Nephron. Physiology
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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.
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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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Nephron. Physiology · Jan 2014
ReviewBiomarkers in acute kidney injury: are we ready for prime time?
Novel biomarkers are required to improve the timely detection of early acute kidney injury (AKI) and to improve the differential diagnosis, prognostic assessment, and management of AKI cases. It is anticipated that novel biomarkers of early structural AKI ('acute kidney damage') will provide critical diagnostic and prognostic stratification and complement functional markers such as serum creatinine. Further studies are required to conclusively demonstrate the association between early kidney damage biomarkers and clinical outcomes, both with and independently of functional markers, and to discern whether or not randomization to a treatment for AKI based on high structural/damage biomarker levels results in an improvement in kidney function and clinical outcomes.
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Nephron. Physiology · Jan 2014
ReviewThe evolution of pediatric continuous renal replacement therapy.
The provision of continuous renal replacement therapies (CRRT) to small children has generally required the adaptation of adult machines and modified operational characteristics. CRRT prescription for younger and smaller children versus adults differs significantly due to problems concerning the extracorporeal blood volume, the need for circuit blood priming, and the adaptation of machines designed for adult-sized patients. ⋯ In 2012, a dedicated machine, i.e. the Cardio-Renal, Pediatric Dialysis Emergency Machine (CARPEDIEM), was developed and launched the 'fitted era' for pediatric CRRT. In this review, we analyze how CRRT techniques have evolved for pediatric application and describe the first in vivo application of the CARPEDIEM for the safe and efficacious provision of CRRT to infants.
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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.