Blood Test IDs Acute Kidney Injury in ED

A test that measures blood levels of neutrophil gelatinase-associated lipocalin (NGAL) accurately distinguished between acute kidney injury and reversible transient kidney dysfunction in the ED, researchers reported.

Among 616 patients with varying urgent health issues presenting to a hospital emergency department, the highest median levels of plasma NGAL were seen in those with acute kidney injury (146-174 ng/ml at various time points); levels also increased with acute kidney injury (AKI) severity (207-244 ng/ml for AKI Network stage 2 or greater disease).

Plasma NGAL also discriminated between patients with AKI, those with normal kidney function, and those with transient azotemia (area under the curve, 0.85 and 0.73, respectively); a plasma NGAL level of 133 ng/ml or greater was associated with a 10-fold increase in AKI risk, Prasad Devarajan, MD, and colleagues from Cincinnati Children's Hospital Medical Center and the Hospital Fernando Fonseca in Lisbon, Portugal wrote in the Sept. 5 issue of the Clinical Journal of the American Society of Nephrology.

AKI has been increasing in both the hospital and community settings, but diagnosis of the condition remains problematic, the researchers wrote.

Serum creatinine (SCr) is routinely used in emergency departments to diagnose AKI, but it's a delayed marker that rises only after kidney injury has been established, and there are other downsides to the test, Devarajan told MedPage Today.

"Especially in the community-acquired setting, it is very common to see an increase in SCr," he said. "In this setting it is very important to be able to distinguish between true, intrinsic AKI and transient, reversible kidney injury ... [I]n both cases SCr is going to be elevated."

Along with colleagues at Cincinnati Children's Hospital, Devarajan developed the NGAL test as a biomarker of early AKI. In earlier studies, the researchers showed it to be useful in a variety of hospital settings, including adult ICU and heart failure patients.

      Devarajan holds patents on the test, which is being commercially developed by the point-of-care diagnostic and services company Alere, Inc. of Waltham, Massachusetts. The test has been approved in parts of Europe and Asia, and the FDA is currently considering Alere's application in the U.S.

In the newly published study, the researchers examined the accuracy of plasma NGAL as a marker of AKI in patients with urgent health issues presenting to the ED.

     The study included 616 patients who presented to the ED of Fernando Fonseca Hospital and were admitted for treatment from March to November of 2008. Baseline renal function by SCr, medical history and demographic characteristics were obtained from hospital electronic records.

     Prospective renal function assessment was carried out by measuring SCr, serum cystatin C (SCysC), and plasma NGAL at 0, 6, 12, 24, and 48 hours from hospital admission.

     Plasma NGAL levels among patients with AKI remained significantly higher than in patients with normal kidney function for all time points  P menor a 0.001. When the combined group of AKI plus transient kidney injury patients was examined, the values of plasma NGAL remained significantly different from patients with normal kidney function P menor a 0.001 for all time points and the test was able to differentiate AKI from transient injury P menor a 0.001 for all time points.

Among the other findings:

·         Higher levels of plasma NGAL were associated with more severe AKI using AKI Network classification (median values ranging between 69 and 75, 125.5 and 148, 168 and 195, and 301.5 and 328.5 ng/ml for AKI Network stages 0,1,2, and 3, respectively.

·         ROC curves were generated to assess the discriminative ability of the NGAL test for diagnosing AKI. The area under the curves (AUCs) for AKI prediction were 0.77, 0.81, 0.82, 0.79 and 0.78 at 0, 6, 12, 24, and 48 hours, respectively. The AUC for discriminating between patients with AKI and those with normal kidney function was 0.85 (95% CI, 0.81-0.90) at the 12-hour time point.

·         The addition of plasma NGAL to the clinical model yielded a net reclassification improvement of 94.3% and an integrated discrimination improvement of 0.122.

·         When patients were classified into three grades of risk according to plasma NGAL levels  menor de 97 ng/ml was considered low risk and mayor que 133 ng/ml was considered high risk), those in the high risk category were found to have a 10-fold greater risk of AKI  odds ratio, 9.8; 95% CI, 5.6-16.9.

"When pNGAL concentrations are in the gray zone  mayor que 97 ng/ml to menos de 133 ng/ml we propose the recognition of risk factors that are independent predictors of AKI, including age, chronic kidney disease and comorbidities like cardiovascular disease," the researchers wrote. "Thus, patients with these risk factors may be considered at high risk of AKI, even when plasma NGAL levels are in the gray zone."

Devarajan said the findings prove the test could improve the clinical management of patients suspected of having AKI in the emergency treatment setting.

"The incidence of AKI varies from 20% to 40% in critical care patients and it is a significant cause of death," he said. "This test could markedly increase our ability to discriminate between true, intrinsic AKI and other conditions."

Tomado de Medpagetoday.com

Herramientas moleculares mejoradas detectan virus de la influenza

Se han diseñado y evaluado un conjunto de análisis moleculares para las infecciones virales de influenza, que pueden producir resultados sin la necesidad de equipo adicional.

Los ensayos moleculares son sensibles y una buena alternativa para los métodos de diagnóstico convencionales, ya que permiten la detección cuantitativa y cualitativa del virus de la gripe y las mutaciones de resistencia a los medicamentos.

Científicos de la Universidad Erasmus (Rotterdam, Holandal) diseñaron, validaron y evaluaron un conjunto de análisis de reacción en cadena de la polimerasa en tiempo real (RT-PCR) para la cuantificación y la determinación de los subtipos del virus de la influenza humana A y B a partir del material respiratorio del paciente, así como cuatro ensayos para la detección de mutaciones de resistencia a los medicamentos.

El equipo científico analizó 245 muestras respiratorias de 87 pacientes que viven en Asia, Europa y los Estados Unidos de América, que se inscribieron en un estudio prospectivo de la gripe, incluyendo la evaluación de la resistencia a la neuraminidasa. Además, se analizaron 96 virus pre-pandémicos H1N1 de la epidemia de 2007 a 2008, mediante el ensayo de H275Y para comprobar lo robusto del análisis.

El análisis de cuantificación de la gripe se utiliza para comprobar la positividad del virus y obtener el recuento de partículas de virus en todas las muestras analizadas. Posteriormente se determinó el subtipo de los virus de influenza y se analizaron para detectar la presencia de mutaciones de resistencia al oseltamivir utilizando los ensayos de RT-PCR de resistencia. En total, 129 muestras respiratorias dieron positivo para la influenza A y 60 para el virus de la gripe B. Una de las muestras dio positiva para los dos tipos de virus.

La infección por H7N9, la nueva cepa potencial pandémica de influenza o H5N1, una amenaza pandémica continua desde 1997, se pueden identificar por exclusión con un resultado positivo en la matriz de influenza RT-PCR, pero negativa en la tipificación con RT-PCR. El desarrollo de la tipificación rápida de RT-PCR para estos virus potenciales pandémicos puede ser útil en la complementación del conjunto existente. En un día de trabajo, se puede obtener información en paralela con respecto al virus o subtipo de virus de la influenza, la carga viral, y la susceptibilidad antiviral.

Martin Schutten, PhD, el autor principal del estudio, dijo: “Los análisis basados en RT-PCR se han convertido en la norma en la mayoría de los laboratorios de diagnóstico en todo el mundo, en los últimos años. Nuestros ensayos cubren todos los virus de la gripe humana que circulan actualmente y pueden detectar las principales mutaciones de resistencia al oseltamivir. Mediante la introducción de cuantificación externa y estándares internos, el desempeño del ensayo longitudinal puede ser seguido cuidadosamente y se puede asignar un recuento de partículas del virus a una muestra analizada”.

Tomado de labmedica.es

APRENDIZAJE BASADO EN UN CASO

A 59-year-old man with a history of heavy alcohol use presented to the emergency department for evaluation of abdominal swelling and abdominal discomfort. He also reported scleral icterus, which had developed over the prior two days, and denied recent fever, chills, hematemesis, melena, chest pain, shortness of breath, or change in bowel habits. He drank six twelve-ounce beers daily for the past 30 years and denied any history of intravenous drug abuse, acetaminophen use, homemade tattoos, or blood transfusions. He was taking no prescribed medications.

Vital signs upon presentation included a temperature of 99.7˚ Fahrenheit, pulse of 145 beats per minute, blood pressure of 123/89 mmHg, and a respiratory rate of 13 breaths per minute. Pertinent physical findings included drowsiness, scleral icterus, and tachycardia. His abdominal exam revealed a distended, nontender abdomen with normoactive bowel sounds. The liver measured 12 cm in the right midclavicular line, and no spleen tip was palpated. Pitting edema was present in his lower extremities. His neurological exam demonstrated asterixis, and skin examination revealed spider angiomas over his chest wall but no evidence of palmar erythema or tattoos.

His admission laboratory values revealed a 
Serum sodium of 134 mmol/L (135-146 mmol/L) 
Potassium of 3.0 mmol/L (3.6-5.2mmol/L) 
Chloride of 94 mmol/L (96- 110mmol/L) 
Creatinine of 0.8 mg/dL (0.8-1.5 mg/dL)
Blood urea nitrogen of 5 (7-25 mg/dl)
Glucose of 126 mg/dL(65-99 mg/dL) 
Total protein of 6.8 gm/dL (6-8 gm/dL) 
Albumin of 2.4 gm/dL (3.4-5.4 gm/dL)
Total bilirubin of 7.0 mg/dL (menos de 1 mg/dL)
AST of 102 U/L (menos de 45 U/L)
ALT 40 U/L (menos de 46 U/L)
Alkaline phosphatase of 235 U/L (20-120 U/L), 
Nonreactive acute hepatitis panel, and an ammonia level of 71 μmol/L (9-35 μmol/L). 
His white blood cell count was 6.8x103/μL (4.5-11x103/μL); platelet count of 107x103/μL (130-400x103/μL), and a hemoglobin and hematocrit of 13.4 gm/dL (13.5-17.5 gm/dL) and 38.7 percent (40-51 percent), respectively, were reported.


Comenta el caso indicando conducta a seguir y diagnostico diferencial.

APRENDIZAJE BASADO EN PROBLEMAS

The patient is a 39-year-old Caucasian male who at age 30 had a left anterior myocardial infarction. Shortly thereafter the patient experienced his first of several strokes. Residual deficits include memory loss and expressive aphasia. Multiple neurologic and cardiac imaging studies have failed to demonstrate an etiology. Laboratory findings have repeatedly demonstrated a prolonged activated partial throm-boplastin time and borderline thrombocytopenia. The initial laboratory findings are 
TTP  53.5 seg  (25-35)
TP    12.9 seg  (11-13)
1.-What is the Laboratory test-based algorithm in this case

Cometa el caso con diagnostico probable y diagnostico diferencial