Molecular mechanisms of acute renal failure following ischemia/reperfusion.
Acute renal failure (ARF) necessitating renal replacement therapy is a common problem associated with high morbidity and mortality in the critically ill. Hypotension, followed by resuscitation, is the most common etiologic factor, mimicked by ischemia/reperfusion (I/R) in animal models. Although knowledge of the pathophysiology of ARF in the course of this condition is increasingly detailed, the intracellular and molecular mechanisms leading to ARF are still incompletely understood. This review aims at describing the role of cellular events and signals, including collapse of the cytoskeleton, mitochondrial and nuclear changes, in mediating cell dysfunction, programmed cell death (apoptosis), necrosis and others. Insight into the molecular pathways in the various elements of the kidney, such as vascular endothelium and smooth muscle and tubular epithelium leading to cell damage upon I/R will, hopefully, open new therapeutic modalities, to mitigate the development of ARF after hypotensive episodes and to promote repair and resumption of renal function once ARF has developed.
Versteilen
A M G
AM
Department of Physiology, Institute for Cardiovascular Research, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands.
Di Maggio
F
F
Leemreis
J R
JR
Groeneveld
A B J
AB
Musters
R J P
RJ
Sipkema
P
P
D000199:Actins; D058186:Acute Kidney Injury / Q000503:physiopathology* / Q000517:prevention & control; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000098:blood supply*; D007684:Kidney Tubules / Q000502:physiology; D009336:Necrosis / Q000503:physiopathology; D009504:Neutrophils / Q000502:physiology; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000199:Actins; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha