Azrina Ralib

Test Characteristics of Urinary Biomarkers Depend on Quantitation Method in Acute Kidney Injury

The concentration of urine influences the concentration of urinary biomarkers of AKI. Whether normalization to urinary creatinine concentration, as commonly performed to quantitate albuminuria, is the best method to account for variations in urinary biomarker concentration among patients in the intensive care unit is unknown. Here, we compared the diagnostic and prognostic performance of three methods of biomarker quantitation: absolute concentration, biomarker normalized to urinary creatinine concentration, and biomarker excretion rate. We measured urinary concentrations of alkaline phosphatase, γ-glutamyl transpeptidase, cystatin C, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and IL-18 in 528 patients on admission and after 12 and 24 hours. Absolute concentration best diagnosed AKI on admission, but normalized concentrations best predicted death, dialysis, or subsequent development of AKI. Excretion rate on admission did not diagnose or predict outcomes better than either absolute or normalized concentration. Estimated 24-hour biomarker excretion associated with AKI severity, and for neutrophil gelatinase-associated lipocalin and cystatin C, with poorer survival. In summary, normalization to urinary creatinine concentration improves the prediction of incipient AKI and outcome but provides no advantage in diagnosing established AKI. The ideal method for quantitating biomarkers of urinary AKI depends on the outcome of interest.

The urine output definition of acute kidney injury is too liberal

IntroductionThe urine output criterion of 0.5 ml/kg/hour for 6 hours for acute kidney injury (AKI) has not been prospectively validated. Urine output criteria for AKI (AKIUO) as predictors of in-hospital mortality or dialysis need were compared.MethodsAll admissions to a general ICU were prospectively screened for 12 months and hourly urine output analysed in collection intervals between 1 and 12 hours. Prediction of the composite of mortality or dialysis by urine output was analysed in increments of 0.1 ml/kg/hour from 0.1 to 1 ml/kg/hour and the optimal threshold for each collection interval determined. AKICr was defined as an increase in plasma creatinine ≥26.5 μmol/l within 48 hours or ≥50% from baseline.ResultsOf 725 admissions, 72% had either AKICr or AKIUO or both. AKIUO (33.7%) alone was more frequent than AKICr (11.0%) alone (P <0.0001). A 6-hour urine output collection threshold of 0.3 ml/kg/hour was associated with a stepped increase in in-hospital mortality or dialysis (from 10% above to 30% less than 0.3 ml/kg/hour). Hazard ratios for in-hospital mortality and 1-year mortality were 2.25 (1.40 to 3.61) and 2.15 (1.47 to 3.15) respectively after adjustment for age, body weight, severity of illness, fluid balance, and vasopressor use. In contrast, after adjustment AKIUO was not associated with in-hospital mortality or 1-year mortality. The optimal urine output threshold was linearly related to duration of urine collection (r2 = 0.93).ConclusionsA 6-hour urine output threshold of 0.3 ml/kg/hour best associated with mortality and dialysis, and was independently predictive of both hospital mortality and 1-year mortality. This suggests that the current AKI urine output definition is too liberally defined. Shorter urine collection intervals may be used to define AKI using lower urine output thresholds.

Combining creatinine and volume kinetics identifies missed cases of acute kidney injury following cardiac arrest

IntroductionFluid resuscitation in the critically ill often results in a positive fluid balance, potentially diluting the serum creatinine concentration and delaying diagnosis of acute kidney injury (AKI).MethodsDilution during AKI was quantified by combining creatinine and volume kinetics to account for fluid type, and rates of fluid infusion and urine output. The model was refined using simulated patients receiving crystalloids or colloids under four glomerular filtration rate (GFR) change scenarios and then applied to a cohort of critically ill patients following cardiac arrest.ResultsThe creatinine concentration decreased during six hours of fluid infusion at 1 litre-per-hour in simulated patients, irrespective of fluid type or extent of change in GFR (from 0% to 67% reduction). This delayed diagnosis of AKI by 2 to 9 hours. Crystalloids reduced creatinine concentration by 11 to 19% whereas colloids reduced concentration by 36 to 43%. The greatest reduction was at the end of the infusion period. Fluid dilution alone could not explain the rapid reduction of plasma creatinine concentration observed in 39 of 49 patients after cardiac arrest. Additional loss of creatinine production could account for those changes. AKI was suggested in six patients demonstrating little change in creatinine, since a 52 ± 13% reduction in GFR was required after accounting for fluid dilution and reduced creatinine production. Increased injury biomarkers within a few hours of cardiac arrest, including urinary cystatin C and plasma and urinary Neutrophil-Gelatinase-Associated-Lipocalin (biomarker-positive, creatinine-negative patients) also indicated AKI in these patients.ConclusionsCreatinine and volume kinetics combined to quantify GFR loss, even in the absence of an increase in creatinine. The model improved disease severity estimation, and demonstrated that diagnostic delays due to dilution are minimally affected by fluid type. Creatinine sampling should be delayed at least one hour following a large fluid bolus to avoid dilution. Unchanged plasma creatinine post cardiac arrest signifies renal injury and loss of function.Trial registrationAustralian and New Zealand Clinical Trials Registry ACTRN12610001012066.

The clinical utility window for acute kidney injury biomarkers in the critically ill

IntroductionAcute Kidney Injury (AKI) biomarker utility depends on sample timing after the onset of renal injury. We compared biomarker performance on arrival in the emergency department (ED) with subsequent performance in the intensive care unit (ICU).MethodsUrinary and plasma Neutrophil Gelatinase-Associated Lipocalin (NGAL), and urinary Cystatin C (CysC), alkaline phosphatase, γ-Glutamyl Transpeptidase (GGT), α- and π-Glutathione S-Transferase (GST), and albumin were measured on ED presentation, and at 0, 4, 8, and 16 hours, and days 2, 4 and 7 in the ICU in patients after cardiac arrest, sustained or profound hypotension or ruptured abdominal aortic aneurysm. AKI was defined as plasma creatinine increase ≥26.5 μmol/l within 48 hours or ≥50% within 7 days.ResultsIn total, 45 of 77 patients developed AKI. Most AKI patients had elevated urinary NGAL, and plasma NGAL and CysC in the period 6 to 24 hours post presentation. Biomarker performance in the ICU was similar or better than when measured earlier in the ED. Plasma NGAL diagnosed AKI at all sampling times, urinary NGAL, plasma and urinary CysC up to 48 hours, GGT 4 to 12 hours, and π-GST 8 to 12 hours post insult. Thirty-one patients died or required dialysis. Peak 24-hour urinary NGAL and albumin independently predicted 30-day mortality and dialysis; odds ratios 2.87 (1.32 to 6.26), and 2.72 (1.14 to 6.48), respectively. Urinary NGAL improved risk prediction by 11% (IDIevent of 0.06 (0.002 to 0.19) and IDInon-event of 0.04 (0.002 to 0.12)).ConclusionEarly measurement in the ED has utility, but not better AKI diagnostic performance than later ICU measurement. Plasma NGAL diagnosed AKI at all time points. Urinary NGAL best predicted mortality or dialysis compared to other biomarkers.Trial registrationAustralian and New Zealand Clinical Trials Registry ACTRN12610001012066. Registered 12 February 2010

The diagnostic ability of procalcitonin and interleukin-6 to differentiate infectious from noninfectious systemic inflammatory response syndrome and to predict mortality

PURPOSE The purpose of the study was to quantify the ability of procalcitonin (PCT) and interleukin-6 (IL-6) to differentiate noninfectious systemic inflammatory response syndrome (SIRS) and sepsis and to predict hospital mortality. MATERIALS We recruited consecutively adult patients with SIRS admitted to an intensive care unit. They were divided into sepsis and noninfectious SIRS based on clinical assessment with or without positive cultures. Concentrations of PCT and IL-6 were measured daily over the first 3 days. RESULTS A total of 239 patients were recruited, 164 (68.6%) had sepsis, and 68 (28.5%) died in hospital. The PCT levels were higher in sepsis compared with noninfectious SIRS throughout the 3-day period (P < .0001). On admission, PCT concentration was diagnostic of sepsis (area under the curve of 0.63 [0.55-0.71]), and IL-6 was predictive of mortality, (area under the curve of 0.70 [0.62-0.78]). Peak IL-6 concentration improved the risk assessment of Sequential Organ Failure Assessment (SOFA) score for prediction of mortality among those who went on to die by an average of 5% and who did not die by 2% CONCLUSIONS Procalcitonin measured on intensive care unit admission was diagnostic of sepsis, and IL-6 was predictive of mortality. Addition of IL-6 concentration to SOFA score improved risk assessment for prediction of mortality. Future studies should include clinical indices, for example, SOFA score, for prognostic evaluation of biomarkers.

Procalcitonin Clearance for Early Prediction of Survival in Critically Ill Patients with Severe Sepsis

Introduction. Serum procalcitonin (PCT) diagnosed sepsis in critically ill patients; however, its prediction for survival is not well established. We evaluated the prognostic value of dynamic changes of PCT in sepsis patients. Methods. A prospective observational study was conducted in adult ICU. Patients with systemic inflammatory response syndrome (SIRS) were recruited. Daily PCT were measured for 3 days. 48 h PCT clearance (PCTc-48) was defined as percentage of baseline PCT minus 48 h PCT over baseline PCT. Results. 95 SIRS patients were enrolled (67 sepsis and 28 noninfectious SIRS). 40% patients in the sepsis group died in hospital. Day 1-PCT was associated with diagnosis of sepsis (AUC 0.65 (95% CI, 0.55 to 0.76)) but was not predictive of mortality. In sepsis patients, PCTc-48 was associated with prediction of survival (AUC 0.69 (95% CI, 0.53 to 0.84)). Patients with PCTc-48 > 30% were independently associated with survival (HR 2.90 (95% CI 1.22 to 6.90)). Conclusions. PCTc-48 is associated with prediction of survival in critically ill patients with sepsis. This could assist clinicians in risk stratification; however, the small sample size, and a single-centre study, may limit the generalisability of the finding. This would benefit from replication in future multicentre study.Introduction. Serum procalcitonin (PCT) diagnosed sepsis in critically ill patients; however, its prediction for survival is not well established. We evaluated the prognostic value of dynamic changes of PCT in sepsis patients. Methods. A prospective observational study was conducted in adult ICU. Patients with systemic inflammatory response syndrome (SIRS) were recruited. Daily PCT were measured for 3 days. 48 h PCT clearance (PCTc-48) was defined as percentage of baseline PCT minus 48 h PCT over baseline PCT. Results. 95 SIRS patients were enrolled (67 sepsis and 28 noninfectious SIRS). 40% patients in the sepsis group died in hospital. Day 1-PCT was associated with diagnosis of sepsis (AUC 0.65 (95% CI, 0.55 to 0.76)) but was not predictive of mortality. In sepsis patients, PCTc-48 was associated with prediction of survival (AUC 0.69 (95% CI, 0.53 to 0.84)). Patients with PCTc-48 > 30% were independently associated with survival (HR 2.90 (95% CI 1.22 to 6.90)). Conclusions. PCTc-48 is associated with prediction of survival in critically ill patients with sepsis. This could assist clinicians in risk stratification; however, the small sample size, and a single-centre study, may limit the generalisability of the finding. This would benefit from replication in future multicentre study.

Acute kidney injury in a Malaysian intensive care unit: assessment of incidence, risk factors and outcome

PURPOSE Acute kidney injury (AKI) is common and carries a high mortality rate. Most epidemiological studies were retrospective and were done in Western populations. We aim to assess its incidence using both urine output and creatinine criteria and its association with risk factors and outcome. MATERIAL AND METHODS This was a single-center, prospective, observational study. All intensive care unit (ICU) patients older than 18 years were screened for inclusion in the study. Admission of less than 48 hours, postelective surgery, and ICU readmission were excluded. RESULTS A total of 143 patients were recruited, of these, 65% had AKI, of which 18 (19%) were stage 1; 23 (25%), stage 2; and 52 (56%), stage 3. Independent risk factors for AKI include high Acute Physiology and Chronic Health Evaluation II score and septic shock (odds ratio of 1.20 [1.09-1.33] and 8.41 [1.49-47.6], respectively). Thirty-eight percent were classified as AKI based on creatinine and 61% as AKI based on urine output criteria, and, in 34%, both AKI based on creatinine and AKI based on urine output criteria were present. Acute kidney injury was an independent risk factor for mortality (hazard ratio of, 2.61 [1.06-6.42]). CONCLUSIONS Acute kidney injury is common in our ICU, and almost half are of highest severity stage. Patients with high severity of illness and septic shock were at risk for AKI. The presence of AKI independently predicted mortality.

Performance of STAR virtual trials for diabetic and non-diabetic in HTAA intensive care unit

Critically ill patients are commonly linked to stress-induced hyperglycaemia which relates to insulin resistance and the risk of per-diagnosed with diabetes and other metabolic illnesses. Thus, it is essential to choose the best practice of blood glucose management in order to reduce morbidity and mortality rates in intensive care unit. This study is focusing on clinical data of 210 critically ill patients in Hospital Tengku Ampuan Afzan (HTAA), Kuantan who underwent Intensive Insulin Therapy which utilized a sliding scale method. Patients were identified in two main groups of diabetic (123) and non-diabetic (87) where stochastic model is generated to observe 90% confidence interval of insulin sensitivity. Blood glucose levels comparison between these two cohorts is conducted to observe the percentage of blood glucose levels within targeted band of 4.4–10.0 mmol/L. It is found that 82% of BG levels are within tar gated band for non-diabetes cohort under stochastic targeted (STAR) glycaemic control protocol. However, only 59.6% and 70.6% BG levels are within targeted band for diabetes cohort for insulin infusion therapy used in HTAA and STAR protocols. Thus, further investigation on blood glucose control protocol for diabetes patients is required to increase the reliability and efficacy of current practice despite of patient safety.

High frequency oscillatory ventilation in leptospirosis pulmonary hemorrhage syndrome: A case series study.

Hypoxemia in severe leptospirosis-associated pulmonary hemorrhage syndrome (LPHS) is a challenging clinical scenario not usually responsive to maximal support on mechanical ventilation. We described the efficacy and safety of high frequency oscillatory ventilation (HFOV) as rescue therapy in acute respiratory failure secondary to LPHS. This is a retrospective case study of five patients with diagnosis of severe LPHS, who were admitted to Intensive Care Unit from October 2014 to January 2015. They developed refractory hypoxemia on conventional mechanical ventilation and rescue therapy was indicated. All patients responded rapidly by showing improvements in oxygen index and PaO2/FiO2 ratio within first 72 h of therapy. Despite severity of illness evidenced by high Simplified Acute Physiological II and Sequential Organ Failure Assessment scores, all patients were discharged from hospital alive. In view of the rapid onset and extent of hemorrhage which may culminate quickly into asphyxiation and death, HFOV may indeed be lifesaving in severe LPHS.

Plasma Neutrophil Gelatinase Associated Lipocalin Diagnosed Acute Kidney Injury in Patients With Systemic Inflammatory Disease And Sepsis.

Sepsis is the leading cause of intensive care unit (ICU) admission. Plasma Neutrophil Gelatinase Associated‐Lipocalin (NGAL) is a promising biomarker for acute kidney injury (AKI) detection; however, it is also increased with inflammation and few studies have been conducted in non‐Caucasian populations and/or in developing economies. Therefore, we evaluated plasma NGALs diagnostic performance in the presence of sepsis and systemic inflammatory response syndrome (SIRS) in a Malaysian ICU cohort.