Superiority of Serum Cystatin C Over Creatinine in Prediction of Long-Term Prognosis at Discharge From ICU.

OBJECTIVES: Renal outcomes after critical illness are seldom assessed despite strong correlation between chronic kidney disease and survival. Outside hospital, renal dysfunction is more strongly associated with mortality when assessed by serum cystatin C than by creatinine. The relationship between creatinine and longer term mortality might be particularly weak in survivors of critical illness. DESIGN: Retrospective observational cohort study. PATIENTS: In 3,077 adult ICU survivors, we compared ICU discharge cystatin C and creatinine and their association with 1-year mortality. Exclusions were death within 72 hours of ICU discharge, ICU stay less than 24 hours, and end-stage renal disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During ICU admission, serum cystatin C and creatinine diverged, so that by ICU discharge, almost twice as many patients had glomerular filtration rate less than 60 mL/min/1.73 m when estimated from cystatin C compared with glomerular filtration rate estimated from creatinine, 44% versus 26%. In 743 patients without acute kidney injury, where ICU discharge renal function should reflect ongoing baseline, discharge glomerular filtration rate estimated from creatinine consistently overestimated follow-up glomerular filtration rate estimated from creatinine, whereas ICU discharge glomerular filtration rate estimated from cystatin C well matched follow-up chronic kidney disease status. By 1 year, 535 (17.4%) had died. In survival analysis adjusted for age, sex, and comorbidity, cystatin C was near-linearly associated with increased mortality, hazard ratio equals to 1.78 (95% CI, 1.46-2.18), 75th versus 25th centile. Conversely, creatinine demonstrated a J-shaped relationship with mortality, so that in the majority of patients, there was no significant association with survival, hazard ratio equals to 1.03 (0.87-1.2), 75th versus 25th centile. After adjustment for both creatinine and cystatin C levels, higher discharge creatinine was then associated with lower long-term mortality. CONCLUSIONS: In contrast to creatinine, cystatin C consistently associated with long-term mortality, identifying patients at both high and low risk, and better correlated with follow-up renal function. Conversely, lower creatinine relative to cystatin C appeared to confer adverse prognosis, confounding creatinine interpretation in isolation. Cystatin C warrants further investigation as a more meaningful measure of renal function after critical illness.

Long-term mortality and risk factors for development of end-stage renal disease in critically ill patients with and without chronic kidney disease.

INTRODUCTION: Prevalence of chronic kidney disease (CKD) amongst intensive care unit (ICU) admissions is rising. How mortality and risk of end-stage renal disease (ESRD) differs between those with and without CKD and with acute kidney injury (AKI) is unclear. Determining factors that increase the risk of ESRD is essential to optimise treatment, identify patients requiring nephrological surveillance and for quantification of dialysis provision. METHOD: This cohort study used the Swedish intensive care register 2005-2011 consisting of 130,134 adult patients. Incomplete cases were excluded (26,771). Patients were classified (using diagnostic and intervention codes as well as admission creatinine values) into the following groups: ESRD, CKD, AKI, acute-on-chronic disease (AoC) or no renal dysfunction (control). Primary outcome was all-cause mortality. Secondary outcome was ESRD incidence. RESULTS: Of 103,363 patients 4,192 had pre-existing CKD; 1389 had ESRD; 5273 developed AKI and 998 CKD patients developed AoC. One-year mortality was greatest in AoC patients (54 %) followed by AKI (48.7 %), CKD (47.6 %) and ESRD (40.3 %) (P < 0.001). Five-year mortality was highest for the CKD and AoC groups (71.3 % and 68.2 %, respectively) followed by AKI (61.8 %) and ESRD (62.9 %) (P < 0.001). ESRD incidence was greatest in the AoC and CKD groups (adjusted incidence rate ratio (IRR) 259 (95 % confidence interval (CI) 156.9-429.1) and 96.4, (95 % CI 59.7-155.6) respectively) and elevated in AKI patients compared with controls (adjusted IRR 24 (95 % CI 3.9-42.0); P < 0.001). Risk factors independently associated with ESRD in 1-year survivors were, according to relative risk ratio, AoC (356; 95 % CI 69.9-1811), CKD (267; 95 % CI 55.1-1280), AKI (30; 95 % CI 5.98-154) and presence of elevated admission serum potassium (4.6; 95 % CI 1.30-16.40) (P < 0.001). CONCLUSIONS: Pre-ICU renal disease significantly increases risk of death compared with controls. Subjects with AoC disease had extreme risk of developing ESRD. All patients with CKD who survive critical care should receive a nephrology referral. CLINICAL TRIALS REGISTRATION NUMBER: NCT02424747 April 20th 2015.

Evolution of chronic renal impairment and long-term mortality after de novo acute kidney injury in the critically ill; a Swedish multi-centre cohort study.

INTRODUCTION: Acute Kidney Injury (AKI) is common in critical ill populations and its association with high short-term mortality is well established. However, long-term risks of death and renal dysfunction are poorly understood and few studies exclude patients with pre-existing renal disease, meaning outcome for de novo AKI has been difficult to elicit. We aimed to compare the long-term risk of Chronic Kidney Disease (CKD), End Stage Renal Disease (ESRD) and mortality in critically ill patients with and without severe de novo AKI. METHOD: This cohort study was conducted between 2005 and 2011 in Swedish intensive care units (ICU). Data from 130134 adult patients listed on the Swedish intensive care register-database was linked with other national registries. Patients with pre-existing CKD (4192) and ESRD (1389) were excluded, as were cases (26771) with incomplete data. Patients were classified according to AKI exposure during ICU admission. Outcome in the de novo AKI group was compared to the non-exposed (no-AKI) intensive care control group. Primary outcome was all-cause mortality. Follow-up ranged from one to seven years (median 2.1 years). Secondary outcomes were incidence of CKD and ESRD and median follow-up was 1.3 years. RESULTS: Of 97 782 patients, 5273 (5.4%) had de novo AKI. These patients had significantly higher crude mortality at one (48.4% vs. 24.6%) and five years (61.8% vs. 39.1%) compared to the control group. The first 30% of deaths in AKI patients occurred within 11 days of ICU admission whilst the 30-centile in the no-AKI group died by 748 days. CKD was significantly more common in AKI survivors at one year (6.0% vs. 0.44%) than in no-AKI group (adjusted incidence rate ratio (IRR) 7.6). AKI patients also had significantly higher rates of ESRD at one (2.0% vs. 0.08%) and at five years (3.9% vs. 0.3%) than those in the comparison group (adjusted IRR 22.5). CONCLUSION: This large cohort study demonstrated that de novo AKI is associated with increased short and long-term risk of death. AKI is independently associated with increased risk of CKD and ESRD as compared to an ICU control population. Severe de novo AKI survivors should be routinely followed-up and their renal function monitored.

Inhaled isoflurane sedation during therapeutic hypothermia after cardiac arrest: a case series.

OBJECTIVE: Therapeutic hypothermia in the ICU requires mechanical ventilation and sedation. Hypothermia reduces the metabolism of commonly used IV sedatives. The use of long-acting sedative agents may confound neurologic assessment. Volatile anesthetics have been reported to provide protection against ischemia-reperfusion injury and have been safely used in the ICU to provide sedation in trials with shorter wake-up times. There are no clinical studies in this setting. We describe a case series and discuss potential benefits. DESIGN: Retrospective study. SETTINGS: Ten-bed ICU, university hospital. PATIENTS: Twelve patients resuscitated from cardiac arrest with Glasgow Coma Scale score less than or equal to 4. INTERVENTION: Isoflurane sedation with the AnaConDa during 24 hours therapeutic hypothermia, until rewarming. MEASUREMENTS AND MAIN RESULTS: Data were extracted from the computerized ICU chart/monitors, hospital and prehospital charts, and the national death index. Patients were 49-76 years old. Median return of spontaneous circulation was 14 minutes. Glasgow Coma Scale scores were assessed within 24 hours from reaching normal body temperature and compared with outcomes at 6 months: six patients had poor Glasgow Coma Scale scores (< 8) that remained low and all died before 6-month follow-up, whereas another six patients had high scores (> 8) and survived to 6 months with good Cerebral Performance Category. In the ICU, four of the survivors were directly extubated after rewarming while two were once more sedated due to pneumonia requiring invasive ventilator therapy. All patients required norepinephrine to maintain adequate mean arterial pressure. Isoflurane sedation was changed to midazolam in two nonsurviving patients because of hemodynamic instability, which persisted despite the change. CONCLUSIONS: Sedation with volatile anesthetics during therapeutic hypothermia may be a feasible short-acting option with potential postconditioning effects protecting vital organs from ischemia-reperfusion injury. Its measurability and insignificant drug accumulation could facilitate early neurologic assessment. Prospective clinical trials are warranted.

ICU admittance by a rapid response team versus conventional admittance, characteristics, and outcome.

OBJECTIVE: To evaluate characteristics and outcome of ICU patients admitted from general wards based on mode of admittance, via a rapid response team or conventional contact. DESIGN: Observational prospective study. SETTING: General ICU of a university hospital. PATIENTS: : A total of 694 admissions to ICU from general wards. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between 2007 and 2009, two cohorts admitted to ICU from general wards were identified: those admitted by the rapid response team and those admitted in a conventional way. Patients admitted directly from the trauma room, the emergency department, operating room, other hospitals, or other ICUs were excluded. Of 694 admissions, 355 came through a rapid response team call. Rapid response team patients were older (p < 0.01), and they had more severe comorbidities, higher severity score (p < 0.01), and almost three times more often the diagnosis of severe sepsis (p < 0.01) than conventionally admitted patients. Rapid response team patients had higher ICU mortality and 30-day mortality with a crude odds ratio for mortality within 30 days of 1.57 (95% confidence interval 1.08-2.28). Adjusted for age and comorbidities however, the difference was no longer significant with an odds ratio of 1.11 (95% confidence interval 0.70-1.76). CONCLUSIONS: This study suggests that the rapid response team is an important system for identifying complex patients in need of intensive care. More than half of ICU admissions from the wards came through a rapid response team call. Compared with conventional admissions, rapid response team patients had a high proportion of characteristics that could be related to a worse prognosis. Severe sepsis at the wards was mainly detected by the rapid response team and was the most common admitting diagnosis among the rapid response team patients. When adjusted for confounding factors, outcome between the groups did not differ, supporting the use of rapid response systems to identify deteriorating ward patients.

Association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with sepsis and acute kidney dysfunction.

OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL) is secreted by injured kidney cells as well as by activated neutrophils in response to bacterial infections. We assessed the influence of acute renal dysfunction on the association between plasma NGAL and sepsis. METHODS: NGAL was measured daily in 138 critically ill patients. Simultaneous recordings of sepsis status and fluctuations in renal function were made. RESULTS: Elevated NGAL was associated with sepsis independent of level of acute renal dysfunction. A cut-off value of 98 ng/mL distinguished sepsis from systemic inflammation with high sensitivity (0.77) and specificity (0.79). CONCLUSIONS: Plasma NGAL can help clinicians to identify bacterial infections in critically ill patients.

Impact of sepsis on levels of plasma cystatin C in AKI and non-AKI patients.

BACKGROUND: Cystatin C is a marker of acute kidney injury (AKI). However, systemic inflammation associated with sepsis, a common AKI-trigger, may affect cystatin C. We studied the impact of sepsis on cystatin C levels in plasma. Furthermore, we investigated whether the presence of sepsis affects the predictive properties of cystatin C. METHODS: Three hundred and twenty-seven intensive care unit (ICU) patients were categorized as having: neither AKI nor sepsis (n = 151), sepsis without AKI (n = 80), AKI without sepsis (n = 24) or AKI and sepsis (n = 72) during their first week in the ICU. Changes in cystatin C and creatinine over time in patients with and without sepsis or AKI were analysed using repeated measures analysis of variance. The performance of cystatin C on admission to predict sustained AKI, worsened AKI or death was assessed from the area under the receiver-operating characteristic curve (AUC-ROC) in septic and non-septic patients separately. RESULTS: In non-AKI patients, cystatin C increased and creatinine decreased significantly over the first week. The change in cystatin C or creatinine did not differ significantly between septic and non-septic patients without AKI. Even in AKI patients, the cystatin C change did not differ significantly between septic and non-septic patients. The AUC-ROCs for prediction of the composite outcome were 0.80 and 0.78 in patients with and without sepsis, respectively, and did not differ significantly (P = 0.76). CONCLUSION: The inflammatory response induced by sepsis has no impact on the levels of cystatin C in plasma during the first week in the ICU.

Pathogens in the lower respiratory tract of intensive care unit patients: impact of duration of hospital care and mechanical ventilation.

BACKGROUND: Ventilator-associated pneumonia (VAP), the most common hospital-acquired infection in intensive care unit (ICU) patients, is caused by bacteria in the lower respiratory tract of mechanically ventilated patients. METHODS: The current study was focused on 443 bacterial isolates from the lower respiratory tract of mechanically ventilated ICU patients (n = 346) in a Swedish University Hospital. Data were obtained from a prospective infection control database covering 9 y (2002-2010). We analysed the correlation between duration of hospital care and mechanical ventilation at the time of sampling on the occurrence of different pathogens. RESULTS: Duration of hospital care and mechanical ventilation prior to sampling was similarly short for Streptococcus pneumoniae, beta-streptococci, and Haemophilus influenzae (≤ 2 days). In contrast, duration of hospital care and mechanical ventilation were longest for Stenotrophomonas maltophilia (6 and 11 days). For Staphylococcus aureus, the most common Gram-positive isolate, the duration was longer than for S. pneumoniae but shorter than for most Gram-negative bacteria. With the exception of S. maltophilia and Pseudomonas aeruginosa, the median duration of mechanical ventilation was short and similar for most bacteria. In samples taken on the first day of mechanical ventilation, the rate of pathogens expected to be resistant to cefotaxime was 23%. CONCLUSIONS: The occurrence of pathogens with high antibiotic resistance in the lower respiratory tract increases with increased duration of hospital care and mechanical ventilation. An equally important result is that pathogens resistant to third-generation cephalosporins were more common than expected, even after a very short duration of hospital care and mechanical ventilation.

Cystatin C is correlated with mortality in patients with and without acute kidney injury.

BACKGROUND: Recent research has shown cystatin C to predict mortality and cardiovascular morbidity independent of renal function. The aim of this study was to evaluate the prognostic value of cystatin C on mortality in adult general ICU patients with acute kidney injury (AKI). We later expanded the study and included patients without signs of AKI. METHODS: A total of 845 ICU patients were analysed for cystatin C and classified according to the RIFLE criteria. Of these, 271 patients with either creatinine >150 micromol/l, urea >25 or anuria/oliguria entered the AKI cohort. The remaining 562 patients entered the non-AKI cohort. Both cohorts were divided into quartiles according to cystatin C at entry. In the non-AKI cohort, we split the highest cystatin C quartile into two. The relationship between the different cystatin C quartiles and mortality in patients with and without AKI was estimated by hazard ratios (HR) derived from the Cox proportional hazards regression model. RESULTS: A relationship between cystatin C and mortality was found in patients with and without AKI, being stronger in patients without AKI. In AKI patients, the HR comparing cystatin C above and below the median more than doubled from the second year on compared to the first year follow-up. After exclusion of patients in the non-AKI cohort with 'potential AKI' (creatinine >100 micromol/l or urea > 20 mmol/l), the correlation between cystatin C levels and risk of death was strengthened. CONCLUSIONS: Cystatin C is correlated with mortality independently of renal function measured by creatinine in patients entering the general ICU.

Performance of plasma measurement of neutrophil gelatinase-associated lipocalin as a biomarker of bacterial infections in the intensive care unit.

PURPOSE: To assess the value of dimeric neutrophil-gelatinase associated lipocalin (NGAL) as an early marker of bacterial infection and its response to antibiotic therapy in intensive care unit (ICU) patients. MATERIALS & METHODS: We measured daily plasma dNGAL in 198 patients admitted to a mixed ICU. Likelihood of infection was determined with International Sepsis Forum criteria. We measured dNGAL in 145 healthy controls to establish normal values. RESULTS: ICU patients had higher dNGAL than healthy controls. A suspected or confirmed infection was independently associated with 90% (95% CI 15-215%) higher dNGAL than absence of infection. We observed no association between acute kidney injury and dNGAL. Diagnostic accuracy at antibiotic treatment initiation, assessed with area under the receiver-operating characteristics curve (AUC-ROC), for dNGAL was 0.70 (95% CI 0.60-0.79). AUC-ROC for dNGAL 24 h before antibiotic treatment initiation was 0.54 (95% CI 0.41-0.66). The mean (95% CI) change of dNGAL in the first 2 days after appropriate antibiotic therapy initiation was -31 (-49,-13)%. CONCLUSIONS: In our cohort of ICU patients, plasma dNGAL was associated with presence of bacterial infections independent of AKI but it performed poor as a predictor of infections. Following antibiotic therapy, dNGAL markedly decreased-supporting further exploration of dNGAL-guided antibiotic de-escalation.

End-stage renal disease patients on renal replacement therapy in the intensive care unit: short- and long-term outcome.

OBJECTIVE: The number of patients with end-stage renal disease has increased during the last decades. Data shows that 10% of the renal replacement therapy population in the intensive care unit are patients with end-stage renal disease. We aimed to describe the short- and long-term outcome of these patients after renal replacement therapy in the intensive care unit. DESIGN: Nationwide cohort study between the years 1995 and 2004. Follow-up up to 5 years. SETTING: Swedish general intensive care units and Swedish hospitals. PATIENTS: Eligible subjects were end-stage renal disease patients treated with renal replacement therapy in 32 Swedish general intensive care units. In total, 245 patients were studied. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Short- and long-term mortality was studied. Logistic regression was used to analyze short-term mortality. Long-term mortality was compared with the mortality of end-stage renal disease patients outside the intensive care unit and the mortality in the population. Diabetes and heart failure are significant risk factors for 90-day mortality, with an odds ratio of 1.9 and 2.0, respectively. The intensive care unit end-stage renal disease cohort had increased long-term mortality as compared with non-intensive care unit end-stage renal disease patients, relative risk of death 2.32 (confidence interval 1.84-2.92). A comparison with the mortality rate in the general population yielded a standardized mortality ratio of 25 (95% confidence interval: 19.6-31.4). CONCLUSIONS: For end-stage renal disease patients in the intensive care unit, age, diabetes mellitus, and heart failure are risk factors for 90-day mortality. Long-term mortality is associated with age and heart failure. The long-term mortality of end-stage renal disease patients surviving the intensive care unit stay is significantly higher compared with end-stage renal disease patients without a known intensive care unit admission.

Short- and long-term follow-up of intensive care unit patients after sedation with isoflurane and midazolam--a pilot study.

OBJECTIVE: To compare memories from the intensive care unit (ICU) and short- and long-term psychological morbidity in patients after sedation with intravenous midazolam or inhaled isoflurane. DESIGN: Prospective long-term follow-up after randomized controlled trial. SETTING: General ICU at Karolinska University Hospital, Solna, Stockholm. PATIENTS: Forty patients in need of sedation during ventilator treatment. INTERVENTIONS: Patients were randomized to receive isoflurane or midazolam for goal-directed sedation until extubation or for a maximum of 96 hrs. MEASUREMENTS AND MAIN RESULTS: For short-term follow-up, doctors', nurses', and physiotherapists' notes from the 4 days following exposure to the study drugs were reviewed for words indicating adequate or pathologic cognitive and psychological recovery. For long-term follow-up, all 6-month survivors received questionnaires including the ICU Memory Tool (ICU-MT), Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), and Well-Being Index. Additionally, several screening questions for previous posttraumatic stress symptoms were included. In the short term follow-up, no significant differences were found between groups. In the long-term follow-up, a trend toward fewer hallucinations/delusions after isoflurane sedation than after midazolam (two of ten isoflurane patients vs. five of seven midazolam patients) was found (p = .06). None of the five solely isoflurane-sedated patients reported hallucinations/delusions from the ICU. There was no difference in groups in long-term psychological morbidity as measured with HADS and IES. Memories of negative feelings in the ICU (ICU-MT) were associated with high HADS and IES scores (Fisher's exact test, p = .02 and p = .01, respectively). CONCLUSIONS: Sedation of ICU patients with isoflurane may result in fewer delusional memories or hallucinations from the ICU compared with more commonly used intravenous sedation. Memories of negative feelings from the ICU were associated with symptoms of depression or anxiety or symptoms indicating posttraumatic stress disorder. Further study of memory and cognitive/psychological recovery after prolonged isoflurane sedation beyond 96 hrs is warranted.

Creatinine- and Cystatin C-Based Incidence of Chronic Kidney Disease and Acute Kidney Disease in AKI Survivors.

BACKGROUND: Renal dysfunction after acute kidney injury (AKI) is common, potentially modifiable, but poorly understood. Acute kidney disease (AKD) describes renal dysfunction 7 to 90 days after AKI and is determined by percentage change in creatinine from baseline. Chronic kidney disease (CKD) is defined as the estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m2 persisting for more than 90 days. We compared CKD incidence using both creatinine- and cystatin C-based GFR with AKD incidence at 90 days in AKI survivors. METHODS: A prospective cohort study was conducted in a Swedish intensive care unit (ICU) between 2008 and 2010. We included AKI patients alive at 90 days. We excluded patients <18 and >100 years, death before follow-up, CKD prior to admission, and follow-up before 60 days or beyond 270 days. Creatinine and cystatin C were measured at 90 days and converted to eGFR (mL/min/1.73 m2). RESULTS: We included 274 patients. At 90-day follow-up, the median creatinine eGFR (MDRD) was 81.6 (IQR 58.6-106.8) and median cystatin C eGFR was 51.5 (IQR 35.8-70.7). The incidence of CKD (eGFR < 60) was 25.8% based on creatinine but 63.7% using cystatin C estimates. AKD was present in 47 patients (18.9%). Age, discharge cystatin C, creatinine at discharge, and female gender predicted creatinine-defined CKD at follow-up. Age, discharge cystatin C, CRRT on ICU, and diabetes were associated with cystatin C-based CKD. CONCLUSIONS: In AKI survivors followed up at 3 months, CKD criteria were met in a quarter of patients using creatinine and in two-thirds using cystatin C eGFR. Less than one-fifth of patients fulfilled AKD criteria. The application of AKD criteria may underestimate renal dysfunction in AKI survivors.

Continuous renal replacement therapy is associated with less chronic renal failure than intermittent haemodialysis after acute renal failure.

OBJECTIVE: Acute renal failure can be treated with continuous renal replacement therapy (CRRT) or intermittent haemodialysis (IHD). Whether this choice affects renal recovery has been debated, since it has implications on quality of life and costs. Our objective was to determine the impact of CRRT and IHD on renal recovery. DESIGN: Nationwide retrospective cohort study between the years 1995 and 2004. Follow-up ranged between 3 months and 10 years. SETTING: Thirty-two Swedish intensive care units. PATIENTS AND PARTICIPANTS: Eligible subjects were adults treated in Swedish general intensive care units with RRT. A total of 2,642 patients from 32 ICUs were included. We then excluded patients with end-stage renal disease (252) and patients lacking a diagnosis in the in-patient register (188). Thus, 2,202 patients were studied. Follow-up was complete. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The primary outcome was renal recovery. Secondarily we studied the mortality of the cohort. There were no differences between IHD and CRRT patients regarding baseline characteristics, such as age, sex and comorbidities. Of the 1,102 patients surviving 90 days after inclusion in the cohort, 944 (85.7%) were treated with CRRT and 158 (14.3%) were treated with IHD. Seventy-eight patients (8.3%; confidence interval, CI, 6.6-10.2), never recovered their renal function in the CRRT group. The proportion was significantly higher among IHD patients, where 26 subjects or 16.5% (CI 11.0-23.2) developed need for chronic dialysis. CONCLUSIONS: The use of CRRT is associated with better renal recovery than IHD, but mortality does not differ between the groups.

Long-term outcome after intensive care: can we protect the kidney?

Long-term outcome--mortality, morbidity and quality of life--is finally receiving attention in the field of intensive care research. A number of recent studies have focused on patient survival and kidney survival after acute renal failure. The present review focuses on the third publication from the Beginning and Ending Supportive Therapy for the Kidney Investigators Writing Committee. Their study took place in 54 intensive care units in 23 countries. The main findings of the Beginning and Ending Supportive Therapy study was that the choice of continuous renal replacement therapy as the initial therapy is not a predictor of hospital survival or of dialysis-free hospital survival, but that it is an independent predictor of renal recovery among survivors. In conclusion, the critical care research community needs to focus on long-term outcome. A number of recent studies of acute renal failure have done just that.

Calprotectin as an early biomarker of bacterial infections in critically ill patients: an exploratory cohort assessment.

BACKGROUND: Calprotectin is the most abundant protein in the cytosolic fraction of neutrophils, and neutrophil degranulation is a major response to bacterial infections. OBJECTIVES: To assess the value of plasma calprotectin as an early marker of bacterial infections in critically ill patients and compare it with the corresponding values for procalcitonin (PCT), C-reactive protein (CRP) and white blood cell count (WBC). METHODS: We measured daily plasma calprotectin levels in 110 intensive care unit patients using a newly developed turbidimetric assay run on clinical chemistry analysers. The likelihood of infection was determined according to the International Sepsis Forum criteria. RESULTS: Overall, 58 patients (52.7%) developed a suspected or confirmed bacterial infection. Plasma calprotectin predicted such infections within 24 hours with an area under the receiver operating characteristics curve (ROC area) of 0.78 (95% CI, 0.68-0.89). The ROC area for calprotectin was significantly greater than the corresponding ROC areas for WBC (P < 0.001) and PCT (P = 0.02) but only marginally better than the ROC area for CRP (0.71; 95% CI, 0.68-0.89). CONCLUSION: Plasma calprotectin appears to be a useful early marker of bacterial infections in critically ill patients, with better predictive characteristics than WBC and PCT.

Prevalence and sensitivity of MET-criteria in a Scandinavian University Hospital.

OBJECTIVE: To make a preliminary estimation of the workload for a medical emergency team (MET) in a Scandinavian University Hospital by recording prevalent physiological data on all adult patients and to see if the patients with deviating physiology (i.e. fulfilling the study criteria, in essence a set of simplified MET-criteria) had an elevated mortality. We also tested sensitivity and specificity by altering the cut-off levels of the calling criteria. DESIGN: Cross sectional prevalence study. SETTING: University hospital in the capital of Sweden. PATIENTS: Adult patients treated in the general wards of the hospital. Patients from psychiatric wards and intensive care units were excluded from the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 4.5% of the scored patients fulfilled the study criteria. These patients had a 30-day mortality of 25% (confidence interval 12.7-41.2) as compared to 3.5% (2.4-5) for the patients not fulfilling the study criteria. Extended criteria revealed 18 deaths within 30 days, 8 more deaths than the original study criteria. However, 123 patients - equalling 13.8% of the cohort (CI 11.6-16.2) - fulfilled these criteria as compared to the 40 patients fulfilling the original study criteria. Thus, the 30-day mortality of the patients with positive extended criteria totalled 14.6% (CI 8.9-22.1). Restricted criteria showed a mere 20 patients (2.2%; CI 1.4-3.5) and only 4 deaths, making 30-day mortality 20% (CI 5.7-43.7); thus, sensitivity was actually lower using restricted criteria. CONCLUSIONS: Even these modified - and simplified - MET-criteria proved to be able to single out patients with elevated mortality as compared to the rest of the hospital population. Extending the criteria significantly lowered sensitivity and would extend the MET-workload enormously. Restricting the criteria led to missed mortalities where intervention could be beneficial. The results suggest that a routine use of simple physiological tests can be of help in the identification of patients at risk.

Intra-day variability of cystatin C, creatinine and estimated GFR in intensive care patients.

BACKGROUND: Markers of renal function are widely used in intensive care and sudden changes are important indicators of acute kidney injury. The problem is to distinguish between disease progression/improvement from the natural variation in the patient. The aim of the present study was thus to study the normal intraday variation in ICU patients. METHODS: We studied the intra-day variation of creatinine, cystatin C and estimated GFR based on these two markers in 28 clinically stable ICU patients. RESULTS: The median diurnal coefficient of variation sCV) for creatinine was 3.70% (1.92-9.25%) while the median CV for cystatin C was 3.66% (1.36-8.11%). The corresponding CVs for the estimated GFRs were 2.00% (0.89-9.82%) for eGFRcreatinine and 4.60% (1.65-10.24%) for eGFRcystc. CONCLUSIONS: The eGFRcreatinine values in individual patients were clearly higher than the eGFRcystc values. The median CV for creatinine, cystatin C and the eGFR measurements were below 5% which means that 95% of the test results will vary by <10% between sampling times in stable ICU patients. Differences >10% between sampling times are thus likely to be an indication of changes in biomarker levels due to the disease/treatment.

Plasma endostatin may improve acute kidney injury risk prediction in critically ill patients.

BACKGROUND: Breakdown of renal endothelial, tubular and glomerular matrix collagen plays a major role in acute kidney injury (AKI) development. Such collagen breakdown releases endostatin into the circulation. The aim of this study was to compare the AKI predictive value of plasma endostatin with two previously suggested biomarkers of AKI, cystatin C and neutrophil gelatinase-associated lipocalin (NGAL). METHODS: We studied 93 patients without kidney disease who had a first plasma sample obtained within 48 h of ICU admission. We identified risk factors for AKI within the population and designed a predictive model. The individual ability and net contribution of endostatin, cystatin C and NGAL to predict AKI were evaluated by the area under the receiver operating characteristics curve (AUC), likelihood-ratio test, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: In total, 21 (23 %) patients experienced AKI within 72 h. A three-parameter model (age, illness severity score and early oliguria) predicted AKI with an AUC of 0.759 (95 % CI 0.646-0.872). Adding endostatin to the predictive model significantly (P = 0.04) improved the AUC to 0.839 (95 % CI 0.752-0.925). In addition, endostatin significantly improved risk prediction using the likelihood-ratio test (P = 0.005), NRI analysis (0.27; P = 0.04) and IDI analysis (0.07; P = 0.04). In contrast, adding cystatin C or NGAL to the three-parameter model did not improve risk prediction in any of the four analyses. CONCLUSIONS: In this cohort of critically ill patients, plasma endostatin improved AKI prediction based on clinical risk factors, while cystatin C and NGAL did not.