Nephron. Physiology
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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
ReviewEffects of renal replacement therapy on renal recovery after acute kidney injury.
Recovery of kidney function following an episode of acute kidney injury (AKI) is now acknowledged as a vital patient-centered outcome with clear health economic implications. In approximately 5-8% of critically ill patients with more severe forms of AKI, support with renal replacement therapy (RRT) is provided. Recent data have suggested that rates of RRT utilization in AKI are increasing. ⋯ Limited data have evaluated the impact of membrane flux properties on recovery. Preliminary data have suggested that circuit anticoagulation with citrate, which results in a reduction in membrane-induced oxidative stress and leukocyte activation, may be associated with improved recovery; however, further corroborative data are needed. Additional evidence, ideally from randomized trials, is clearly needed to inform best practice in the delivery of acute RRT to optimize probability of recovery of kidney function for survivors of AKI.
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Recent progress in biomarkers represents a paradigm shift in acute kidney injury (AKI) research. Most studies have evaluated the use of these biomarkers for early diagnosis of AKI. However, the role of novel biomarkers in predicting renal recovery, though less understood, holds great clinical promise. ⋯ The biology of renal recovery requires the repopulation by surviving renal tubular epithelial cells with the assistance of certain renal epithelial cell and specific growth factors such as neutrophil gelatinase-associated lipocalin (NGAL), hepatocyte growth factor (HGF), epidermal growth factor, and insulin-like growth factor-1 (IGF-1), etc. These markers play a major role in the recovery process. This review will describe the mechanisms of the renal recovery, epidemiology, the role of conventional clinical predictors and finally the role of novel biomarkers (NGAL, HGF, IL-8, IL-18, TNFR-1, IGF-binding protein-7 and tissue inhibitor of metalloproteinase-2) in predicting renal recovery.
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Nephron. Physiology · Jan 2014
ReviewThe central role of renal microcirculatory dysfunction in the pathogenesis of acute kidney injury.
Acute kidney injury (AKI) is a rapidly developing condition often associated with critical illness, with a high degree of morbidity and mortality, whose pathophysiology is ill understood. Recent investigations have identified the dysfunction of the renal microcirculation and its cellular and subcellular constituents as being central to the etiology of AKI. ⋯ Effective therapies expected to resolve AKI will have to control inflammation and restore this homeostasis. In order to apply and guide these therapies effectively, diagnostic tools aimed at physiological biomarkers of AKI for monitoring renal microcirculatory function in advance of changes in pharmacological biomarkers associated with structural damage of the kidney will need to be developed.
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The development and use of consensus criteria for acute kidney injury (AKI) diagnosis and the inclusion of recently identified markers of renal parenchymal damage as endpoints in clinical trials have improved the ability of physicians to compare the incidence and severity of AKI across patient populations, provided targets for testing new treatments, and may increase insight into the mechanisms of AKI. To date, these markers have not consistently translated into important clinical outcomes. Is that because these markers of renal injury/dysfunction are measurements of process of care (and not indicative of persistently impaired renal function), or is it because patients do actually recover from AKI? Physicians currently have limited ability to measure renal function reserve, and the ultimate consequence of a case of AKI on long-term morbidity remains unclear. ⋯ Primary endpoints for phase I and II clinical trials, on the other hand, should continue to use continuous markers of renal injury/dysfunction as well as 'hard' clinical outcomes in order to generate meaningful data with limited subject exposure to untested treatments. By doing so, investigators may assess safety without requiring large sample sizes, demonstrate treatment effect of an unknown therapeutic, and power subsequent studies. In contrast, phase III trials should include consensus AKI criteria and more important subsequent clinical outcomes, such as MAKE90, as primary endpoints.