Ongoing clinical trials in AKI

Division of Nephrology, University of Colorado and Denver Veterans Administration Medical Center, Denver, Colorado, USA.
Clinical Journal of the American Society of Nephrology (Impact Factor: 4.61). 03/2012; 7(5):861-73. DOI: 10.2215/CJN.12191111
Source: PubMed


AKI is an important public health issue. AKI is a common hospital complication associated with increased in-hospital and long-term mortality, extensive morbidity (including prolonged hospital length of stay), and an estimated annual cost of at least $10 billion in the United States. At present, no specific therapy has been developed to prevent AKI, hasten recovery of kidney function, or abrogate the deleterious systemic effects of AKI. However, recent progress includes establishing a consensus definition of AKI and discovery of novel biomarkers that may allow early detection of AKI. Furthermore, significant insights into the pathophysiology of AKI and its deleterious systemic effects have been gleaned from animal studies. Urgently needed are large, definitive randomized clinical trials testing interventions to prevent and/or treat AKI. This review summarizes and analyzes current ongoing clinical trials registered with that address prevention or management of AKI. The purpose of this review is to provide a resource for people interested in potential prophylactic and therapeutic approaches to patient care and investigators hoping to plan and execute the next round of randomized clinical trials. Finally, this review discusses research needs that are not addressed by the current clinical trials portfolio and suggests key areas for future research in AKI.

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    • "Increasing acceptance of standardized definitions of AKI amongst nephrologists and intensivists has advanced several aspects of AKI research yet the practical issue of what constitutes “true AKI” clinically, remains unsettled [3-8]. Novel biomarkers have demonstrated promising associations with AKI [3,4], leading to a resurgence in clinical trials in the setting of AKI [9]. However, given the suboptimal performance of some biomarkers, there is only limited data to support the role of accurate adjudication of AKI to improve the diagnostic and discriminative performance of traditional and modern markers of renal function [10]. "
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    ABSTRACT: Adjudication of patient outcomes is a common practice in medical research and clinical trials. However minimal data exists on the adjudication process in the setting of Acute Kidney Injury (AKI) as well as the ability to judge different etiologies (e.g. Acute Tubular Necrosis (ATN), Pre-renal Azotemia (PRA)). We enrolled 475 consecutive patients undergoing cardiac surgery at four sites of the Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) study. Three expert nephrologists performed independent chart review, utilizing clinical variables and retrospective case report forms with pre intra and post-operative data, and then adjudicated all cases of AKI (n = 67). AKI was defined as a > 50% increase in serum creatinine for baseline (RIFLE Risk). We examined the patterns of AKI diagnoses made by the adjudication panel as well as association of these diagnoses with pre and postoperative kidney injury biomarkers. There was poor agreement across the panel of reviewers with their adjudicated diagnoses being independent of each other (Fleiss’ Kappa = 0.046). Based on the agreement of the two out of three reviewers, ATN was the adjudicated diagnosis in 41 cases (61%) while PRA occurred in 13 (19%). Neither serum creatinine or any other biomarker of AKI (urine or serum), was associated with an adjudicated diagnosis of ATN within the first 24 post-operative hours. The etiology of AKI after cardiac surgery is probably multi-factorial and pure forms of AKI etiologies, such as ATN and PRA may not exist. Biomarkers did not appear to correlate with the adjudicated etiology of AKI; however the lack of agreement among the adjudicators impacted these results. Trial registration NCT00774137
    BMC Nephrology 07/2014; 15(1):105. DOI:10.1186/1471-2369-15-105 · 1.69 Impact Factor
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    • "The rapidity in which organ injury may become established after an insult has only recently been appreciated. For example, in the field of AKI, numerous therapies that showed promise in animal models failed in clinical trials [40]. However, it is now well understood that the clinical trials in patients were conducted in established disease [40]. "
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    ABSTRACT: Acute kidney injury (AKI) and acute lung injury (ALI) are serious complications of sepsis. AKI is often viewed as a late complication of sepsis. Notably, the onset of AKI relative to ALI is unclear as routine measures of kidney function (BUN and creatinine) are insensitive and increase late. In this study, we hypothesized that AKI and ALI would occur simultaneously due to a shared pathophysiology (i.e., TNF-α mediated systemic inflammatory response syndrome [SIRS]), but that sensitive markers of kidney function would be required to identify AKI. Sepsis was induced in adult male C57B/6 mice with 5 different one time doses of intraperitoneal (IP) endotoxin (LPS) (0.00001, 0.0001, 0.001, 0.01, or 0.25 mg) or cecal ligation and puncture (CLP). SIRS was assessed by serum proinflammatory cytokines (TNF-α, IL-1β, CXCL1, IL-6), ALI was assessed by lung inflammation (lung myeloperoxidase [MPO] activity), and AKI was assessed by serum creatinine, BUN, and glomerular filtration rate (GFR) (by FITC-labeled inulin clearance) at 4 hours. 20 µgs of TNF-α antibody (Ab) or vehicle were injected IP 2 hours before or 2 hours after IP LPS. Serum cytokines increased with all 5 doses of LPS; AKI and ALI were detected within 4 hours of IP LPS or CLP, using sensitive markers of GFR and lung inflammation, respectively. Notably, creatinine did not increase with any dose; BUN increased with 0.01 and 0.25 mg. Remarkably, GFR was reduced 50% in the 0.001 mg LPS dose, demonstrating that dramatic loss of kidney function can occur in sepsis without a change in BUN or creatinine. Prophylactic TNF-α Ab reduced serum cytokines, lung MPO activity, and BUN; however, post-sepsis administration had no effect. ALI and AKI occur together early in the course of sepsis and TNF-α plays a role in the early pathogenesis of both.
    PLoS ONE 11/2013; 8(11):e79037. DOI:10.1371/journal.pone.0079037 · 3.23 Impact Factor
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    ABSTRACT: Background and objectives: Incidence of AKI in hospitalized patients with cancer is increasing, but reports are scant. The objective of this study was to determine incidence rate, clinical correlates, and outcomes of AKI in patients admitted to a cancer center. Design, setting, participants, & measurements: Cross-sectional analysis of prospectively collected data on 3558 patients admitted to the University of Texas M.D. Anderson Cancer Center over 3 months in 2006. Results: Using modified RIFLE (Risk, Injury, Failure, Loss, ESRD) criteria, 12% of patients admitted to the hospital had AKI, with severity in the Risk, Injury, and Failure categories of 68%, 21%, and 11%, respectively. AKI occurred in 45% of patients during the first 2 days and in 55% thereafter. Dialysis was required in 4% of patients and nephrology consultation in 10%. In the multivariate model, the odds ratio (OR) for developing AKI was significantly higher for diabetes (OR, 1.89; 95% confidence interval [CI], 1.51-2.36), chemotherapy (OR, 1.61; 95% CI, 1.26-2.05), intravenous contrast (OR, 4.55; 95% CI, 3.51-5.89), hyponatremia (OR, 1.97; 95% CI, 1.57-2.47), and antibiotics (OR, 1.52; 95% CI, 1.15-2.02). In patients with AKI, length of stay (100%), cost (106%), and odds for mortality (4.7-fold) were significantly greater. Conclusion: The rate of AKI in patients admitted to a comprehensive cancer center was higher than the rate in most noncancer settings; was correlated significantly with diabetes, hyponatremia, intravenous contrast, chemotherapy, and antibiotics; and was associated with poorer clinical outcomes. AKI developed in many patients after admission. Studies are warranted to determine whether proactive measures may limit AKI and improve outcomes.
    Clinical Journal of the American Society of Nephrology 12/2012; 8(3). DOI:10.2215/CJN.03530412 · 4.61 Impact Factor
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