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John A Kellum

Publications and source records attributed to John A Kellum.

At least 19 recordsLinked to original sources
PubMed2007

Prevention of acute renal failure.

Acute renal failure (ARF) comprises a family of syndromes that is characterized by an abrupt and sustained decrease in the glomerular filtration rate. In the ICU, ARF is most often due to sepsis and other systemic inflammatory states. ARF is common among the critically ill and injured and significantly adds to morbidity and mortality of these patients. Despite many advances in medical technology, the mortality and morbidity of ARF in the ICU continue to remain high and have not improved significantly over the past 2 decades. Primary strategies to prevent ARF still include adequate hydration, maintenance of mean arterial pressure, and minimizing nephrotoxin exposure. Diuretics and dopamine have been shown to be ineffective in the prevention of ARF or improving outcomes once ARF occurs. Increasing insight into mechanisms leading to ARF and the importance of facilitating renal recovery has prompted investigators to evaluate the role of newer therapeutic agents in the prevention of ARF.

Acetylcysteine↗
PubMed2006

Defining and classifying acute renal failure: from advocacy to consensus and validation of the RIFLE criteria.

Until recently, more than 30 different definitions of acute renal failure (ARF) had been used in the literature. This lack of a common reference point created confusion and made comparisons difficult. It also led to strong advocacy of a consensus definition. In response to the need for a common definition and classification of ARF, the Acute Dialysis Quality Initiative (ADQI) group of experts developed and published a consensus definition of ARF. This definition goes under the acronym of RIFLE to indicate that it classifies patients with renal dysfunction according to the degree of impairment into patients at risk (R), with injury (I), with failure (F), with sustained loss (L) and with end-stage (E) status in relation to their renal function. This editorial aims to summarize and interpret recent findings concerning the application of the RIFLE criteria to the assessment of the epidemiology and the prediction of the outcome of ARF.

Acute Kidney Injury↗
PubMed2006

RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis.

INTRODUCTION: The lack of a standard definition for acute kidney injury has resulted in a large variation in the reported incidence and associated mortality. RIFLE, a newly developed international consensus classification for acute kidney injury, defines three grades of severity--risk (class R), injury (class I) and failure (class F)--but has not yet been evaluated in a clinical series. METHODS: We performed a retrospective cohort study, in seven intensive care units in a single tertiary care academic center, on 5,383 patients admitted during a one year period (1 July 2000-30 June 2001). RESULTS: Acute kidney injury occurred in 67% of intensive care unit admissions, with maximum RIFLE class R, class I and class F in 12%, 27% and 28%, respectively. Of the 1,510 patients (28%) that reached a level of risk, 840 (56%) progressed. Patients with maximum RIFLE class R, class I and class F had hospital mortality rates of 8.8%, 11.4% and 26.3%, respectively, compared with 5.5% for patients without acute kidney injury. Additionally, acute kidney injury (hazard ratio, 1.7; 95% confidence interval, 1.28-2.13; P < 0.001) and maximum RIFLE class I (hazard ratio, 1.4; 95% confidence interval, 1.02-1.88; P = 0.037) and class F (hazard ratio, 2.7; 95% confidence interval, 2.03-3.55; P < 0.001) were associated with hospital mortality after adjusting for multiple covariates. CONCLUSION: In this general intensive care unit population, acute kidney 'risk, injury, failure', as defined by the newly developed RIFLE classification, is associated with increased hospital mortality and resource use. Patients with RIFLE class R are indeed at high risk of progression to class I or class F. Patients with RIFLE class I or class F incur a significantly increased length of stay and an increased risk of inhospital mortality compared with those who do not progress past class R or those who never develop acute kidney injury, even after adjusting for baseline severity of illness, case mix, race, gender and age.

Acute Kidney Injury↗
PubMed2006

Acute kidney injury: epidemiology and diagnostic criteria.

PURPOSE OF REVIEW: To review recent advances in the definitions and diagnostic criteria for acute renal failure and acute kidney injury. To explore how these changes impact the epidemiology and clinical implications for patients in the intensive care unit. RECENT FINDINGS: Recently published consensus criteria for the definition of acute renal failure/acute kidney injury have led to significant changes in how we think about this disorder. Studies from around the world, both in and out of the intensive care unit, have shown a dramatic incidence of acute kidney injury and high associated mortality. This review considers these new findings and their historical context, and attempts to shed new light on this old problem. SUMMARY: Small changes in kidney function in hospitalized patients are important and impact on outcome. RIFLE criteria provide a uniform definition of acute kidney injury and are increasingly used in literature.

Acute Kidney Injury↗
PubMed2006

Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients.

INTRODUCTION: Acid-base abnormalities are common in the intensive care unit (ICU). Differences in outcome exist between respiratory and metabolic acidosis in similar pH ranges. Some forms of metabolic acidosis (for example, lactate) seem to have worse outcomes than others (for example, chloride). The relative incidence of each type of disorder is unknown. We therefore designed this study to determine the nature and clinical significance of metabolic acidosis in critically ill patients. METHODS: An observational, cohort study of critically ill patients was performed in a tertiary care hospital. Critically ill patients were selected on the clinical suspicion of the presence of lactic acidosis. The inpatient mortality of the entire group was 14%, with a length of stay in hospital of 12 days and a length of stay in the ICU of 5.8 days. RESULTS: We reviewed records of 9,799 patients admitted to the ICUs at our institution between 1 January 2001 and 30 June 2002. We selected a cohort in which clinicians caring for patients ordered a measurement of arterial lactate level. We excluded patients in which any necessary variable required to characterize an acid-base disorder was absent. A total of 851 patients (9% of ICU admissions) met our criteria. Of these, 548 patients (64%) had a metabolic acidosis (standard base excess < -2 mEq/l) and these patients had a 45% mortality, compared with 25% for those with no metabolic acidosis (p < 0.001). We then subclassified metabolic acidosis cases on the basis of the predominant anion present (lactate, chloride, or all other anions). The mortality rate was highest for lactic acidosis (56%); for strong ion gap (SIG) acidosis it was 39% and for hyperchloremic acidosis 29% (p < 0.001). A stepwise logistic regression model identified serum lactate, SIG, phosphate, and age as independent predictors of mortality. CONCLUSION: In critically ill patients in which a measurement of lactate level was ordered, lactate and SIG were strong independent predictors of mortality when they were the major source of metabolic acidosis. Overall, patients with metabolic acidosis were nearly twice as likely to die as patients without metabolic acidosis.

Acidosis↗
PubMed2006

Severe sepsis in community-acquired pneumonia: when does it happen, and do systemic inflammatory response syndrome criteria help predict course?

STUDY OBJECTIVES: Most natural history studies of severe sepsis are limited to ICU populations. We describe the onset and timing of severe sepsis during the hospital course for patients hospitalized with community-acquired pneumonia (CAP). We also determine the ability of the systemic inflammatory response syndrome (SIRS) and other proposed risk stratification scores measured at emergency department (ED) presentation to predict progression to severe sepsis, septic shock, or death. DESIGN: Retrospective analysis of a prospective observational outcome study from the Pneumonia Patient Outcomes Research Team (PORT). SETTING: Four academic medical centers in the United States and Canada between October 1991 and March 1994. PARTICIPANTS: The 1,339 patients hospitalized for CAP in the PORT study cohort, and a random subset of 686 patients for whom we had information for SIRS criteria. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: All subjects had infection (CAP). Severe sepsis was defined as new-onset acute organ dysfunction in this cohort, using consensus criteria. Severe sepsis developed in one half of the patients (n = 639, 48%), nonpulmonary organ dysfunction developed in 520 patients (39%), and septic shock developed in 61 subjects (4.5%). Severe sepsis and septic shock were present at ED presentation in 457 patients (71% of severe sepsis cases) and 27 patients (44% of septic shock cases), respectively. While SIRS was common at presentation (82% of the subset of 686 had two SIRS criteria), it was not associated with increased odds for progression to severe sepsis (odds ratios [ORs], 0.65 and 0.89 for two or more SIRS criteria and three or more SIRS criteria, respectively), septic shock (ORs, 0.80 and 0.55), or death (ORs, 0.65 and 0.39), with poor discrimination (all receiver operating characteristic [ROC] areas under the curve < 0.5). The pneumonia severity index was associated with severe sepsis (p < 0.001) with moderate discrimination (ROC, 0.63). CONCLUSIONS: Severe sepsis is common in hospitalized CAP patients, occurring early in the hospital course. SIRS criteria do not appear to be useful predictors for progression to severe sepsis in CAP.

Cohort Studies↗
PubMed2006

Hyperchloremic acidosis increases circulating inflammatory molecules in experimental sepsis.

RATIONALE: Hyperchloremic acidosis is common in the critically ill and is often iatrogenic. We have previously shown that hyperchloremic acidosis increases nuclear factor-kappaB DNA binding in lipopolysaccharide-stimulated RAW 264.7 cells. However, evidence that hyperchloremic acidosis leads to increased inflammation in vivo has been limited to nitric oxide. OBJECTIVES: To determine if acidosis, induced by dilute hydrochloric acid (HCl) infusion, will increase circulating inflammatory mediator levels in an experimental model of severe sepsis in rats. METHODS: Eighteen hours after inducing lethal sepsis by cecal ligation and puncture in 20 adult, male, Sprague-Dawley rats, we randomized animals into three groups. In groups 2 and 3, we began an IV infusion of 0.1 N HCl to reduce the standard base excess (SBE) by 5 to 10 mEq/L and 10 to 15 mEq/L, respectively. In group 1, we infused a similar volume of lactated Ringer solution. In all groups infusion continued 8 h or until the animal died. MEASUREMENTS AND MAIN RESULTS: We measured arterial blood gases, whole-blood lactate, and chloride, tumor necrosis factor (TNF), interleukin (IL)-6, and IL-10 levels at 0 h, 4 h, and 8 h. All measured cytokines increased over time. Compared to group 1, animals in groups 2 and 3 exhibited greater increase in all three cytokines, with the greatest increases seen with severe acidosis. CONCLUSION: Moderate (SBE, - 5 to - 10) and severe (SBE, - 10 to - 15) acidosis, induced by HCl infusion, increases circulating levels of IL-6, IL-10, and TNF in normotensive septic rats.

Acid-Base Equilibrium↗
PubMed2005

The phase 2 enzyme inducers ethacrynic acid, DL-sulforaphane, and oltipraz inhibit lipopolysaccharide-induced high-mobility group box 1 secretion by RAW 264.7 cells.

The diuretic ethacrynic acid (EA) has been shown to inhibit signaling by the proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB). Accordingly, we sought to determine whether this compound is capable of inhibiting the release of cytokines [interleukin (IL)-6 and IL-10] and NO from RAW 264.7 murine macrophage-like cells stimulated with lipopolysaccharide (LPS). Additionally, we sought to determine whether EA can inhibit secretion of high-mobility group box 1 (HMGB1), a nuclear protein that is secreted by immunostimulated macrophages and functions in the extracellular milieu as a proinflammatory mediator. In a concentration-dependent manner, EA inhibited secretion of IL-6, IL-10, nitric oxide, and HMGB1. As expected, EA inhibited NF-kappaB DNA binding in LPS-stimulated RAW 264.7 cells. Treating these cells with pyrrolidine dithiocarbamate, SN50 (amino acid sequence AAVALLPAVLLALLAPVQRKRQKLMP) or 5-(thien-3-yl)-3-aminothiophene-2-carboxamide (SC-514) also inhibited LPS-induced NF-kappaB DNA binding, but these compounds failed to inhibit LPS-induced HMGB1 secretion. These findings suggested that inhibition of HMGB1 secretion by EA might occur via a mechanism unrelated to the NF-kappaB signaling pathway. Because EA is an electrophilic compound that is known to be capable of inducing expression of so-called phase 2 proteins, we sought to determine whether two other phase 2 enzyme inducers, oltipraz and DL-sulforaphane, also are capable of inhibiting HMGB1 release from immunostimulated macrophages. Incubating RAW 264.7 cells with either oltipraz or DL-sulforaphane inhibited LPS-induced HMGB1 secretion. Moreover, both EA and DL-sulforaphane inhibited relocalization of nuclear HMGB1 into the cytoplasm of LPS-stimulated RAW 264.7 cells. These data suggest that phase 2 inducers may exert anti-inflammatory effects by inhibiting secretion of the cytokine-like nuclear protein HMGB1.

Active Transport, Cell Nucleus↗
PubMed2005

Acute renal failure in critically ill patients: a multinational, multicenter study.

CONTEXT: Although acute renal failure (ARF) is believed to be common in the setting of critical illness and is associated with a high risk of death, little is known about its epidemiology and outcome or how these vary in different regions of the world. OBJECTIVES: To determine the period prevalence of ARF in intensive care unit (ICU) patients in multiple countries; to characterize differences in etiology, illness severity, and clinical practice; and to determine the impact of these differences on patient outcomes. DESIGN, SETTING, AND PATIENTS: Prospective observational study of ICU patients who either were treated with renal replacement therapy (RRT) or fulfilled at least 1 of the predefined criteria for ARF from September 2000 to December 2001 at 54 hospitals in 23 countries. MAIN OUTCOME MEASURES: Occurrence of ARF, factors contributing to etiology, illness severity, treatment, need for renal support after hospital discharge, and hospital mortality. RESULTS: Of 29 269 critically ill patients admitted during the study period, 1738 (5.7%; 95% confidence interval [CI], 5.5%-6.0%) had ARF during their ICU stay, including 1260 who were treated with RRT. The most common contributing factor to ARF was septic shock (47.5%; 95% CI, 45.2%-49.5%). Approximately 30% of patients had preadmission renal dysfunction. Overall hospital mortality was 60.3% (95% CI, 58.0%-62.6%). Dialysis dependence at hospital discharge was 13.8% (95% CI, 11.2%-16.3%) for survivors. Independent risk factors for hospital mortality included use of vasopressors (odds ratio [OR], 1.95; 95% CI, 1.50-2.55; P<.001), mechanical ventilation (OR, 2.11; 95% CI, 1.58-2.82; P<.001), septic shock (OR, 1.36; 95% CI, 1.03-1.79; P = .03), cardiogenic shock (OR, 1.41; 95% CI, 1.05-1.90; P = .02), and hepatorenal syndrome (OR, 1.87; 95% CI, 1.07-3.28; P = .03). CONCLUSION: In this multinational study, the period prevalence of ARF requiring RRT in the ICU was between 5% and 6% and was associated with a high hospital mortality rate.

Acute Kidney Injury↗
PubMed2005

Clinical review: reunification of acid-base physiology.

Recent advances in acid-base physiology and in the epidemiology of acid-base disorders have refined our understanding of the basic control mechanisms that determine blood pH in health and disease. These refinements have also brought parity between the newer, quantitative and older, descriptive approaches to acid-base physiology. This review explores how the new and older approaches to acid-base physiology can be reconciled and combined to result in a powerful bedside tool. A case based tutorial is also provided.

Acid-Base Equilibrium↗
PubMed2005

Determinants of plasma acid-base balance.

An advanced understanding of acid-base physiology is central to the practice of critical care medicine. Intensivists spend much of their time managing problems that are related to fluids, electrolytes, and blood pH. Recent advances in the understanding of acid-base physiology occurred as the result of the application of basic physical-chemical principles of aqueous solutions to blood plasma. This analysis revealed three independent variables that regulate pH in blood plasma: carbon dioxide, relative electrolyte concentrations, and total weak acid concentrations. All changes in blood pH, in health and in disease, occur through changes in these three variables. This article reviews the physical-chemical approach to acid-base balance and considers clinical implications for these findings.

Acid-Base Equilibrium↗
PubMed2005

Adequacy of dialysis in acute renal failure.

Renal replacement therapy (RRT) is currently the mainstay of management for patients with acute renal failure (ARF). Adequacy of dialysis in the setting of renal failure is defined poorly and encompasses multiple domains of clinical and biochemical outcomes. Multiple operational factors influence the delivery of adequate dialysis. No current standards exist for RRT for ARF; current RRT practices for ARF generally have been extrapolated from end-stage renal disease (ESRD) literature. The heterogeneity of patient population, variation in RRT practices, and differences in outcomes studied have made it difficult to define or study adequate dialysis in ARF or its impact on clinical outcomes.

Acute Kidney Injury↗
PubMed2005

Acute renal failure in the critically ill.

PURPOSE OF REVIEW: Acute renal failure occurs frequently in hospitalized patients and is associated with significant morbidity and mortality. An effort to better understand the epidemiology and pathophysiology of this disease will hopefully lead to improvement in patient outcomes. Considerable effort has been expended to develop techniques to prevent acute renal failure or to facilitate its resolution. In this review we attempt to summarize some of these recent advances. RECENT FINDINGS: Attempts have been made to clearly define acute renal failure. Among the available pharmacologic agents, current evidence suggests that with the possible exception of radio-contrast-induced acute renal failure, no drugs are capable of preventing the condition or hastening its recovery. Advances in techniques and understanding of how to best provide renal replacement therapy appear to have improved patient outcomes and several newer treatments are under preclinical evaluation and may hold promise for the future. SUMMARY: Preventing acute renal failure, improving clinical outcomes of the condition and attempts to hasten renal recovery have all been very attractive but difficult propositions. Recent efforts to explore the underlying pathophysiology and insight into mechanisms leading to acute renal failure have triggered investigators to evaluate novel therapeutic agents and enhance existing dialytic techniques. These hold great promise for improving patient outcomes in the near future.

Journal Article↗
PubMed2005

External validation of severity scoring systems for acute renal failure using a multinational database.

OBJECTIVE: Several different severity scoring systems specific to acute renal failure have been proposed. However, most validation studies of these scoring systems were conducted in a single center or in a small number of centers, often the same ones used for their development. Therefore, it is not known whether such severity scoring systems may be widely applied. DESIGN: Prospective clinical investigation. SETTING: Intensive care units. PATIENTS: One thousand seven hundred and forty-two intensive care unit patients with acute renal failure who were either treated with renal replacement therapy or fulfilled predefined criteria. INTERVENTIONS: Demographic and clinical information and outcomes were measured. MEASUREMENTS AND MAIN RESULTS: Scores for four acute renal failure-specific scoring systems and two general scoring systems (Simplified Acute Physiology Score II and Sequential Organ Failure Assessment) were calculated, and their discrimination and calibration were tested with receiver operating characteristic curves and Hosmer-Lemeshow goodness-of fit-tests. For the receiver operating characteristic curves, blood lactate levels were also used as a reference. All scores had an area under the receiver operating characteristic curve <0.7 (Mehta 0.670, Liano 0.698, Chertow 0.610, Paganini 0.643, Simplified Acute Physiology Score II 0.645, Sequential Organ Failure Assessment 0.675, lactate 0.639). For scores that can calculate predicted mortality, the Hosmer-Lemeshow goodness-of-fit test showed poor calibration. CONCLUSIONS: None of the scoring systems tested had a high level of discrimination or calibration to predict mortality for patients with acute renal failure when tested in a broad cohort of patients from multiple countries. A large, multiple-center database might be needed to improve the discrimination and calibration of acute renal failure scoring system.

Acute Kidney Injury↗
PubMed2005

Interleukin-6.

Explore the source record for details and available documents.

Animals↗
PubMed2005

Primary prevention of acute renal failure in the critically ill.

PURPOSE OF REVIEW: Acute renal failure is both common and highly lethal in the intensive care unit, with hospital mortality rates in excess of 50%. To date, no therapy apart from renal replacement therapy has been shown to improve survival or enhance recover. Thus, efforts to prevent acute renal failure are eagerly sought. RECENT FINDINGS: Fluids and avoiding hypotension and nephrotoxins appear to be the most effective strategies to prevent acute renal failure. N-acetylcysteine has been shown to prevent the increase in serum creatinine in high risk patients given intravenous radiocontrast agents, although there is some evidence that N-acetylcysteine may reduce serum creatinine without increasing glomerular filtration. SUMMARY: The best evidence suggests that nonpharmacologic strategies are more effective than drugs in reducing the risk of acute renal failure. Evidence also exists that strategies that improve survival in critically ill patients also reduce the incidence of organ failure, including acute renal failure.

Acute Kidney Injury↗