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BACKGROUND: Acute kidney injury (AKI) is a common complication in patients admitted to intensive care unit (ICU) and mortality rates for this condition are high. To reduce the high incidence of short-term mortality, reliable prognostic indicators are required to facilitate early diagnosis and treatment of AKI. We assessed the ability of plasma proenkephalin (pPENK) and plasma neutrophil gelatinase-associated lipocalin (pNGAL) to predict 28-day mortality in AKI patients in intensive care. METHODS: This prospective study, carried out between January 2019 and December 2019, comprised 150 patients (100 male) diagnosed with AKI after excluding 20 patients discharged within 24 h and those with missing hospitalization data. Blood samples were collected to determine admission p-PENK and p-NGAL levels. The study outcome was 28day mortality. RESULTS: The mean patient age was 68 years (female, 33%). The average PPENK and pNGAL levels were 0.24 ng/µL and 223.70 ng/mL, respectively. PPENK levels >0.36 ng/µL and pNGAL levels >230.30 ng/mL were used as critical values to reliably indicate 28day mortality for patients with AKI (adjusted hazard ratios 0.785 [95% confidence interval 0.706-0.865, P<0.001] and 0.700 [95% confidence interval 0.611-0.789, P<0.001], respectively). This association was significant for mortality in patients in intensive care with AKI. Baseline p-PENK (0.36 ng/µL) and p-NGAL (230.30 ng/mL) levels and their respective cut-off values showed clinical value in predicting 28-day mortality. CONCLUSION: Serum PENK and NGAL levels, when used in conjunction, improved the accuracy of predicting 28-day mortality in patients with AKI while retaining sensitivity and specificity.
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Lesión Renal Aguda , Biomarcadores , Encefalinas , Unidades de Cuidados Intensivos , Lipocalina 2 , Humanos , Lesión Renal Aguda/sangre , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/diagnóstico , Masculino , Femenino , Lipocalina 2/sangre , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Encefalinas/sangre , Biomarcadores/sangre , Precursores de Proteínas/sangre , Pronóstico , Valor Predictivo de las Pruebas , Anciano de 80 o más Años , Mortalidad HospitalariaRESUMEN
OBJECTIVES: Consensus regarding biomarkers for detection of infection-related organ dysfunction in the emergency department is lacking. We aimed to identify and validate biomarkers that could improve risk prediction for overt or incipient organ dysfunction when added to quick Sepsis-related Organ Failure Assessment (qSOFA) as a screening tool. DESIGN: In a large prospective multicenter cohort of adult patients presenting to the emergency department with a qSOFA score greater than or equal to 1, admission plasma levels of C-reactive protein, procalcitonin, adrenomedullin (either bioavailable adrenomedullin or midregional fragment of proadrenomedullin), proenkephalin, and dipeptidyl peptidase 3 were assessed. Least absolute shrinkage and selection operator regression was applied to assess the impact of these biomarkers alone or in combination to detect the primary endpoint of prediction of sepsis within 96 hours of admission. SETTING: Three tertiary emergency departments at German University Hospitals (Jena University Hospital and two sites of the Charité University Hospital, Berlin). PATIENTS: One thousand four hundred seventy-seven adult patients presenting with suspected organ dysfunction based on qSOFA score greater than or equal to 1. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort was of moderate severity with 81% presenting with qSOFA = 1; 29.2% of these patients developed sepsis. Procalcitonin outperformed all other biomarkers regarding the primary endpoint (area under the curve for receiver operating characteristic [AUC-ROC], 0.86 [0.79-0.93]). Adding other biomarkers failed to further improve the AUC-ROC for the primary endpoint; however, they improved the model regarding several secondary endpoints, such as mortality, need for vasopressors, or dialysis. Addition of procalcitonin with a cutoff level of 0.25 ng/mL improved net (re)classification by 35.2% compared with qSOFA alone, with positive and negative predictive values of 60.7% and 88.7%, respectively. CONCLUSIONS: Biomarkers of infection and organ dysfunction, most notably procalcitonin, substantially improve early prediction of sepsis with added value to qSOFA alone as a simple screening tool on emergency department admission.
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Biomarcadores , Servicio de Urgencia en Hospital , Puntuaciones en la Disfunción de Órganos , Polipéptido alfa Relacionado con Calcitonina , Sepsis , Humanos , Sepsis/diagnóstico , Sepsis/sangre , Biomarcadores/sangre , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Polipéptido alfa Relacionado con Calcitonina/sangre , Adrenomedulina/sangre , Insuficiencia Multiorgánica/diagnóstico , Insuficiencia Multiorgánica/sangre , Insuficiencia Multiorgánica/etiología , Proteína C-Reactiva/análisis , Adulto , Encefalinas/sangre , Precursores de ProteínasAsunto(s)
Lesión Renal Aguda , Biomarcadores , Procedimientos Endovasculares , Encefalinas , Precursores de Proteínas , Humanos , Biomarcadores/sangre , Estudios Transversales , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/sangre , Procedimientos Endovasculares/efectos adversos , Masculino , Encefalinas/sangre , Anciano , Femenino , Precursores de Proteínas/sangre , Persona de Mediana Edad , Implantación de Prótesis Vascular/efectos adversos , Fragmentos de Péptidos/sangre , Reparación Endovascular de AneurismasRESUMEN
OBJECTIVES: Accurate determination of glomerular filtration rate (GFR) is important. Several endogenous biomarkers exist for estimating GFR, yet, they have limited accuracy, especially in the paediatric population. Proenkephalin A 119-159 (PENK) is a novel and promising GFR marker, but its relation with age in children remains unknown. Also, the value of PENK has never been validated against measured GFR (mGFR) in children when compared to traditional GFR markers including serum creatinine (SCr), SCr-based estimated GFR (eGFR) and cystatin C (cysC). METHODS: Critically ill children and term-born neonates were included in this single-centre, prospective study. Iohexol-based mGFR, SCr, and cysC were determined in each patient. eGFR was calculated using the bedside Schwartz equation, incorporating SCr and height. Spearman correlation coefficients were calculated to determine the correlation between mGFR and PENK, SCr, cysC and eGFR. RESULTS: For 97 patients (56 children and 41 neonates), mGFR, SCr, cysC and PENK levels were available. PENK levels were higher in young children and decreased to adult PENK reference values around two years of age. PENK levels were highly correlated with mGFR (ρ=-0.88, p<0.001), and similar to mGFR-eGFR correlation (ρ=-0.87, p<0.001). For cysC and SCr the correlation with mGFR was lower (ρ=-0.77 and ρ=-0.46, respectively. Both p<0.001). CONCLUSIONS: The correlation of PENK with mGFR was as good as SCr-based eGFR-mGFR correlation. To determine the added value of PENK in paediatric clinical care and prior to implementation, PENK reference values are needed and the development and validation of a paediatric PENK-based eGFR equation is necessary.
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Enfermedad Crítica , Encefalinas , Tasa de Filtración Glomerular , Yohexol , Niño , Preescolar , Humanos , Recién Nacido , Biomarcadores , Creatinina , Estudios Prospectivos , Encefalinas/sangreRESUMEN
Background and Objectives: In order to accelerate the risk stratification of patients referred to the Emergency Department (ED) with interstitial pneumonia, it could be useful to provide new and effective laboratory tests for use. The aim of our study was to evaluate the prognostic role of two biomarkers, bio-adrenomedullin (Bio-ADM) and proenkephalin (penKid), in patients with interstitial pneumonia (IP) at ED admission. Materials and Methods: In 153 consecutive patients with IP, both from COVID-19 or non-COVID-19 etiology, we measured, in a prospective observational manner, penKid and Bio-ADM at ED admission and after 24 h. In order to evaluate patient outcomes, 30-day follow-ups were also performed. The endpoints were 24 h, 10-day, and 30-day mortality. Results: Both biomarkers were shown to be good predictors of adverse events at 30 days, with Bio-ADM outperforming penKid. Bio-ADM was linked with 24 h and 10-day patient mortality. Moreover, PenKid was related to parameters defining worsening kidney function. Conclusions: Both in patients with COVID-19 or non-COVID-19 interstitial pneumonia at ED admission, Bio-ADM and penKid were good predictors of patient mortality. To evaluate these two biomarkers could be considered to be useful during the first evaluation in the ED when integrated with clinical scores.
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Adrenomedulina , COVID-19 , Encefalinas , Enfermedades Pulmonares Intersticiales , Humanos , Adrenomedulina/sangre , Biomarcadores , COVID-19/mortalidad , Servicio de Urgencia en Hospital , Pronóstico , Encefalinas/sangre , Enfermedades Pulmonares Intersticiales/mortalidadRESUMEN
OBJECTIVES: The opioid neuropeptide pro-enkephalin A (PENK-A) may be a circulating marker of cardiovascular risk, with prior findings relevant to heart failure, kidney disease, and vascular dementia. Despite these findings, the association of PENK-A with ischemic stroke is unknown, so we examined this association in a prospective cohort study and analyzed differences by race and sex. MATERIALS AND METHODS: The REasons for Geographic and Racial Differences in Stroke study (REGARDS) is a prospective cohort study of 30,239 Black and White adults. Plasma PENK-A was measured in 473 participants that developed first-time ischemic stroke over 5.9 years and 899 randomly selected participants. Cox models adjusted for demographics and stroke risk factors were used to calculate hazard ratios (HRs) of stroke by baseline PENK-A. RESULTS: PENK-A was higher with increasing age, female sex, White race, lower body mass index, and antihypertensive medication use. Each SD higher increment of PENK-A was associated with an adjusted HR of 1.20 (95% CI 1.01-1.42) for stroke, with minimal confounding by stroke risk factors. Spline plots suggested a U-shaped relationship, particularly in White men, with an adjusted HR 3.88 (95% CI 1.94-7.77) for the 95th versus 50th percentile of PENK-A in White men. CONCLUSIONS: Higher baseline plasma PENK-A was independently associated with future stroke risk in REGARDS. This association was most apparent among White men. There was little confounding by established stroke risk factors, suggesting a possible causal role in stroke etiology. Further research is needed to understand the role of endogenous opioids in stroke pathogenesis.
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Encefalinas , Disparidades en el Estado de Salud , Accidente Cerebrovascular Isquémico , Precursores de Proteínas , Adulto , Biomarcadores/sangre , Población Negra/estadística & datos numéricos , Encefalinas/sangre , Femenino , Geografía , Humanos , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/etnología , Masculino , Estudios Prospectivos , Precursores de Proteínas/sangre , Factores Raciales , Factores de Riesgo , Población Blanca/estadística & datos numéricosRESUMEN
Aim of the study is to compare prodynorphin (PDYN) rs1997794, rs1022563, rs6045819, rs2235749 polymorphisms in individuals with methamphetamine use disorder (MD) to that of healthy controls (HC), and to investigate the differences in serum PDYN levels in methamphetamine withdrawal. It is also aimed to explore the temperament characteristics and depression and their relationship with PDYN polymorphisms and PDYN serum levels in MD group. PDYN gene and serum levels were studied in 134 patients with MD and 97 HC. Patients with MD were administered Beck Depression Inventory (BDI) and Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A). For rs1022563 polymorphism, TT and CT genotype frequency and T allele frequency were significantly higher in the MD group than the frequencies in HC. It was found that rs2235749 polymorphism AA genotype was associated with increased risk of MD. PDYN rs1997794 CT genotypes had significantly higher scores of TEMPS-A irritable than CC genotypes and PDYN rs1022563 CC genotypes had significantly higher scores of TEMPS-A irritable than TT genotypes. PDYN levels among persons with MD were significantly higher than among the HC group when the withdrawal level increased and withdrawal symptoms improved. During the period in which the withdrawal level increased, there was a negative correlation between PDYN level and BDI and a positive relationship between PDYN level and TEMPS-A hyperthymic. It may be beneficial to screen temperament characteristics associated with increased risk of addiction in patients with MD and develop interventions based on temperament characteristics and the effects of PDYN.
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Encefalinas/genética , Metanfetamina , Precursores de Proteínas/genética , Trastornos Relacionados con Sustancias/genética , Depresión/genética , Encefalinas/sangre , Encefalinas/metabolismo , Humanos , Inventario de Personalidad , Polimorfismo Genético , Precursores de Proteínas/sangre , Precursores de Proteínas/metabolismo , Psicometría , Encuestas y Cuestionarios , Temperamento , TurquíaRESUMEN
Iraqi-born immigrants residing in Sweden exhibit lower blood pressure as well as better renal function despite an overall worse metabolic risk profile in comparison with native Swedes. This may indicate the presence of cardiorenal protective mechanisms in the Middle Eastern population. Hence, the aim of this study was to investigate whether the association between renal function and Pro-Enkephalin (PENK), a biomarker predictive of both acute and chronic kidney dysfunction, differs across ethnicities. The MEDIM population-based study including a cohort of women and men, born in Iraq or Sweden, aged 30-75 years was conducted in Malmö, Sweden, from 2010 to 2012. The study included fasting blood samples, physical examinations and self-administrated questionnaires. Despite significantly better renal function assessed by creatinine-based eGFR in the Iraqi group, levels of PENK did not differ between the groups, (70.0 pmol/L, born in Iraq (n = 1263) vs 71.1, born in Sweden (n = 689), p = .4). However, the association between PENK and renal function was relatively weaker in the Iraqi born group, as supported by a significant interaction between PENK and country of birth (PInteraction= Country of birth x PENK = 0,010). This observational study suggests that the association between renal function and PENK was weaker in Middle Eastern immigrants. This is of interest as PENK may exhibit a direct effect on renal function, however further research is needed including studies on causality.
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Emigrantes e Inmigrantes , Encefalinas/sangre , Pruebas de Función Renal , Riñón/fisiopatología , Precursores de Proteínas/sangre , Adulto , Anciano , Presión Sanguínea/fisiología , Etnicidad , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Masculino , Persona de Mediana Edad , Medio Oriente , Caracteres Sexuales , SueciaRESUMEN
Assessment of kidney function is primarily based on urine output and Creatinine (Cr)-based methods to estimate glomerular filtration rate (GFR). The latter is confounded as Cr is not exclusively filtered by the kidney and rises relatively late after the onset of acute kidney injury (AKI). This leads to delays in recognition of reduced kidney function and diagnosis of AKI, particularly in critically ill patients where kidney function can change rapidly. The gold standard methods of GFR determination, such as inulin or iohexol clearance, are labor intensive and unfeasible in acute clinical settings. Proenkephalin A 119-159 (PENK) has been intensively studied as a novel biomarker of kidney function. PENK belongs to the enkephalin peptide family and is freely filtrated in the glomerulus. Plasma PENK concentration appears to correlate strongly with GFR. Moreover, increased plasma PENK concentrations are found to be associated with long-term kidney outcomes and mortality. In this review, we summarize the role of PENK in assessment of kidney function and its capacity to predict various clinical outcomes.
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Lesión Renal Aguda/sangre , Encefalinas/sangre , Tasa de Filtración Glomerular , Precursores de Proteínas/sangre , Lesión Renal Aguda/fisiopatología , Biomarcadores/sangre , Enfermedad Crítica , Humanos , Riñón/fisiopatologíaAsunto(s)
Lesión Renal Aguda/etiología , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Torácica/cirugía , Procedimientos Endovasculares/efectos adversos , Encefalinas/sangre , Fragmentos de Péptidos/sangre , Precursores de Proteínas/sangre , Procedimientos Quirúrgicos Vasculares/efectos adversos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/mortalidad , Anciano , Aneurisma de la Aorta Abdominal/sangre , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/mortalidad , Aneurisma de la Aorta Torácica/sangre , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/mortalidad , Procedimientos Endovasculares/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/mortalidadRESUMEN
Objectives Acute kidney injury (AKI) is common in critically ill children, but current biomarkers are suboptimal. Proenkephalin A 119-159 (PENK) is a promising new biomarker for AKI in adults, but pediatric data is lacking. We determined PENK reference intervals for healthy children, crucial for clinical implementation, and explored concentrations in critically ill infants aged under 1 year. Methods Observational cohort study in healthy infants and critically ill children aged 0-1 years. Reference values were determined using generalized additive models. Plasma PENK concentrations between healthy children and critically ill children with and without AKI, were compared using linear mixed modelling. The performance of PENK as AKI biomarker was compared to cystatin C (CysC) and ß-trace protein (BTP) using receiver-operating-characteristic (ROC) analysis. Results PENK concentrations in 100 healthy infants were stable during the first year of life (median 517.3 pmol/L). Median PENK concentrations in 91 critically ill children, were significantly higher in those with AKI (n=40) (KDIGO Stage 1 507.9 pmol/L, Stage 2 704.0 pmol/L, Stage 3 930.5 pmol/L) than non-AKI patients (n=51, 432.2 pmol/L) (p < 0.001). PENK appeared to relate better to AKI diagnosis than CysC and BTP (AUROC PENK 0.858, CysC 0.770 and BTP 0.711) in the first 24 h after recruitment. Conclusions PENK reference values are much higher in young infants than adults, but clearly discriminate between children with and without AKI, with comparable or better performance than CysC and BTP. Our results illustrate the importance of establishing age-normalized reference values and indicate PENK as a promising pediatric AKI biomarker.
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Lesión Renal Aguda/diagnóstico , Encefalinas/sangre , Fragmentos de Péptidos/sangre , Precursores de Proteínas/sangre , Lesión Renal Aguda/sangre , Área Bajo la Curva , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Humanos , Inmunoensayo/estadística & datos numéricos , Lactante , Recién Nacido , Masculino , Curva ROC , Valores de ReferenciaRESUMEN
Because environmental elements modify chronic pain development and endogenous mechanisms of pain control are still a great therapeutic source, we investigated the effects of an early exposure to environmental enrichment (EE) in a translational model of neuropathic pain. Young male rats born and bred in an enriched environment, which did not count on running wheel, underwent chronic constriction injury (CCI) of sciatic nerve. EE abolished neuropathic pain behavior 14 days after CCI. Opioid receptors' antagonism reversed EE-analgesic effect. ß-endorphin and met-enkephalin serum levels were increased only in EE-CCI group. Blockade of glucocorticoid receptors did not alter EE-analgesic effect, although corticosterone circulating levels were increased in EE animals. In the spinal cord, EE controlled CCI-induced serotonin increase. In DRG, EE blunted the expression of ATF-3 after CCI. Surprisingly, EE-CCI group showed a remarkable preservation of sciatic nerve fibers compared to NE-CCI group. This work demonstrated global effects induced by an EE protocol that explain, in part, the protective role of EE upon chronic noxious stimulation, reinforcing the importance of endogenous mechanisms in the prevention of chronic pain development.
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Ambiente , Neuralgia/prevención & control , Traumatismos de los Nervios Periféricos/complicaciones , Nervio Ciático/lesiones , Animales , Supervivencia Celular , Constricción Patológica , Endorfinas/sangre , Encefalinas/sangre , Hiperalgesia/patología , Masculino , Fibras Nerviosas/patología , Neuralgia/etiología , Neuralgia/patología , Traumatismos de los Nervios Periféricos/patología , Ratas , Ratas Wistar , Receptores de Glucocorticoides/metabolismo , Nervio Ciático/patología , Médula Espinal/metabolismo , Soporte de PesoRESUMEN
Rationale: Subclinical acute kidney injury (sub-AKI) refers to patients with low serum creatinine but elevated alternative biomarkers of AKI. Its incidence and outcome in critically ill patients remain, however, largely unknown. Plasma proenkephalin A 119-159 (penKid) has been proposed as a sensitive biomarker of glomerular function.Objectives: In this ancillary study of two cohorts, we explored the incidence and outcome of sub-AKI based on penKid.Methods: A prospective observational study in ICUs was conducted. FROG-ICU (French and European Outcome Registry in ICUs) enrolled 2,087 critically ill patients, and AdrenOSS-1 (Adrenomedullin and Outcome in Severe Sepsis and Septic Shock-1) enrolled 583 septic patients. The primary endpoint was 28-day mortality after ICU admission. Sub-AKI was defined by an admission penKid concentration above the normal range (i.e., >80 pmol/L) in patients not meeting the definition of AKI. A sensitivity analysis was performed among patients with estimated glomerular filtration rate above 60 ml/min/1.73 m2 at ICU admission.Measurements and Main Results: In total, 6.1% (122/2,004) and 6.7% (39/583) of patients from the FROG-ICU and AdrenOSS-1 cohorts met the definition of sub-AKI (11.6% and 17.5% of patients without AKI). In patients without AKI or with high estimated glomerular filtration rate, penKid was associated with higher mortality (adjusted standardized hazard ratio [HR], 1.4 [95% confidence interval, 1.1-1.8]; P = 0.010; and HR, 1.6 [95% confidence interval, 1.3-1.8]; P < 0.0001, respectively) after adjustment for age, sex, comorbidities, diagnosis, creatinine, diuresis, and study. Patients with sub-AKI had higher mortality compared with no AKI (HR, 2.4 [95% confidence interval, 1.5-3.7] in FROG-ICU and 2.5 [95% confidence interval, 1.1-5.9] in AdrenOSS-1).Conclusions: Sub-AKI defined using penKid occurred in 11.6-17.5% of patients without AKI and was associated with a risk of death close to patients with AKI.
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Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/mortalidad , Biomarcadores/sangre , Enfermedad Crítica/terapia , Encefalinas/sangre , Precursores de Proteínas/sangre , Lesión Renal Aguda/epidemiología , Anciano , Estudios de Cohortes , Toma de Decisiones , Europa (Continente)/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Kidney failure occurs frequently and is associated with high mortality during sepsis. Proenkephalin (PENK) is an emerging biomarker of kidney function. We explored whether PENK levels could predict severity, organ failure, and mortality in septic patients. METHODS: We measured the PENK level in the plasma of 215 septic patients using the sphingotest penKid assay (Sphingotec GmbH, Hennigsdorf, Germany). This was analyzed in terms of sepsis severity, vasopressor use, 30-day mortality, sequential organ failure assessment (SOFA) renal subscore, the Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (CKD-EPI eGFR) categories, and renal replacement therapy (RRT) requirement. RESULTS: The PENK levels were significantly higher in patients with septic shock, vasopressor use, and non-survivors than in patients with solitary sepsis, no vasopressor use, and survivors, respectively (P=0.02, P=0.007, P<0.001, respectively). The PENK levels were significantly associated with SOFA renal subscore and CKD-EPI eGFR categories (both P<0.001). The distribution of lower eGFR (<60 mL/min/1.73 m2), RRT requirement, SOFA renal subscore, and the number of organ failures differed significantly according to the PENK quartile (P for trend<0.001 or 0.017). The 30-day mortality rate also differed significantly according to the PENK quartile (P for trend<0.001). CONCLUSIONS: PENK could be an objective and reliable marker to predict severity, organ failure, and 30-day mortality in septic patients.
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Encefalinas/sangre , Insuficiencia Multiorgánica/patología , Precursores de Proteínas/sangre , Insuficiencia Renal Crónica/patología , Sepsis/patología , Anciano , Biomarcadores/sangre , Femenino , Tasa de Filtración Glomerular , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/complicaciones , Modelos de Riesgos Proporcionales , Juego de Reactivos para Diagnóstico , Insuficiencia Renal Crónica/complicaciones , Sepsis/mortalidad , Choque Séptico/complicaciones , Choque Séptico/mortalidad , Choque Séptico/patologíaRESUMEN
Midregional Pro-enkephalin A (MR-PENK A) and N-terminal Protachykinin A (NT-PTA) have been associated with vascular dementia. However, the longitudinal relationship between these biomarkers and incident dementia has not been fully investigated. In the population-based Malmö Preventive Project, circulating levels of MR-PENK A and NT-PTA were determined in a random sample of 5,323 study participants (mean age: 69 ± 6 years) who were followed-up over a period of 4.6 ± 1.6 years. The study sample included 369 patients (7%) who were diagnosed in the same period with dementia. We analyzed relationship of MR-PENK A and NT-PTA with the risk of developing dementia by using multivariable-adjusted Cox regression models adjusted for traditional risk factors. Increased plasma levels of MR-PENK A were associated with higher risk of incident vascular dementia whereas no associations were found with all-cause or Alzheimer dementia. The risk of vascular dementia was mainly conferred by the highest quartile of MR-PENK as compared with lower quartiles. Elevated levels of NT-PTA yielded significant association with all-cause dementia or dementia subtypes. Elevated plasma concentration of MR-PENK A independently predicts vascular dementia in the general population. MR-PENK A may be used as an additional tool for identifying vascular subtype in ambiguous dementia cases.
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Demencia Vascular/sangre , Demencia Vascular/epidemiología , Encefalinas/sangre , Precursores de Proteínas/sangre , Anciano , Biomarcadores , Demencia Vascular/diagnóstico , Demencia Vascular/etiología , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Pronóstico , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Suecia/epidemiologíaRESUMEN
BACKGROUND: Proenkephalin A 119-159 (penKid) has been proposed as a sensitive biomarker of renal function. This study evaluated the association of concentrations of plasma penKid with death and risk of acute kidney injury (AKI) in severely ill burn patients. METHODS: A prospective observational study in two centers with severely ill adult burn patients was conducted. The inclusion criteria were total body surface area (TBSA) burns >15%, with burn injury occurring <72 h before intensive care unit (ICU) admission and plasma sample taken at admission. The primary endpoint was 90-day mortality. The secondary endpoints were AKI and a combined endpoint of 90-day mortality and/or AKI. Mortality was also evaluated in the sub-group of patients with sub-clinical AKI, defined as a patient without AKI but with elevated penKid. RESULTS: A total of 113 consecutive patients were enrolled. The median age was 48 years (Interquartile range [IQR] 33-64), the median burn TBSA was 35% (IQR 25-53), and 90-day mortality was 31.9%. Thirty-one percent of the patients had AKI, and 41.6% of patients had the combined endpoint. There was a stepwise decrease in survival from patients without AKI, sub-AKI, and with AKI (survival rate 90.0% [95% CI 82.7-97.9], 66.7% [95% CI 48.1-92.4], and 31.4% [95% CI 19.3-51.3], respectively, p < 0.001). Plasma penKid concentration was significantly higher in non-survivors compared to survivors (86.9 pmol/L [IQR 53.3-166.1] versus 52.9 pmol/L [IQR 37.1-70.7]; p = 0.0001) and in patients with AKI compared to patients without AKI (86.4 pmol/L [IQR 56.5-153.4] versus 52.5 pmol/L [IQR 35.5-71.2]; p < 0.001). Penkid provided added value on top of serum creatinine (Screat) and Sepsis Related Organ Failure Assessment (SOFA) scores to predict 90-day mortality (combined c-index of 0.738 versus 0.707; p = 0.024 and 0.787 versus 0.752; p < 0.001). CONCLUSIONS: Plasma penKid concentration at admission was associated with an increased risk of death in burn patients. PenKid has additional prognostic value on top of Screat and SOFA to predict 90-day mortality.
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Lesión Renal Aguda/epidemiología , Quemaduras/sangre , Encefalinas/sangre , Mortalidad , Fragmentos de Péptidos/sangre , Precursores de Proteínas/sangre , Lesión Renal Aguda/sangre , Lesión Renal Aguda/terapia , Adulto , Anciano , Biomarcadores/sangre , Superficie Corporal , Creatinina/sangre , Femenino , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Estudios Prospectivos , Terapia de Reemplazo RenalRESUMEN
OBJECTIVE: The aim of this study was to confirm previous observations that proenkephalin A (PENK-A) may serve as prognostic marker in the setting of acute ischemic stroke in a large stroke cohort. METHODS: The plasma concentration of PENK-A was measured within 72 hours of symptom onset in 320 consecutively enrolled patients with stroke. The primary outcome measures were unfavorable functional outcome (modified Rankin Scale score 0-2 vs 3-6) and mortality within 90 days. Logistic and cox proportional regression analyses were fitted to estimate odds ratios (ORs), hazard ratios (HRs) and 95% confidence intervals (CIs), respectively, for the association between PENK-A and the primary outcome measures. RESULTS: After adjusting for demographic and vascular risk factors, PENK-A was neither independently associated with functional outcome (OR: 1.29, 95% CI: 0.16-10.35) nor mortality (HR: 1.02, 95% CI: 0.14-7.33). CONCLUSION: Among patients with acute stroke, PENK-A does not serve as an independent prognostic marker in this external validation cohort.
Asunto(s)
Encefalinas/sangre , Precursores de Proteínas/sangre , Accidente Cerebrovascular/diagnóstico , Anciano , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidad , Estudios de Cohortes , Humanos , Oportunidad Relativa , Pronóstico , Análisis de Regresión , Accidente Cerebrovascular/mortalidadRESUMEN
BACKGROUND: The assessment of renal function in clinical practice remains challenging. Using creatinine to assess the glomerular filtration rate (GFR) is notoriously inaccurate, and determination of the true GFR, e.g., using inulin or iohexol, is laborious and not feasible in daily practice. Proenkephalin (PENK) is a novel candidate biomarker for kidney function that is filtrated in the glomerulus, has shown to represent steady-state GFR in patients with different severities of renal insufficiency. In this pilot study in non-steady-state critically ill patients, we compared plasma PENK concentrations with creatinine-based GFR assessments and validated both against the "true GFR" measured using a gold standard method: iohexol plasma clearance. METHODS: Twenty-three critically ill patients with septic shock were included. Kidney function was determined using the Modification of Diet in Renal Disease formula (eGFRMDRD), Endogenous Creatinine Clearance (GFRECC), and iohexol plasma clearance (GFRiohexol) during a 6-h window. Plasma PENK concentrations were measured using the penKid immunoassay. RESULTS: The eGFRMDRD and GFRECC correlated with the GFRiohexol (Râ=â0.82, Pâ<â0.0001 and Râ=â0.82, Pâ<â0.0001 respectively); however, bias and variability were considerable: the eGFRMDRD overestimated the true GFR with 31â±â35% (95% limits of agreement: -37% to 100%) and the GFRECC with 37â±â49% (95% limits of agreement: -59% to 133%). Plasma PENK concentrations showed a very strong inverse correlation with the GFRiohexol (Râ=â0.90, Pâ<â0.0001) which tended to be better compared with the correlation of eGFRMDRD (Pâ=â0.06) and GFRECC (Pâ=â0.08) with the GFRiohexol. CONCLUSIONS: In this pilot study in non-steady-state critically ill sepsis patients, GFR appears to be more accurately reflected by plasma PENK concentrations compared to conventional creatinine-based methods. Therefore, PENK holds promise as an accurate and feasible biomarker to determine kidney function during non-steady-state conditions in the critically ill.
Asunto(s)
Encefalinas/sangre , Yohexol/farmacocinética , Precursores de Proteínas/sangre , Sepsis/sangre , Choque Séptico/sangre , Anciano , Enfermedad Crítica , Humanos , Inulina/sangre , Riñón/metabolismo , Pruebas de Función Renal , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Sepsis is a leading cause of death worldwide and a major challenge for physicians to predict and manage. Proenkephalin A 119-159 (penKid) is a reliable surrogate marker for the more unstable endogenous opioid peptide enkephalin, which has previously been shown to predict both acute and chronic kidney disease. The aim of this prospective observational study was to assess penKid as a predictor of acute kidney injury (AKI), multi-organ failure and mortality in sepsis among unselected sepsis patients presenting to the emergency department (ED). METHOD: We enrolled 644 patients consecutively during office-hours (6 AM-6 PM) between December 1, 2013 and February 1, 2015. Fifty-six patients were excluded due to incomplete data. We measured penKid in 588 adult patients (patients under 18 years of age were excluded) with sepsis (≥2SIRS criteria + suspected infection) upon admission to the ED at Skåne University Hospital, Malmö, Sweden. Logistic regression analysis was used to relate levels of penKid at presentation to AKI, multi-organ failure, 28-day mortality and progression of renal SOFA subscore. Odds ratios are presented as the number of standard deviations from the mean of log-transformed penKid. RESULTS: In age and sex adjusted models, penKid predicted AKI within 48 h and 7 days, but these associations were attenuated after additional adjustment for estimated creatinine-based glomerular filtration rate (eGFR). In models adjusted for age, sex and eGFR, penKid significantly predicted progression from rSOFA = 0 and ≤ 1 to higher rSOFA scores as well as multi-organ failure and mortality. In contrast, eGFR did not predict 28-day mortality. CONCLUSION: PenKid is an effective predictor of renal injury, severe multi-organ failure and mortality in unselected sepsis patients presenting to the emergency department.