion, edema formation, diminished blood flow, and infiltration of inflammatory cells have been documented in the corticomedullary junction of the kidney, but linking their genesis to vascular endothelial injury and dysfunction has been difficult. However, new investigative approaches, including multiphoton microscopy and the Tie2-GFP mouse, have been developed that will further our understanding of the roles endothelial injury and dysfunction play in the pathophysiology of ischemic ARF. This knowledge should provide new diagnostic and therapeutic approaches to ischemic ARF.

AB - The pathophysiology of ischemic acute renal failure (ARF) appears to involve a complex interplay between renal hemodynamics, tubular injury, and inflammatory processes. While the current paradigm of the pathophysiology of ischemic ARF invokes both sublethal and lethal tubular injury as being of paramount importance to diminished renal function, a growing body of evidence supports the contribution of altered renal vascular function in potentially initiating and subsequently extending the initial tubular injury. We propose that the "extension phase" of ischemic ARF involves alterations in renal perfusion, continued hypoxia, and inflammatory processes that all contribute to continued tubular cell injury. Vascular endothelial cell injury and dysfunction play a vital part in this extension phase. In the constitutive state the endothelium regulates migration of inflammatory cells into tissue, vascular tone and perfusion, vasopermeability, and prevents coagulation. Upon injury, the endothelial cell loses its ability to regulate these functions. This loss of regulatory function can have a subsequent detrimental impact upon renal function. Vascular congestion, edema formation, diminished blood flow, and infiltration of inflammatory cells have been documented in the corticomedullary junction of the kidney, but linking their genesis to vascular endothelial injury and dysfunction has been difficult. However, new investigative approaches, including multiphoton microscopy and the Tie2-GFP mouse, have been developed that will further our understanding of the roles endothelial injury and dysfunction play in the pathophysiology of ischemic ARF. This knowledge should provide new diagnostic and therapeutic approaches to ischemic ARF.

KW - Acute renal failure

KW - Coagulation

KW - Endothelium

KW - Inflammation

KW - Ischemia

KW - Kidney disease

UR - http://www.scopus.com/inward/record.url?scp=0036406927&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036406927&partnerID=8YFLogxK

U2 - 10.1046/j.1523-1755.2002.00631.x

DO - 10.1046/j.1523-1755.2002.00631.x

M3 - Article

C2 - 12371954

AN - SCOPUS:0036406927

VL - 62

SP - 1539

EP - 1549

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 5

ER -