Combination of biomarkers for diagnosis of acute kidney injury after cardiopulmonary bypass.

Novel acute kidney injury (AKI) biomarkers offer promise of earlier diagnosis and risk stratification, but have yet to find widespread clinical application. We measured urinary α and π glutathione S-transferases (α-GST and π-GST), urinary l-type fatty acid-binding protein (l-FABP), urinary neutrophil gelatinase-associated lipocalin (NGAL), urinary hepcidin and serum cystatin c (CysC) before surgery, post-operatively and at 24 h after surgery in 93 high risk patient undergoing cardiopulmonary bypass (CPB) and assessed the ability of these biomarkers alone and in combination to predict RIFLE-R defined AKI in the first 5 post-operative days. Twenty-five patients developed AKI. π-GST (ROCAUC = 0.75), lower urine Hepcidin:Creatine ratio at 24 h (0.77), greater urine NGAL:Cr ratio post-op (0.73) and greater serum CysC at 24 h (0.72) best predicted AKI. Linear combinations with significant improvement in AUC were: Hepcidin:Cr 24 h + post-operative π-GST (AUC = 0.86, p = 0.01), Hepcidin:Cr 24 h + NGAL:Cr post-op (0.84, p = 0.03) and CysC 24 h + post-operative π-GST (0.83, p = 0.03), notably these significant biomarkers combinations all involved a tubular injury and a glomerular filtration biomarker. Despite statistical significance in receiver-operator characteristic (ROC) analysis, when assessed by ability to define patients to two groups at high and low risk of AKI, combinations failed to significantly improve classification of risk compared to the best single biomarkers. In an alternative approach using Classification and Regression Tree (CART) analysis a model involving NGAL:Cr measurement post-op followed by Hepcidin:Cr at 24 h was developed which identified high, intermediate and low risk groups for AKI. Regression tree analysis has the potential produce models with greater clinical utility than single combined scores.

Greater increase in urinary hepcidin predicts protection from acute kidney injury after cardiopulmonary bypass.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication of cardiopulmonary bypass (CPB) surgery. Hepcidin, a peptide hormone that regulates iron homeostasis, is a potential biomarker of AKI following CPB. METHODS: We investigated the association between post-operative changes in serum and urinary hepcidin and AKI in 93 patients undergoing CPB. RESULTS: Twenty-five patients developed AKI based on the Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) criteria in the first 5 days. Serum hepcidin, urine hepcidin concentration, the urinary hepcidin:creatinine ratio and fractional excretion of hepcidin in urine rose significantly after surgery. However, urine hepcidin concentration and urinary hepcidin:creatinine ratio were significantly lower at 24 h in patients with RIFLE-Risk, Injury or Failure compared to those without AKI (P = 0.0009 and P < 0.0001, respectively). Receiver operator characteristic analysis showed that lower 24-h urine hepcidin concentration and urinary hepcidin:creatinine ratio were sensitive and specific predictors of AKI. The urinary hepcidin:creatinine ratio had an area under the curve for the diagnosis of RIFLE ≥ risk at 24 h of 0.77 and of 0.84 for RIFLE ≥ injury. Urinary hepcidin had similar predictive accuracy. Such predictive ability remained when patients with early creatinine increases were excluded. CONCLUSIONS: Urinary hepcidin and hepcidin:creatinine ratio are biomarkers of AKI after CPB, with an inverse association between its increase at 24 h and risk of AKI in the first five post-operative days. Measuring hepcidin in the urine on the first day following surgery may deliver earlier diagnosis and interventions.

Acquired bloodstream infection in the intensive care unit: incidence and attributable mortality.

INTRODUCTION: To estimate the incidence of intensive care unit (ICU)-acquired bloodstream infection (BSI) and its independent effect on hospital mortality. METHODS: We retrospectively studied acquisition of BSI during admissions of >72 hours to adult ICUs from two university-affiliated hospitals. We obtained demographics, illness severity and co-morbidity data from ICU databases and microbiological diagnoses from departmental electronic records. We assessed survival at hospital discharge or at 90 days if still hospitalized. RESULTS: We identified 6339 ICU admissions, 330 of which were complicated by BSI (5.2%). Median time to first positive culture was 7 days (IQR 5-12). Overall mortality was 23.5%, 41.2% in patients with BSI and 22.5% in those without. Patients who developed BSI had higher illness severity at ICU admission (median APACHE III score: 79 vs. 68, P < 0.001). After controlling for illness severity and baseline demographics by Cox proportional-hazard model, BSI remained independently associated with risk of death (hazard ratio from diagnosis 2.89; 95% confidence interval 2.41-3.46; P < 0.001). However, only 5% of the deaths in this model could be attributed to acquired-BSI, equivalent to an absolute decrease in survival of 1% of the total population. When analyzed by microbiological classification, Candida, Staphylococcus aureus and gram-negative bacilli infections were independently associated with increased risk of death. In a sub-group analysis intravascular catheter associated BSI remained associated with significant risk of death (hazard ratio 2.64; 95% confidence interval 1.44-4.83; P = 0.002). CONCLUSIONS: ICU-acquired BSI is associated with greater in-hospital mortality, but complicates only 5% of ICU admissions and its absolute effect on population mortality is limited. These findings have implications for the design and interpretation of clinical trials.

Fluid balance and acute kidney injury.

Intravenous fluids are widely administered to patients who have, or are at risk of, acute kidney injury (AKI). However, deleterious consequences of overzealous fluid therapy are increasingly being recognized. Salt and water overload can predispose to organ dysfunction, impaired wound healing and nosocomial infection, particularly in patients with AKI, in whom fluid challenges are frequent and excretion is impaired. In this Review article, we discuss how interstitial edema can further delay renal recovery and why conservative fluid strategies are now being advocated. Applying these strategies in critical illness is challenging. Although volume resuscitation is needed to restore cardiac output, it often leads to tissue edema, thereby contributing to ongoing organ dysfunction. Conservative strategies of fluid management mandate a switch towards neutral balance and then negative balance once hemodynamic stabilization is achieved. In patients with AKI, this strategy might require renal replacement therapy to be given earlier than when more-liberal fluid management is used. However, hypovolemia and renal hypoperfusion can occur in patients with AKI if excessive fluid removal is pursued with diuretics or extracorporeal therapy. Thus, accurate assessment of fluid status and careful definition of targets are needed at all stages to improve clinical outcomes. A conservative strategy of fluid management was recently tested and found to be effective in a large, randomized, controlled trial in patients with acute lung injury. Similar randomized, controlled studies in patients with AKI now seem justified.