Urinary exosomes as a source of kidney dysfunction biomarker in renal transplantation.

End-stage renal disease (ESRD) requires for its treatment permanent dialysis or kidney transplantation (KT). KT is the best clinical treatment, however, the early function of the allograft varies depending on multiple factors associated with cold ischemia time (CIT) and the allograft rejection process. It is known that serum creatinine is an insensitive and late marker for predicting graft recovery after KT, mainly in patients with delayed graft function (DGF). Neutrophil gelatinase-associated lipocalin (NGAL) is produced in the distal nephron and it is one of the most promising novel biomarkers for acute kidney injury (AKI) and chronic kidney disease (CKD). NGAL has been proposed to be a predictor of organ recovery from DGF after KT from donors after cardiac death. Because nonrenal diseases can also induce NGAL, more information is necessary to validate the sensitivity and specificity of urine and plasma NGAL in clinical samples. The exosomes are vesicles released into the urine from the kidney epithelium and they have been proposed as better source to explore as biomarker of renal dysfunction. The molecular composition of the urinary exosomes could be representative of the physiological or physiopathologic condition of the urinary system. We propose that determination of NGAL in urinary exosomes is a better predictor of kidney dysfunction after KT than other urinary fractions. We analyzed 15 kidney allograft recipients, with a mean age of 36 years (range, 16-60 years) and 75% were male: 11 living donors (LD) and 4 deceased donors (DD). The average length of CIT was 14 hours in DD and less than 1 hour in LD. Three patient developed DGF. Using Western blot analysis, NGAL was detectable in the cellular and exosomal fraction of the urine. The exosomes expressed higher levels of NGAL than the cellular fraction. The expression of NGAL was observed from the first day after transplantation. In the cellular fraction of the urine, no significant differences of NGAL were observed between the patients. However, the median of NGAL expression in the exosomes fraction was significantly higher in DD patient, from the first day after KT (P < .05). Moreover, we noticed that NGAL expression in exosomes remained elevated in the patients with DGF compared with non-DGF patients (P < .05). Considering the highest abundance of NGAL in the urinary exosomes and its correlation with DGF patients, we suggest the exosomal fraction as a more sensitive substrate to evaluate early biomarkers of DGF after KT.

[Study of effectiveness of craving control with topiramate in patients with substance dependence disorders]. / Estudio de la efectividad del control del craving con topiramato en pacientes con trastornos por dependencia de sustancias.

INTRODUCTION: Effectiveness and tolerability of topiramate at 3 and 6 months was assessed in patients requesting dehabituation programs. METHODS: Observational, prospective, national and multicenter study of 6 months, in patients on treatment with topiramate, who fulfilled criteria for dependence of opiates according to ICD-10 participating in therapeutic programs of dehabituation, without concomitant psychiatric illnesses and any responsible relative. Main measures of effectiveness were retention rates, alcohol consumption and other illicit drugs by urine tests (opiates, cannabis, cocaine) and treatment needs by EuropASI scale. Other parameters were HAM-D, DAS-SV and SF-36. RESULTS: Patients with consumption by urine tests decreased from 94.1 % (n = 64) at baseline to 39.6 % (n = 19) after 6 months of treatment, as was seen by means of the mean score in EuropASI scale, for all substances except methadone. No consumption was accompanied by a low rate of relapse of 33.3 % at 6 months. Twenty one patients had adverse reactions (28 %). The most frequent adverse reactions were somnolence (n = 9; 12 %), paraesthesia (n = 5; 6.7 %) and depression (n = 4; 5.3 %). CONCLUSIONS: In real clinical practice, topiramate showed a good response with a relevant decrease of percent of patients with abuse or consumption, and a satisfactory tolerability profile for the treatment of patients with dependence on heroine, cocaine, and other opiates, showing better outcomes than those obtained in previous trials.

Estudio de la efectividad del control del craving con topiramato en pacientes con trastornos por dependencia de sustancias / Study of effectiveness of craving control with topiramate in patients with substance dependence disorders

Introducción. En la práctica clínica habitual se ha evaluado de eficacia y tolerabilidad d etopiramato a los 3 y 6 meses en pacientes que solicitaron programas de deshabituación. Métodos. Estudio observacional prospectivo, multicéntrico, topiramato, en pacientes con criterios de dependencia de opiáceos según la CIE-10 en programas terapéuticos de deshabituación, si otra patología psiquiátrica concomitante y con algún familiar responsable. Medidas principales de eficacia han sido: tasas de retención, consumo de alcohol y otras drogas de abuso en orina y necesidad de tratamiento del cuestionario EuropASI. Otros parámetros han sido las escalas HAM-D, DAS-SV y SF-36. Resultados. El número de pacientes consumidores según controles de orina descendió del 84,1% (n=64) basal al 39,6% (n=19) a los 6 meses de seguimiento, descenso que se reflejó también a partir de la puntuación media en el cuestionario EuropASI para todas las sustancias excepto la metadona. Esta alta tasa de no consumo se acompañó de una baja tasa de recaídas, del 33,3• a los 6 meses. Se registraron 21 pacientes con reacciones adversas (28%), siendo las reacciones adversas más frecuentes la somnolencia (n=9; 12%), las parestesias (n=5; 6,7%) y la depresión (n=4; 5,3%). Conclusiones. El topiramato mostró en condiciones asistenciales reales una buena respuesta, con una importante disminución del porcentaje de pacientes consumidores y un satisfactorio perfil de tolerabilidad en el tratamiento de pacientes con dependencia de heroína, cocaína y/u otros derivados opiáceos, mejorando los resultados obtenidos en ensayos clínicos previos (AU)

Introduction. Effectiveness and tolerability to topiramate at 3 and 6 months was assessed in patients requesting dehabituation programs. Methods. Observational, prospective, national and multicenter study of 6 months, in patients on treatment with topiramate, who fulfilled criteria for dependence of opiates according to ICD-10 participating in therapeutic programs of dehabituation, without concomitant psychiatric illnesses and any responsible relative. Main measures of dehabituation, without concomitant psychiatric illnesses and any responsible relative. Main measures of effectiveness were retention rates, alcohol consumption and other illicit drugs by urine test (opiates, cannabis, cocaine) and treatment needs by EuropASI scale, Other parameters were HAM-D, DAS-SV and SF-36. Results. Patients with consumptions by urine test decreased from 94.1% (n=64) at baseline to 39,6% (n=19) after 6 months of treatment, as was seen by means of the mean score in EuropASI scale, for all substances except methadone. No consumption was accompanied by a low rate of relapse of 33.3% at 6 months. Twenty one patients had adverse reactins (28%). The most frequent adverse reactions were somnolence (n=9, 13%), paraesthesia (n=5 6.7%) and depression (n=4; 5.3%). Conclusions. In real clinical practice, topiramate showed a good response with a relevant decrease of percent of patients with abuse or consumption, and a satisfactory tolerability profile for the treatment of patients with dependence on heroine, cocaine and other opiates, showing better outcome than those obtained in previous trials (AU)

Maintenance treatment with depot opioid antagonists in subcutaneous implants: an alternative in the treatment of opioid dependence.

A report is presented of treatment of 156 patients (male 98%) with opioid dependence (ICD-10 criteria) using a maintenance programme with depot opioid antagonists (naltrexone) as subcutaneous implants, started after an outpatient rapid antagonization regimen. The retention index in the treatment was from 80% in the sixth month, and 65% after one year. The patients were followed-up for 1 year after discharge. For 6 months after discharge 55.4% were still returning for follow-up visits and 20.8% after 1 year, all of them remaining abstinent to opioids. It is concluded that the programme is safe for the patients and shows a better retention index than programmes using oral antagonists, with an improved compliance (negative urine analysis) compared to the latter.

24-Hour opiate detoxification and antagonist induction at home--the 'Asturian method': a report on 1368 procedures.

The technique of domiciliary rapid opiate detoxification (ROD) developed in Asturias since 1994 enables patients dependent on heroin and/or methadone (or other opiates) to start antagonist maintenance with a full dose of naltrexone (50 mg) and largely recover from the acute opiate withdrawal syndrome in a few hours at home without direct medical or nursing involvement. Detailed information on 1368 procedures is presented but in Asturias, over 3000 procedures have been completed to date without any deaths or serious medical or psychiatric complications. We also describe some recent modifications to the procedure involving the use of octreotide as an antidiarrhoeal and the insertion of subcutaneous naltrexone implants to prevent early relapse. Rather than domiciliary ROD, we think the procedure is more usefully conceptualized as domiciliary rapid antagonist induction (RAI), because treatment with well-supervised naltrexone is known to be effective in reducing relapse rates. Now that controlled studies uniformly describe greatly increased rates of transfer to naltrexone maintenance treatment following RAI, compared with conventional slower withdrawal and naltrexone induction procedures, it is important that the safety, acceptability and simplicity of this 'Asturian' RAI/ROD technique become more widely known.

Moxonidina en las pautas de antagonización rápida ambulatoria en adictos a la heroína / Moxonidine in the outpatient rapid antagonization schedules in heroin addicts

Objetivo: Evaluar la efectividad de moxonidina en pautas de antagonización rápida ambulatoria (PARA). Pacientes y método: Veinte pacientes que solicitaron desintoxicación ambulatoria por consumo de opiáceos entre abril y octubre (1998). Dichos pacientes fueron asignados a dos grupos, según consumo de heroína: grupo A (< 250 mg/día), grupo B (250 mg/día). Ambos grupos fueron subdivididos en dos subgrupos en función del protocolo asignado: PARA con clonidina o PARA con moxonidina. A las 12 h de la PARA se administró la Escala de Gold modificada (EG) para valorar sintomatología de abstinencia (SAO). Resultados: Grupo A: clonidina: sólo un paciente presentó sintomatología (diarrea leve; EG = 1). Moxonidina: sintomatología en 2 pacientes (bostezos y sudación, respectivamente). En ambos pacientes la puntuación total en la EG fue de 1. Grupo B: clonidina: síntomas en 2 pacientes (diarrea y náuseas, respectivamente). En ambos casos la puntuación en la EG fue de 1. Moxonidina: síntomas en todos los pacientes (puntuación total en la EG entre 13 y 36 puntos, indicativos de mal control del SAO). Todos los pacientes experimentaron descenso de la temperatura corporal (0,4-0,9 ºC). Conclusiones: La moxonidina no es tan efectiva como la clonidina en control del SAO en las PARA. El uso de moxonidina obliga a aumentar las dosis de benzodiacepinas para conseguir un nivel similar de sedación que con clonidina. El descenso de temperatura obliga a monitorizar mejor este parámetro que en los tratamientos con clonidina. Nuestros resultados sugieren que el SAO podría trascender más allá del sistema noradrenérgico (AU)