Contributions to nephrology
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Over last half century, the concept of acute renal failure has evolved and with it our estimates of the incidence, prevalence and mortality. Indeed, until very recently no standard definition of acute renal failure was available, and this lack of a common language created confusion and made comparisons all but impossible. In response to the need for a common definition and classification of acute renal failure, the Acute Dialysis Quality Initiative group of experts developed and published a set of consensus criteria for defining and classifying acute renal failure. ⋯ Renal dysfunction was no longer only considered significant when it reached the stage of failure, but a spectrum from early risk to long-term failure was recognized and codified. Subsequent studies have validated these criteria in various populations and have shown that relatively mild dysfunction is associated with adverse outcomes. The term acute kidney injury has subsequently been proposed to distinguish this new concept from the older terminology of failure.
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The pathogenesis of acute kidney injury (AKI) is complex and varies to some extent based on the particular cause. Inflammation contributes to this pathophysiology in a variety of contexts. Inflammation can result in reduction in local blood flow to the outer medulla with adverse consequences on tubule function and viability. ⋯ In collaboration with Serhan et al. we recently reported that, in response to bilateral ischemia/reperfusion injury, mouse kidneys produce D series resolvins (RvDs) and PD1 [J Immunol 2006;177:5902-5911]. Administration of RvDs or PD1 to mice prior to, or subsequent to, ischemia resulted in a reduction in functional and morphological kidney injury. Understanding how these anti-inflammatory processes are regulated may provide insight into how we might intervene to facilitate and enhance them so that we might prevent or mitigate the devastating consequences of AKI.
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From the recent past, hemofiltration, particularly high-volume hemofiltration, has rapidly evolved from a somewhat experimental treatment to a potentially effective 'adjunctive' therapy in severe septic shock and especially refractory or catecholamine-resistant hypodynamic septic shock. Nonetheless, this approach lacks prospective randomized studies (PRTs) evaluating the critical role of early hemofiltration in sepsis. An important milestone, which could be called the 'big bang' in terms of hemofiltration, was the publication of a PRT in patients with acute renal failure (ARF). ⋯ This could be called the big bang of hemofiltration as one could have never anticipated that an adequate dose of hemofiltration could markedly influence the survival rate of septic ARF patients in the ICU. Apart from the use of an early and adequate dose of Honoré/Joannes-Boyau/Gressens 372 hemofiltration in sepsis, a higher dose could also provide a better renal recovery rate and reduce the risk of associate chronic dialysis in these patients. Furthermore, this presentation will also review brand-new papers regarding the use of hemofiltration in systemic inflammatory response syndrome and out-of-hospital cardiac arrest.
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A change in serum creatinine is the standard metric used to define and monitor the progression of acute kidney injury (AKI). This marker is inadequate for a number of reasons including the fact that changes in serum creatinine are delayed in time after kidney injury and hence creatinine is not a good indicator to use in order to target therapy in a timely fashion. There is an urgent need for early biomarkers for the diagnosis of AKI. ⋯ In this article the status of 5 potential urinary biomarkers for AKI are discussed: kidney injury molecule-1, N-acetyl-Beta-D-glucosaminidase, neutrophil gelatinase-associated lipocalin, cystatin C, and interleukin-18. Considerable progress has been made although much continues to be needed to validate these markers for routine clinical use. Armed with these new tools the future will look much brighter for the patient with AKI as it is likely that early diagnosis and better predictors of outcome will lead to new therapies which can be introduced earlier in the course of disease.
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A reliable biomarker as an indicator of the presence of severe sepsis is an unmet medical need. ⋯ Despite their shortcomings, a number of existing and candidate biomarker assays are available and can provide some useful information to the clinician caring for septic patients. The relative merits of endotoxin measurement, interleukin-6 levels and a variety of other sepsis markers are reviewed. Full implementation of these biomarkers may improve diagnostic accuracy over the standard clinical criteria for sepsis.