CiteULike: jyuh Bagshaw

Conventional markers of kidney function.

SM Bagshaw — 2008-05-07T09:26:47-00:00

Critical care medicine, Vol. 36, No. 4 Suppl. (April 2008)

Acute kidney injury remains a serious clinical problem for intensive care unit patients, and its incidence is rising. The detection and diagnosis of acute kidney injury in the intensive care unit currently require use of conventional markers of kidney function, specifically, serum creatinine and urea levels and, less frequently, other urinary tests. These conventional markers are familiar to clinicians and have long been used at the bedside. However, these markers are clearly not ideal, each has limitations, and none reflect real-time changes in glomerular filtration rate or a genuine acute injurious process to the kidney. More importantly, these conventional markers can contribute to delays in recognition of acute kidney injury and, hence, delays to appropriate supportive and therapeutic interventions. The early detection and diagnosis of acute kidney injury should be a clinical priority. A diagnostic test or panel of tests that are capable of evaluating aspects both of kidney function and acute injury are desperately needed in critical care nephrology. Cystatin C has been shown superior to conventional markers and may assume a greater role in intensive care unit patients for detecting both early changes in glomerular filtration rate and evidence of acute injury. Other newly characterized markers of kidney function or acute injury have the potential to revolutionized the field of critical care nephrology and greatly improve the supportive and therapeutic management of intensive care unit patients with acute kidney injury.

Outcome comparisons of intermittent and continuous therapies in acute kidney injury: What do they mean?

C Ronco — 2008-05-05T02:53:53-00:00

The International journal of artificial organs, Vol. 31, No. 3. (March 2008), pp. 213-220.

Despite the fact that no new clinical outcome studies comparing intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) have been published in the past year, two meta-analyses addressing the topic (Bagshaw et al, Crit Care Med 2008; 36: 610-7, and Pannu et al, JAMA 2008; 299: 793-805) have been published recently. With respect to randomized controlled trials (RCTs), there was a substantial overlap between the studies considered in the analysis by Bagshaw et al and those considered in the analysis by Pannu et al. Although neither metaanalysis showed a benefit for either modality with respect to mortality or renal recovery, the two publications offered vastly different conclusions. Bagshaw et al concluded it is impossible to make any definitive recommendations about dialysis modality choice in AKI because previous studies were not adequately powered and failed to standardize for treatment dose. On the other hand, because the metaanalysis of Pannu et al demonstrated equivalent patient outcomes, and in light of the lower costs of IHD, they suggested that alternate-day hemodialysis should become the preferred therapy in many critically ill patients. As the clinical practice recommendations made by Pannu and colleagues have very important implications, we believe their analysis should be critically assessed. In this review, the weaknesses of the RCTs considered in the meta-analysis by Pannu et al are presented. Furthermore, the assumption by Pannu et al that IHD is associated with lower costs than CRRT is challenged, as they did not consider adequately both the short-term and long-term costs associated with the dialytic management of AKI patients. Based on our critical analysis, we believe the AKI dialytic treatment approach recommended by the JAMA investigators (Pannu et al) is not supported by the aggregate of the available clinical outcome data and, therefore, remains highly controversial. We would like to join with others in the AKI field by strongly recommending that investigators and other clinicians stop trying to make conclusive determinations about dialysis modalities when robust supportive data simply are not available. Instead of additional intermodality comparisons, the focus of future clinical research should be toward generating high-quality data on intramodality interventions, such as treatment dose and timing of treatment initiation. In this regard, at least for CRRT, we anxiously await the results of the ongoing RCTs evaluating the effect of CRRT dose on patient outcome.

Continuous versus intermittent renal replacement therapy for critically ill patients with acute kidney injury: a meta-analysis.

SM Bagshaw — 2008-05-05T02:49:10-00:00

Critical care medicine, Vol. 36, No. 2. (February 2008), pp. 610-617.

OBJECTIVE: To appraise the literature on the effect of initial renal replacement therapy (RRT) modality on clinical outcomes. DESIGN: Systematic review and meta-analysis. SETTING: Academic medical center. PATIENTS AND PARTICIPANTS: Adult critically ill patients with acute kidney injury. INTERVENTIONS: Continuous vs. intermittent RRT. MEASUREMENTS AND RESULTS: MEDLINE, EMBASE, Cochrane Controlled Clinical Trials Register, and other sources were searched. We identified nine unique randomized trials (n = 1,403). No trial satisfied all quality indicators and several had limitations related to selection bias, randomization, imbalances in patient characteristics, and high treatment crossover. No trial standardized the timing, criteria, for initiation or dose of RRT. There was no statistical evidence that initial modality influenced mortality (odds ratio, 0.99; 95% confidence interval, 0.78-1.26, p = .93; I2 = 11%; nine trials, n = 1,403) or recovery to RRT independence (odds ratio, 0.76; 95% confidence interval, 0.28-2.07, p = .59; I2 = 0%; four trials, n = 306). There was suggestion that continuous RRT had fewer episodes of hemodynamic instability and better control of fluid balance. CONCLUSIONS: We identified numerous issues related to study design, conduct, and quality that dispute the validity and question any inferences that can be drawn from these trials. In the context of these limitations, the initial RRT modality did not seem to affect mortality or recovery to RRT independence. There is urgent need for additional high-quality and suitably powered trials to adequately address this issue.

Urinary biomarkers in septic acute kidney injury

Bagshaw — 2007-08-29T21:07:07-00:00

Intensive Care Medicine, Vol. 33, No. 7. (July 2007), pp. 1285-1296.

Loop diuretics in the management of acute renal failure: a systematic review and meta-analysis.

SM Bagshaw — 2007-09-04T08:23:08-00:00

Crit Care Resusc, Vol. 9, No. 1. (March 2007), pp. 60-68.

BACKGROUND: Loop diuretics are commonly used in critically ill patients with acute renal failure (ARF), but their effect on clinical outcome remains uncertain. We systematically reviewed the literature comparing loop diuretics with control in the management of ARF. METHODS: Studies were identified by search of MEDLINE, EMBASE, and the Cochrane Controlled Clinical Trials Register, and review of proceedings from selected scientific meetings and clinical trial registries, and bibliographies of retrieved citations. We selected randomised controlled trials (RCTs) comparing loop diuretics with control in patients with ARF. Data were extracted in duplicate by two independent reviewers on study characteristics, quality and outcomes. Primary outcomes were mortality, need for renal replacement therapy (RRT) and renal recovery. Secondary outcomes were change to urine output, serum potassium level and acid-base status, duration of ARF or RRT, length of hospital stay and toxicity. RESULTS: Of 62 studies reviewed, five RCTs, enrolling 555 patients, were eligible and analysed. These trials enrolled a mix of patients, but only two included critically ill patients. Overall trial quality was low. There was no statistical difference in mortality (odds ratio [OR], 1.28; 95% CI, 0.89-1.84; P=0.18) or renal recovery (OR, 0.88; 95% CI, 0.59-1.31; P=0.5) with use of loop diuretics compared with control. However, loop diuretics were associated with a shorter duration of RRT (weighted mean difference, ?1.4 days; 95% CI, ?0.2 to ?2.3 days; P=0.02), shorter time to spontaneous decline in serum creatinine level (weighted mean difference, ?2.1 days; 95% CI, ?0.4 to ?3.7 days; P=0.01) and a greater increase in urine output from baseline (OR, 2.6; 95% CI, 1.4-4.9; P=0.004). Insufficient data were available on acid-base status, hospital length of stay or health costs. Four studies reported toxicity, most commonly transient tinnitus and deafness. CONCLUSIONS: Loop diuretics were not associated with improved mortality or rate of independence from RRT, but were associated with shorter duration of RRT and increased urine output. However, these findings have limited relevance to critically ill patients. The relative paucity of high-quality data assessing the value of loop diuretics in ARF for the critically ill suggests a need for a suitably powered randomised trial.

Acetylcysteine in the prevention of contrast-induced nephropathy: a case study of the pitfalls in the evolution of evidence.

SM Bagshaw — 2007-09-04T08:20:44-00:00

Arch Intern Med, Vol. 166, No. 2. (23 January 2006), pp. 161-166.

During the past 5 years, 19 randomized controlled trials, 4 prospective nonrandomized studies, and 11 meta-analyses that explored the role of acetylcysteine for prevention of contrast-induced nephropathy have been published. Herein, we summarize this literature and demonstrate that these 34 empirical studies have not yet conclusively resolved this research question. We use the evidence on acetylcysteine as a case study of how research evidence accumulates and consider whether an alternative approach to investigating the question of acetylcysteine's efficacy could have resulted in a more definitive conclusion. We consider the broader lessons learned from this acetylcysteine case study for the medical and research communities and propose specific steps that could be taken to improve the future coordination of research activity to ultimately yield more meaningful and definitive evidence on important clinical questions.

Septic Acute Kidney Injury in Critically Ill Patients: Clinical Characteristics and Outcomes

Sean Bagshaw — 2007-07-15T14:45:06-00:00

Clin J Am Soc Nephrol, Vol. 2, No. 3. (1 May 2007), pp. 431-439.

Sepsis is the most common cause of acute kidney injury (AKI) in critical illness, but there is limited information on septic AKI. A prospective, observational study of critically ill patients with septic and nonseptic AKI was performed from September 2000 to December 2001 at 54 hospitals in 23 countries. A total of 1753 patients were enrolled. Sepsis was considered the cause in 833 (47.5%); the predominant sources of sepsis were chest and abdominal (54.3%). Septic AKI was associated with greater aberrations in hemodynamics and laboratory parameters, greater severity of illness, and higher need for mechanical ventilation and vasoactive therapy. There was no difference in enrollment kidney function or in the proportion who received renal replacement therapy (RRT; 72 versus 71%; P = 0.83). Oliguria was more common in septic AKI (67 versus 57%; P < 0.001). Septic AKI had a higher in-hospital case-fatality rate compared with nonseptic AKI (70.2 versus 51.8%; P < 0.001). After adjustment for covariates, septic AKI remained associated with higher odds for death (1.48; 95% confidence interval 1.17 to 1.89; P = 0.001). Median (IQR) duration of hospital stay for survivors (37 [19 to 59] versus 21 [12 to 42] d; P < 0.0001) was longer for septic AKI. There was a trend to lower serum creatinine (106 [73 to 158] versus 121 [88 to 184] micromol/L; P = 0.01) and RRT dependence (9 versus 14%; P = 0.052) at hospital discharge for septic AKI. Patients with septic AKI were sicker and had a higher burden of illness and greater abnormalities in acute physiology. Patients with septic AKI had an increased risk for death and longer duration of hospitalization yet showed trends toward greater renal recovery and independence from RRT. 10.2215/CJN.03681106