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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.

During acute kidney injury (AKI), lowered glomerular filtration rate (GFR) is believed to be consequent to reduced renal plasma flow (RPF). We aimed to systematically evaluate the evidence for such an association. Using specific search terms, we systematically interrogated the Pub Med electronic reference database for studies of human AKI where renal plasma or blood flow and GFR were measured; older articles were then identified by screening bibliographies of retrieved reports. We identified 22 articles describing 250 patients (203 native kidney, 47 in renal allograft). Of these studies, 8 articles (110 patients) estimated effective renal plasma flow (ERPF) by clearance techniques and 14 articles (140 patients) estimated true renal plasma flow (TRPF). Mean RPF was 272 mL/min (95% CI 213-331) and GFR 13.9 mL/min (9.9-17.9). Mean TRPF was significantly greater than mean ERPF (344 vs. 180, p=0.004) despite lower mean GFR (8.8 vs. 20.4, p=0.002). There was no significant association between RPF and GFR between studies. Eleven studies presented individual patient data (76 patients: 49 TRPF, 27 ERPF); here, individual patient ERPF was associated with GFR (r2=0.52), but TRPF was not. During AKI in man, there is only a limited association between ERPF and GFR, and no detectable association between TRPF and GFR.

There is limited information on the incidence of acute kidney injury (AKI) in patients with traumatic brain injury (TBI) although AKI may contribute to morbidity and mortality. We investigated the incidence of AKI in patients with moderate and severe TBI and the association of AKI with risk factors and outcomes in these patients. We studied all TBI patients over 16 years of age admitted to the two designated trauma hospitals in the state of Victoria, Australia from 1 January to 31 December 2008. Patients were included if they had head trauma and presented with a Glasgow coma scale (GCS) <13. Prospectively collected data from the hospital trauma registries, ICUs, and pathology databases were analyzed retrospectively. Risk injury failure loss end (RIFLE) criteria were used to categorize renal function. The incidence of AKI was 9.2% (19/207). Patients who developed AKI were older, had higher severity of illness scores, and a lower GCS. Overall 42.1% of these patients died in hospital compared with 18.1% in patients without AKI. In univariable linear regression analysis, age, severity of illness, and admitting hospital were associated with AKI. After multivariable logistic regression, the occurrence of AKI was associated with age (p < 0.001) and higher APACHE III scores (p = 0.016). AKI is relatively common even in patients with TBI. Its association with age and APACHE III scores helps identify patients at higher risk of AKI.

Rationale: Few studies have evaluated the epidemiology of acute kidney injury (AKI) in trauma., Objective: To evaluate the incidence, risk factors, and outcomes associated with early AKI (evident within 24 hours of admission) in critically ill trauma patients., Methods: A retrospective interrogation of prospectively collected data from the Australian New Zealand Intensive Care Society Adult Patient Database. A total of 9,449 trauma patients were admitted for >or=24 hours to 57 intensive care units across Australia from January 1(st), 2000, to December 31(st), 2005., Main Findings: The crude incidence of AKI was 18.1% (n = 1,711). Older age, female sex (OR 1.60, 95% CI, 1.43-1.78, p < 0.0001), and the presence of co-morbid illness (OR 2.70, 95% CI 2.3-3.2, p < 0.0001) were associated with higher odds of AKI. Those with trauma not associated with brain injury (OR 2.40, 95% CI, 2.1-2.7, p < 0.0001) and a higher illness severity (OR 1.12, 95% CI, 1.11-1.12, p < 0.001) also had higher likelihood of AKI. Overall, AKI was associated with a higher crude mortality (16.7% vs. 7.8%, OR 2.36, 95% CI, 2.0-2.7, p < 0.001). Each RIFLE category of AKI was independently associated with hospital mortality in multi-variable analysis (risk: OR 1.69; injury OR 1.88; failure 2.29)., Conclusions: Trauma admissions to ICU are frequently complicated by early AKI. Those at high risk for AKI appear to be older, female, with co-morbid illnesses, and present with greater illness severity. Early AKI in trauma is also independently associated with higher mortality. These data indicate a higher burden of AKI than previously described.

Objective: To compare the effect of lactate vs. bicarbonate-buffered replacement fluids on electrolyte mass balance during isovolemic continuous veno-venous hemofiltration (CVVH)., Design: Randomized controlled study with double cross over., Setting: Intensive care unit of a tertiary university hospital., Patients and Participants: Eight patients with acute renal failure (ARF)., Interventions: Isovolemic CVVH (2L/hr of replacement fluid) was performed in random order with either bicarbonate or lactate-buffered replacement fluid delivered pre-filter., Measurements and Results: Sodium, potassium, chloride, magnesium, and phosphate, were measured in each sample. There was a mass gain of sodium, which was similar under both conditions (bicarbonate: 23.3+/-4.9 mmol/hr, lactate: 22.7+/-3.5 mmol/hr). Mass chloride gains occurred with bicarbonate-buffered replacement fluid only (12.8+/-5.3 mmol/hr), while there was an overall net loss of chloride with lactate fluids (-2.5+/-5.2 mmol/hr), resulting in a significant difference in chloride mass balance (p<0.0001). Magnesium mass balance was negative with bicarbonate buffer only (-0.6+/-0.2 mmol/hr) and also differed significantly from that obtained with lactate fluids (-0.1+/-0.2 mmol/hr, p<0.0001). Phosphate losses (bicarbonate: -1.7+/-0.7 mmol/hr, lactate: -1.7+/-0.5 mmol/hr) were equivalent with both buffers. Potassium mass balance was neutral., Conclusions: Mass balance during isovolemic CVVH is significantly affected by the type of replacement fluid administered prefilter. Isovolemic CVVH is not isonatremic and the use of bicarbonate-buffered fluid results in a significant accumulation of chloride and a loss of magnesium.

Background and Aims: The prevention of filter clotting is an important goal in the management of continuous renal replacement therapy (CRRT). Anticoagulation is the mainstay of such prevention. However, other strategies might prolong filter life without increasing the risk of bleeding. We tested the effectiveness of three strategies (use of flat plate configuration, heparin administration into the air chamber and use of a larger membrane surface) aimed at prolonging circuit life without increasing the dose of anticoagulation., Methods: Thirty-one critically ill patients with acute renal failure (ARF) managed with continuous venovenous hemofiltration (CVVH) were studied. Filters were randomized in a crossover design to three consecutive studies: (1) filtration with either hollow-fiber or flat-plate hemofilters, (2) administration of heparin dose pre-filter or divided into pre-filter and directly into the bubble trap chamber and (3) use of two different surface areas with Filtral 8 (surface area 0.75 m2) vs. Filtral 12 (surface area 1.30 m2) hemofilters., Results: Mean circuit life for flat-plate and hollow-fiber hemofilters (cohort 1) was 14.7 +/- 4.7 h and 17.1 +/- 2.8h respectively (NS). Mean circuit life for single heparin administration site vs. double site administration (cohort 2) was 17 +/- 3.2 h and 18 +/- 3.1 h respectively (NS). Mean circuit lifespan for 0.75 m2 and 1.30 m2 hemofilters was 16 +/- 12.2 h and 15.7 +/- 14.3 h respectively (NS) (cohort 3). Visible clot formation in the bubble trap chamber was a frequent cause of circuit failure., Conclusion: Neither flat plate membrane configuration nor increasing membrane surface area, nor heparin administration in the air chamber prolong circuit life during CWH. The bubble trap chamber is a frequent site of circuit clotting.

Background and Objectives: Different techniques of continuous renal replacement therapy (CRRT) might have different effects on azotemic control. Accordingly, we tested whether continuous veno-venous hemodiafiltration (CVVHDF) or continuous veno-venous hemofiltration (CVVH) would achieve better control of serum creatinine and plasma urea levels., Design: Retrospective controlled study., Setting: Two tertiary Intensive Care Units., Patients: Critically ill patients with acute renal failure (ARF) treated with CVVHDF (n = 49) or CVVH (n = 50)., Interventions: Retrieval of daily morning urea and creatinine values before and after the initiation of CRRT for up to 2 weeks of treatment., Measurements and Results: Before treatment, serum urea and creatinine concentrations were significantly lower in the CVVH group than in CVVHDF group (urea: 31.0 +/- 15.0 mmol/L for CVVHDF and 24.7 +/- 16.1 mmol/L for CVVH, p = 0.01, creatinine: 547 +/- 308 micromol/L vs. 326 +/- 250 micromol/L, p < 0.0001). These differences were still significant after 48 h of treatment (urea: 20.1 +/- 8.3 mmol/L vs. 14.1 +/- 6.1 mmol/L; p = 0.0003, creatinine: 360 +/- 189pmol/L vs. 215 +/- 118 micromol/L; p < 0.0001). Throughout the duration of therapy, mean urea levels (22.3 +/- 9.0 mmol/L for CVVHDF vs. 16.7 +/- 7.8 mmol/L for CVVH, p < 0.0001) and mean creatinine levels (302 +/- 167 vs. 211 +/- 103 micromol/L, p < 0.0001) were better controlled in the CVVH group., Conclusions: CRRT strategies based on different techniques might have a significantly different impact on azotemic control.

Background: Achieving "adequacy of dialysis" includes the maintenance of normal serum ionized calcium concentrations and is an important therapeutic goal in the treatment of acute renal failure (ARF). It is unknown whether this goal is best achieved with intermittent or continuous renal replacement therapy., Methods: We compared the effects of continuous veno-venous hemodiafiltration (CVVHDF) and intermittent hemodialysis (IHD) on serum ionized calcium concentrations using daily morning blood tests in 88 consecutive intensive care patients of which half were treated with IHD and half with CRRT., Results: Mean patient age was 54 +/- 14 years for IHD and 60 +/- 14 years for CVVHDF (NS). However, patients who received CVVHDF were significantly more critically ill (mean APACHE II scores: 24.4 +/- 5.1 for IHD vs. 29.2 +/- 5.7 for CVVHDF, p < 0.003). Before treatment, the mean ionized calcium concentration was 1.177 +/- 0.03 mmol/l for IHD and 1.172 +/- 0.04 mmol/l for CVVHDF (NS), with abnormal values in 51.6% of IHD patients and in 68% of CVVHDF patients (NS). During treatment, hypocalcemia was significantly more common among CVVHDF patients (24.5% vs. 14.9%; p < 0.011) while hypercalcemia was more frequent during IHD (36.1% vs. 25.6%; p < 0.019)., Conclusions: Abnormal serum ionized calcium concentrations are frequent in ARF patients before and during renal replacement. Once dialytic therapy is applied, CVVHDF is more likely to lower serum calcium concentrations, while IHD is more likely to induce hypercalcemia. Appreciation of these different biochemical effects may assist clinicians in adjusting dialytic therapy in selected patients.

Objective: To test the precision and limits of agreement of point-of-care testing (POCT)-based measurement of serum creatinine (Cr) in critically ill patients. Methods: We studied 250 paired blood samples from 82 critically ill patients from a general intensive care unit by simultaneous POCT and central laboratory testing (Jaffé method). Correlation, precision, bias, and limits of agreement were assessed. Possible confounders for interference of noncreatinine chromogens were evaluated by multivariate linear regression analysis. Results: The mean difference in serum Cr measured by central laboratory and POCT was ++9.6 μmol/L (95%% limits of agreement: −11.2 to ++30.4 μmol/L). The mean percentage difference between the two techniques was 8.7%% (95%% limits of agreement −7.8%% to ++25.1%%). On multivariate regression, the difference in serum Cr was increased with greater hemoglobin and lactate levels but decreased with greater bilirubin, albumin, and calcium levels. Conclusions: Compared with the central laboratory testing, POCT-based measurement of serum Cr in critically ill patients carried a small negative bias. This difference appeared affected by the blood levels of biochemical variables known to affect the Jaffé method. POCT-based Cr measurement appears sufficiently accurate for clinical use. [ABSTRACT FROM AUTHOR]