Pathophysiology of Acute Kidney Injury
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TLDR
The successful recovery from AKI depends on the degree to which repair processes ensue and these may be compromised in elderly or chronic kidney disease (CKD) patients, so targeting the extension phase of treatment with the greatest possible impact is suggested.Abstract:
Acute kidney injury (AKI) is the leading cause of nephrology consultation and is associated with high mortality rates. The primary causes of AKI include ischemia, hypoxia or nephrotoxicity. An underlying feature is a rapid decline in GFR usually associated with decreases in renal blood flow. Inflammation represents an important additional component of AKI leading to the extension phase of injury, which may be associated with insensitivity to vasodilator therapy. It is suggested that targeting the extension phase represents an area potential of treatment with the greatest possible impact. The underlying basis of renal injury appears to be impaired energetics of the highly metabolically active nephron segments (i.e., proximal tubules and thick ascending limb) in the renal outer medulla, which can trigger conversion from transient hypoxia to intrinsic renal failure. Injury to kidney cells can be lethal or sublethal. Sublethal injury represents an important component in AKI, as it may profoundly influence GFR and renal blood flow. The nature of the recovery response is mediated by the degree to which sublethal cells can restore normal function and promote regeneration. The successful recovery from AKI depends on the degree to which these repair processes ensue and these may be compromised in elderly or CKD patients. Recent data suggest that AKI represents a potential link to CKD in surviving patients. Finally, earlier diagnosis of AKI represents an important area in treating patients with AKI that has spawned increased awareness of the potential that biomarkers of AKI may play in the future.read more
Citations
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Mitochondrial energetics in the kidney
TL;DR: Implementing compounds that stimulate mitochondrial biogenesis can restore mitochondrial and renal function in mouse models of AKI and diabetes mellitus and inhibiting the fission protein dynamin 1-like protein (DRP1) might ameliorate ischaemic renal injury by blocking mitochondrial fission.
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Failed Tubule Recovery, AKI-CKD Transition, and Kidney Disease Progression
TL;DR: Experiments using an acute-on-chronic injury model suggest that additional loss of parenchyma caused by failed repair of AKI in kidneys with prior renal mass reduction triggers hemodynamically mediated processes that damage glomeruli to cause progression.
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Heart failure and kidney dysfunction: epidemiology, mechanisms and management
TL;DR: Important crosstalk between the heart and kidney is described, with a focus on HF and kidney disease in the acute and chronic settings, and underlying molecular and cellular pathomechanisms in HF, AKI and CKD are discussed in addition to current and future therapeutic approaches.
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Molecular optical imaging probes for early diagnosis of drug-induced acute kidney injury
TL;DR: MRPs in situ report the sequential occurrence of oxidative stress, lysosomal damage and cellular apoptosis, which precedes clinical manifestation of AKI (decreased glomerular filtration), allowing MRPs to non-invasively detect the onset of cisplatin-induced AKI at least 36 h earlier than the existing imaging methods.
Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes.
TL;DR: The view for AKI is beginning to change from a single organ failure syndrome to a syndrome where the kidney plays an active role in the progress of multi-organ dysfunction.
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