Nephron. Physiology
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Nephron. Physiology · Jan 2014
ReviewRole of renal oxygenation and mitochondrial function in the pathophysiology of acute kidney injury.
There are unique features of renal oxygenation that render the kidney susceptible to oxygen demand-supply mismatch and hypoxia. Renal oxygen consumption by oxidative metabolism is closely coupled to and driven by tubular transport, which is linked to the filtered solute load and glomerular filtration rate (GFR). In turn, filtered solute load and GFR are dependent on the renal blood flow. ⋯ Here we review the published literature characterizing renal oxygenation and mitochondrial function in ischemic and sepsis-associated acute kidney injury (AKI). However, the coupling of transport and metabolism in AKI has not been examined. This is a potentially fruitful area of research that should become increasingly active given the emerging data linking renal oxygenation and hypoxia to acute and chronic dysfunction in the kidney.
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Nephron. Physiology · Jan 2014
ReviewThe potential of alkaline phosphatase as a treatment for sepsis-associated acute kidney injury.
Sepsis-associated acute kidney injury (AKI) is associated with a high attributable mortality and an increased risk of developing chronic kidney failure in survivors. As a successful therapy is, as yet, unavailable, a pharmacological treatment option is clearly warranted. Recently, two small phase II clinical trials demonstrated beneficial renal effects of bovine-derived alkaline phosphatase administration in critically ill patients with sepsis-associated AKI. ⋯ Another target of alkaline phosphatase could be adenosine triphosphate, a proinflammatory mediator released during cellular stress, which can be converted by alkaline phosphatase into the tissue-protective and anti-inflammatory molecule adenosine. Human recombinant alkaline phosphatase, a recently developed replacement for bovine-derived alkaline phosphatase, has shown promising results in the preclinical phase. As its safety and tolerability were recently confirmed in a phase I clinical trial, the renal protective effect of human recombinant alkaline phosphatase in sepsis-associated AKI shall be investigated in a multicenter phase II clinical trial starting at the end of this year.
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Nephron. Physiology · Jan 2014
ReviewTargeting recovery from acute kidney injury: incidence and prevalence of recovery.
Since the creation of Risk, Injury, Failure, Loss of Kidney Function, and End-Stage Renal Disease (RIFLE) criteria in the last 10 years, the use of a standardized definition of acute kidney injury (AKI) has made it possible for epidemiologic studies to document the increasing incidence of AKI, especially in the critical care setting. In addition, several studies applying the criteria of RIFLE, Acute Kidney Injury Network, and, more recently, the Kidney Disease: Improving Global Outcome, were able to establish the association of severity of AKI with adverse clinical outcomes, including the development of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Although, until recently, it was thought that survivors from an AKI episode frequently recover kidney function, cumulative observational data over the past decade have confirmed the association of AKI with the increased risk for permanent kidney damage, with subsequent development of CKD. The epidemiological studies that we will present and discuss in this review confirm and clarify the association of AKI with the development of CKD and ESRD.
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Nephron. Physiology · Jan 2014
ReviewProgression from acute kidney injury to chronic kidney disease: clinical and experimental insights and queries.
There is an increasing number of clinical studies suggesting that acute kidney injury (AKI) can be complicated by the onset of progressive renal disease. Indeed, given the frequency of AKI in hospitalized patients, it could potentially be a leading cause of, or contributor to, end-stage renal disease. Insights into the natural history of AKI and potential mechanisms for disease progression can be gleaned from experimental studies. ⋯ Indeed, in the aftermath of AKI, a variety of secondary renal protective pathways are activated, which may retard or prevent severe chronic kidney disease. Furthermore, the onset of acute uremia per se may exert surprisingly potent renal protective effects. The purpose of this brief report is to review some of the clinical and experimental data that deal with these complex issues.
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Nephron. Physiology · Jan 2014
Observational StudyAssociation of de novo dipstick albuminuria with severe acute kidney injury in critically ill septic patients.
Acute kidney injury (AKI) occurs frequently in septic patients. Albuminuria may play a role as an early marker of septic AKI. The potential association between de novo dipstick albuminuria (DA) and septic AKI has not been examined. ⋯ De novo DA within the first 24 h of admission was independently associated with severe AKI in critically ill septic patients. Future studies are required to fully elucidate the utility of DA testing in the early detection and stratification of AKI.