Factores de riesgo ambientales no ocupacionales asociados al cáncer vesical / Environmental non-occupational risk factors associated with bladder cancer

Contexto: El carcinoma vesical (CV), por su elevada morbilidad y evolución recidivante, genera importantes costes asistenciales y económicos. Por ello revisaremos los factores de riesgo (FR) ambientales no ocupacionales implicados, con mayor o menor evidencia científica, en la etiopatogenia del CV, pues la implicación de los urológos es fundamental para su prevención. Adquisición de evidencia: Revisión bibliográfica de los últimos 25 años de los mencionados FR asociados al CV, obtenida de MedLine, Science Citation Index y Embase. Los perfiles de búsqueda han sido Risk Factors/Epidemiology/Tobacco-smoking/Diet-nutrition-water-liquids/Infectious/Radiation/Farmacological drugs y Bladder cancer. Síntesis de evidencia: El tabaquismo se asocia al 50% de los CV en ambos sexos. Los fumadores presentan riesgos 2-5 veces superiores, dependiendo de la intensidad y duración de la adicción. El agua potable contaminada con arsénico, subproductos de cloración y cromo, incrementa el riesgo de CV. Consumos altos de carne roja y grasa saturada posiblemente aumenten el riesgo, mientras la ingesta elevada de frutas y verduras lo disminuye. La administración de ciclofosfamida, ifosfamida y radioterapia incrementa el riesgo de CV. El uso frecuente y prolongado de tintes capilares y la infestación por Schistosoma haematobium se asocian a mayores riesgos. Conclusiones: La reducción o eliminación del tabaquismo disminuirá la prevalencia del CV. El consumo de agua sin contaminantes, con el incremento de alimentos vegetales favorece la prevención del CV. Los supervivientes de cánceres tratados con ciclofosfamida, ifosfamida y radioterapia deben ser monitorizados para el diagnóstico precoz del CV (AU)

Context: Bladder carcinoma (BC), due its high morbidity and relapsing course, generates significant economic and health care costs. Accordingly, review the environmental nonoccupational risk factors (RF), more or less evidence-based, in the etiology and pathogenesis of BC, because the involvement of urologists is essential for prevention. Acquisition of evidence: Review of the peer-reviewed literature (1987-2012) on nonoccupational environmental RF associated with BC retrieved from Medline, Embase and Science Citation Index. The search profiles have been «Risk factors/Epidemiology/Tobacco-smoking/Diet-nutrition-water-liquids/Radiation/Infectious/Farmacological drugs» and «Bladder cancer». Synthesis of evidence: Smoking was associated with 50% of BC in both sexes. Smokers have a 2-5 times higher risk than nonsmokers, directly proportional to the amount and duration of addiction. Drinking water contaminated with arsenic and chromium chlorination byproducts increases the risk of BC. High consumption of red meat and saturated fat may increase the risk, while high intake of fruits and vegetables decreases it. Patients treated with cyclophosphamide, ifosfamide and ionizing radiation have an increased risk of BC. Frequent and prolonged use of hair dyes and Schistosoma haematobium infestation increases the risk of BC. Conclusions: The reduction or the cessation of smoking decrease BC. The contaminant-free water consumption with the increase of vegetal foods favour BC prevention. Cancer survivors treated with cyclophosphamide, ifosfamide and radiation therapy should be monitored for early diagnosis of BC (AU)

Factores de riesgo constitucionales y ocupacionales asociados al cáncer vesical / Constitutional and occupational risk factors associated with bladder cancer

Objetivo: En los países occidentales el carcinoma vesical (CV) es el 4.° cáncer más frecuente en varones, siendo la prevención primaria un reto sanitario importante. Se revisan los factores de riesgo (FR) constitucionales y ocupacionales implicados, con mayor o menor evidencia científica, en la etiopatogenia del CV. Material y métodos: Revisión bibliográfica de los últimos 25 años de los FR constitucionales y ocupacionales asociados al CP, obtenida de MedLine, CancerLit, Science Citation Index y Embase. Los perfiles de búsqueda han sido Risk factors/Genetic factors/Genetic polymorphisms/Epidemiology/Occupational factors y Bladder cancer. Resultados: Los principales FR son: a) edad y sexo (se diagnostica en mayores de 65 años con una relación hombre/mujer de 4/1); b) étnico-raciales y geográficos (predominio en caucásicos y los países del Sur de Europa); c) genéticos (las mutaciones del gen N-acetil-transferasa 2 y el Glutation-S-transferasa-M1, incrementan significativamente el riesgo de CV); d) los FR ocupacionales representan el 5-10%; y f) las profesiones con mayores riesgos de CV son la producción de aluminio, manufactura de tintes, pinturas y colorantes, industria del caucho y la extracción y usos industriales de combustibles fósiles. Conclusiones: El CV es el resultado final de la combinación variable de los FR constitucionales y ambientales. Desconocemos la mayoría de FR implicados en los CV. Los FR constitucionales más decisivos son la edad y el sexo, los étnico-raciales-geográficos y los polimorfismos genéticos. Los principales FR ocupacionales corresponden a exposiciones a aminas aromáticas e hidrocarburos policíclicos aromáticos (AU)

Objective: Bladder carcinoma (BC) is the fourth most common type of cancer in males from Western countries, with primary prevention an important healthcare challenge. We review the associated constitutional and occupational risk factors (RF), with greater or lesser scientific evidence, in the aetiology of BC. Material and methods: Literature review of the last 25 years of the constitutional and occupational RF associated with BC, conducted on MedLine, CancerLit, Science Citation Index and Embase. The search profiles were Risk factors/Genetic factors/Genetic polymorphisms/Epidemiology/Occupational factors and Bladder cancer. Results: The main RF were a) age and gender (diagnosed at age 65 and over, with a 4:1 ratio of males to females); b) race, ethnicity and geographic location (predominantly in Caucasians and in Southern European countries); c) genetic (N-acetyltransferase-2 and glutathione s-transferase M1 gene mutations, which significantly increase the risk for BC); d) occupational, which represent 5%-10% of BC RF; and f) occupations with high BC risk, such as aluminium production, the manufacture of dyes, paints and colourings, the rubber industry and the extraction and industrial use of fossil fuels. Conclusions: BC is the end result of the variable combination of constitutional and environmental RF, the majority of which are unknown. The most significant constitutional RF are related to age, gender, race, ethnicity geographic location and genetic polymorphisms. The main occupational RF are those related to aromatic amines and polycyclic aromatic hydrocarbons (AU)

Constitutional and occupational risk factors associated with bladder cancer.

OBJECTIVE: Bladder carcinoma (BC) is the fourth most common type of cancer in males from Western countries, with primary prevention an important healthcare challenge. We review the associated constitutional and occupational risk factors (RF), with greater or lesser scientific evidence, in the aetiology of BC. MATERIAL AND METHODS: Literature review of the last 25 years of the constitutional and occupational RF associated with BC, conducted on MedLine, CancerLit, Science Citation Index and Embase. The search profiles were Risk factors/Genetic factors/Genetic polymorphisms/Epidemiology/Occupational factors and Bladder cancer. RESULTS: The main RF were a) age and gender (diagnosed at age 65 and over, with a 4:1 ratio of males to females); b) race, ethnicity and geographic location (predominantly in Caucasians and in Southern European countries); c) genetic (N-acetyltransferase-2 and glutathione s-transferase M1 gene mutations, which significantly increase the risk for BC); d) occupational, which represent 5%-10% of BC RF; and f) occupations with high BC risk, such as aluminium production, the manufacture of dyes, paints and colourings, the rubber industry and the extraction and industrial use of fossil fuels. CONCLUSIONS: BC is the end result of the variable combination of constitutional and environmental RF, the majority of which are unknown. The most significant constitutional RF are related to age, gender, race, ethnicity geographic location and genetic polymorphisms. The main occupational RF are those related to aromatic amines and polycyclic aromatic hydrocarbons.

Environmental non-occupational risk factors associated with bladder cancer.

CONTEXT: Bladder carcinoma (BC), due its high morbidity and relapsing course, generates significant economic and health care costs. Accordingly, review the environmental nonoccupational risk factors (RF), more or less evidence-based, in the etiology and pathogenesis of BC, because the involvement of urologists is essential for prevention. ACQUISITION OF EVIDENCE: Review of the peer-reviewed literature (1987-2012) on nonoccupational environmental RF associated with BC retrieved from Medline, Embase and Science Citation Index. The search profiles have been "Risk factors/Epidemiology/Tobacco-smoking/Diet-nutrition-water-liquids/Radiation/Infectious/Farmacological drugs" and "Bladder cancer". SYNTHESIS OF EVIDENCE: Smoking was associated with 50% of BC in both sexes. Smokers have a 2-5 times higher risk than nonsmokers, directly proportional to the amount and duration of addiction. Drinking water contaminated with arsenic and chromium chlorination byproducts increases the risk of BC. High consumption of red meat and saturated fat may increase the risk, while high intake of fruits and vegetables decreases it. Patients treated with cyclophosphamide, ifosfamide and ionizing radiation have an increased risk of BC. Frequent and prolonged use of hair dyes and Schistosoma haematobium infestation increases the risk of BC. CONCLUSIONS: The reduction or the cessation of smoking decrease BC. The contaminant-free water consumption with the increase of vegetal foods favour BC prevention. Cancer survivors treated with cyclophosphamide, ifosfamide and radiation therapy should be monitored for early diagnosis of BC.

Could other viruses cause pediatric posttransplant lymphoproliferative disorder?

INTRODUCTION: Posttransplant lymphoproliferative disorder (PTLD) constitutes a heterogeneous group of diseases. We summarize the experience of our hospital, one of Spain's largest series of renal (294), liver (47) and allogeneic stem cell transplants (67), where four cases of PTLD have developed related to complex viral infections. METHODS: Case 1 was a 24-month-old boy diagnosed with acute lymphoblastic leukemia who underwent allogeneic stem-cell transplantation (SCT). He was seropositive for Epstein-Barr virus (EBV) and developed an aggressive Bcell non-Hodgkin's lymphoma (B-NHL) related to EBV reactivation and human herpesvirus 6 (HHV-6) infection. Cases 2, 3, and 4 developed after kidney transplantation and were all EBV seronegative. Case 2 had associated cytomegalovirus (CMV) and EBV infection. Cases 3 and 4 only revealed EBV viral load. Cases 1, 3, and 4 progressed rapidly, with fatal outcome. Global incidence of PTLD in our series is 1.1%. CONCLUSION: PTLD is a rare but life-threatening condition. Although EBV plays a clear role in its pathogenesis, other associated viral infections could trigger this situation. Current therapies include rituximab, decreasing immunosuppressive drugs. and conventional chemotherapy.

Could other viruses cause pediatric posttransplant lymphoproliferative disorder?

INTRODUCTION: Posttransplant lymphoproliferative disorder (PTLD) constitutes a heterogeneous group of diseases. We summarize the experience of our hospital, one of Spain's largest series of renal (294), liver (47) and allogeneic stem cell transplants (67), where four cases of PTLD have developed related to complex viral infections. METHODS: Case 1 was a 24-month-old boy diagnosed with acute lymphoblastic leukemia who underwent allogeneic stem-cell transplantation (SCT). He was seropositive for Epstein-Barr virus (EBV) and developed an aggressive Bcell non-Hodgkin's lymphoma (B-NHL) related to EBV reactivation and human herpesvirus 6 (HHV-6) infection. Cases 2, 3, and 4 developed after kidney transplantation and were all EBV seronegative. Case 2 had associated cytomegalovirus (CMV) and EBV infection. Cases 3 and 4 only revealed EBV viral load. Cases 1, 3, and 4 progressed rapidly, with fatal outcome. Global incidence of PTLD in our series is 1.1%. CONCLUSION: PTLD is a rare but life-threatening condition. Although EBV plays a clear role in its pathogenesis, other associated viral infections could trigger this situation. Current therapies include rituximab, decreasing immunosuppressive drugs. and conventional chemotherapy (AU)

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Dolor abdominal funcional: “criterios para un cambio” / Functional abdominal pain: “criteria for a change”

Una parte importante del dolor abdominal recurrentela constituyen los trastornos funcionales recogidosen los criterios de Roma. El objetivo de esteartículo es comentar las modificaciones más destacablesrealizadas en la última actualización, es decir,del Roma II de 1999 al Roma III del 2006. Sontres las modificaciones globales más destacables: a)se excluye a la aerofagia; b) se acorta el tiempo deduración de los síntomas necesario para el diagnóstico,pasando de tres a dos meses y c) exclusión delgrado de madurez en el desarrollo cognitivo del niñocomo criterio diagnóstico, incluyéndose niños a partirde los 4 años. Las modificaciones específicas paracada grupo más destacables son: a) dispepsiafuncional: se elimina la necesidad de realizar unaendoscopia digestiva alta para el diagnóstico; b) migrañaabdominal: se reduce la frecuencia y duraciónde los síntomas que deben afectar la actividad habitual.Los antecedentes familiares de migraña soncriterio de apoyo, no de diagnóstico; c) dolor abdominalfuncional: reducción de la frecuencia de la sintomatologíay la posibilidad de relacionarse coneventos psicosociales, pudiendo o no afectar a laactividad habitual del niño y c) no existen modificacionespara el síndrome de intestino irritable

Functional disorders, gathered in Rome criteria,constitute an important part of recurrent abdominalpain. The aim of this article is to comment the mostremarkable modifications made in the last update,that is, from the 1996 Rome II criteria to 2006 RomeIII criteria. Three are the most remarkable global modifications:a) aerophagia is excluded; b) durationterm of symptoms is reduced from three to twomonths and c) children cognitive mature degree isexcluded, including children older than 4 years. Themore remarkable modifications made in each specificgroup are: a) functional dyspepsia: the necessityof making an upper digestive endoscopy for thediagnosis is eliminated; b) abdominal migraine: frequencyand duration of symptoms that affect thenormal activity are reduced. Familiar antecedents ofmigraine are support criterion, they are not diagnosiscriterion; c) functional abdominal pain: reduction ofthe symptoms frequency, and the possibility to relatewith psycho – social events, that may affect the childrenhabitual activity, or may not; and d) there areno modifications about the irritable bowel syndrome

Orientación al diagnóstico y tratamiento del dolor abdominal crónico y dolor abdominal recurrente en el niño y adolescente / Diagnosis and treatment orientation for the chronic abdominal pain and recurrent abdominal pain in children and adolescents

La prevalencia del dolor abdominal de larga duraciónen niños es desconocida. Supone el 2-4% delas consultas pediátricas. Un dolor cuya duraciónsupere las 2-6 semanas se denomina dolor abdominalcrónico y si persiste más de 3 meses se denominadolor abdominal recurrente. Puede ser orgánico,somatomorfo o funcional En los menores de 4 añosel dolor abdominal recurrente se establece como un“diagnóstico”, no pudiéndose establecer el diagnósticode funcional. En los mayores de 4 años el dolorabdominal recurrente es un “síntoma” y se estableceel diagnóstico de funcional según los criterios deRoma III, basados en un conjunto de síntomas.Un interrogatorio y un examen físico completosson los componentes de mayor importancia en lavaloración de cualquier enfermo con dolor abdominalcrónico o recurrente. La causa orgánica se debeconsiderar siempre en primer lugar, principalmenteen menores de 4 años. La presencia de síntomas osignos de alarma constituye una indicación parapracticar pruebas diagnósticas. Una vez descartadaenfermedad orgánica o trastorno por somatización,podemos establecer el diagnóstico de dolor abdominalfuncional, en base a los criterios de Roma III queestablece las siguientes categorías: dispepsia funcional,síndrome de intestino irritable, migraña abdominaly dolor abdominal funcional.El niño con dolor abdominal crónico o recurrentese debe tratar en el contexto de un modelo asistencialbiopsicosocial

Prevalence of long term abdominal pain is unknown.It supposes about 2-4% of the pediatric consultations.Pain that lasts more than 2-6 weeks is calledchronic abdominal pain, and if it lasts more than3 months, it is called recurrent abdominal pain. Itcan be an organic disorder, a somatization disorderor a functional disorder. In children younger than 4years recurrent abdominal pain sets up as a “diagnosis”,as it can’t be established as a functional disorder.In older children, recurrent abdominal pain isa “symptom”, and the diagnosis of functional disorderis established according to Rome III criteria, thatare based upon a set of symptoms.Complete examination and physical exploration arethe main components in the valuation of any patientwith chronic or recurrent abdominal pain. Organiccause should be always considered in first place, moreoverin children younger than 4 years. Presence ofalarm symptoms or signs constitutes and indication toperform diagnostic tests. Once discarded organic diseaseor somatization disorder, we can establish thefunctional abdominal pain diagnosis, based upon theRome III criteria, that sets up the following categories:functional dyspepsia, irritable bowel syndrome, abdominalmigraine and abdominal functional pain.Children with chronic or recurrent abdominal painshould be treated in the context of a biopsicosocial assistant model (AU)

Obstructive uropathy in a HIV+ infant under indinavir treatment.

The case is presented of a 10-year-old HIV+ male with renoureteral pain, who developed an obstructive uropathy with renal function impairment and required endoscopic placement of a ureteral stent. Certain aspects of the epidemiology, clinical presentation, diagnosis, treatment and prevention are discussed.

Mycophenolate mofetil in steroid/cyclosporine-dependent/resistant nephrotic syndrome.

Attempts to minimize the effects of prolonged steroid use in steroid-dependent nephrotic syndrome (SDNS) and the need to overcome steroid resistance (SRNS) justifies immunosuppressant therapy. We report our experience in a cohort of patients with SD/SRNS during the administration of mycophenolate mofetil (MMF) in a prospective protocol initiated in January 2001. Twenty-six children with idiopathic nephrotic syndrome were included (21 steroid dependent and 5 steroid resistant), whose response did not change after sequential treatment with cyclophosphamide (CPM) and cyclosporine (CsA). Histopathologic patterns were: 11 minimal change disease (MCD), 1 diffuse mesangial proliferation (DMP), 13 focal segmental glomerulosclerosis (FSGS) and membranous 1 glomerulonephritis (MGN). The median age of onset of NS was 2.8 years (range 1.2-12.5), and treatment with MMF was performed at a median age of 11.4 years (range 5-17) with an initial dose of 600 mg/m(2)/12 h, adjusted to maintain levels of mycophenolic acid (MPA) at 2.5-5 mcg/ml. The planned duration of study to assess treatment efficacy was 6 months. The mean MMF dose required was 624 (SD=136) mg/m(2)/12 h (range 415-970), which maintained mean C(0)-MPA levels of 2.9 (SD=1.17) mcg/ml (range 1.2-5.9 mcg/ml). In the five patients with SRNS, only one achieved complete remission. In the patients with SDNS, steroid sparing was achieved in 15 and 9 remained in remission on MMF monotherapy. Withdrawal of MMF resulted in immediate relapse in 47%. In our study, MMF was a useful immunosuppressant due to its fewer undesirable effects and similar efficacy to other drugs used. It appears effective for the maintenance of remission in SDNS patients, with a response similar to that of CsA.

[Left renal vein hypertension syndrome]. / Síndrome de hipertensión vena renal izquierda.

INTRODUCTION: [corrected] Left renal vein compression, causing retrograde hypertension, determines a syndrome characterized by the presence of hematuria, gonadal vein dilatation and varicocele. Being a rare cause of hematuria its aetiology is diverse but of precise characteristics. Diagnosis is not easy and treatment requires to rule out its precise aetiology and consider the intensity of the compression phenomenon because of interventionist attitudes have important implications and are not risk free. MATERIAL AND METHODS: We report nine children, aged 8-15 years, presenting with hematuria of urologic characteristics. Diagnosis of left renal vein hypertension or nutcracker phenomenon was established through ultrasound (regular and doppler-ultrasound) and helical-TC performed in all, and left renal venography performed in six of them. RESULTS: Retroaortic renal vein was present in two cases, a varicose accessorial renal vein due to anomalous drainage in one and compression at the aortomesenteric space in six. Because of the symptoms severity therapeutic attitude was interventionist in two cases, performing an auto-transplantation in one, and endovascular stent placement al the level of the left renal vein compression in other. CONCLUSIONS: Diagnosis of this syndrome is not always easy because less invasive explorations usually show parameters that are difficult to distinguish from normality. Severity of clinical manifestations and therapeutic attitude are related with the presence of renal vein hyperpressure and collateral varicose circulation indicating the lack of compensation of a difficult drainage.

Síndrome de hipertensión vena renal izquierda / Left renal vein hypertension syndrome

Introducción: La compresión de la vena renal izquierda (VRI), a partir de la hiperpresiónretrógrada que provoca, define un síndrome caracterizado por hematuria,dilatación de vena gonadal y varicocele. De etiología variada pero de característicasconcretas, es una causa infrecuente de hematuria, de diagnóstico difícil y cuyo tratamientorequiere tanto una concreción etiológica como la valoración de la intensidaddel fenómeno de compresión. Todo ello, por las imbricaciones que pueden suponeren actitudes intervencionistas no siempre exentas de riesgos.Material y métodos: Se aportan nueve niños, con hematuria de características urológicasy de edad al inicio de la sintomatología de 8-15 años. En todos se realizó ecografíamodo B y doppler color en siete, con TAC helicoidal en todos y en seis de ellosvenografia renal selectiva, estableciendo el diagnóstico de síndrome de hipertensiónde vena renal izquierda (HVRI) o fenómeno de «cascanueces».Resultados: El diagnóstico fue de vena renal retroaórtica en dos casos, vena renalaccesoria varicosa por drenaje anómalo en uno y de compresión a nivel del espacioaorto-mesentérico en los seis restantes. La actitud terapéutica, intervencionista en doscasos ante su importante repercusión clínica, consistió en un autotrasplante renal y lacolocación de un stent a nivel de la zona de compresión en la VRI.Conclusiones: El diagnóstico del síndrome no siempre es fácil ya que las exploracionesmenos invasivas reflejan con frecuencia patrones en los que es difícil precisar ellímite de normalidad. La intensidad de las manifestaciones clínicas y con ello la actitudterapéutica está en relación a la existencia de circulación colateral varicosa y a lahiperpresión venosa renal, como indicadores de una falta de compensación de la dificultadde drenaje

Introduction: Left renal vein compression, causing retrograde hypertension, determinesa syndrome characterized by the presence of hematuria, gonadal vein dilatation and varicocele. Being a rare cause of hematuria its aetiology is diverse but of precisecharacteristics. Diagnosis is not easy and treatment requires to rule out its preciseaetiology and consider the intensity of the compression phenomenon because ofinterventionist attitudes have important implications and are not risk free.Material y methods: We report nine children, aged 8-15 years, presenting withhematuria of urologic characteristics. Diagnosis of left renal vein hypertension or nutcrackerphenomenon was established through ultrasound (regular and doppler-ultrasound)and helical-TC performed in all, and left renal venography performed in six ofthem.Results: Retroaortic renal vein was present in two cases, a varicose accessorialrenal vein due to anomalous drainage in one and compression at the aortomesentericspace in six. Because of the symptoms severity therapeutic attitude was interventionistin two cases, performing an auto-transplantation in one, and endovascular stent placemental the level of the left renal vein compression in other.Conclusions: Diagnosis of this syndrome is not always easy because less invasiveexplorations usually show parameters that are difficult to distinguish from normality.Severity of clinical manifestations and therapeutic attitude are related with the presenceof renal vein hyperpressure and collateral varicose circulation indicating the lack ofcompensation of a difficult drainage

[Cytomegalovirus nephrotic syndrome]. / Síndrome nefrótico infantil por citomegalovirus.

The case of a 5 months old infant with a nephrotic syndrome after neonatal cytomegalovirus infection is reported. Genomic amplification nested-PCR for CMV was positive in renal biopsy. Treatment with gancyclovir was effective to maintain nephrotic syndrome remission. We stresses the importance to discharge an infections cause of the nephrotic syndrome of newborns and infants due to the possibility on curative treatment.

Síndrome nefrótico infantil por citomegalovirus / Cytomegalovirus nephrotic syndrome

Se presenta el caso de un varón que a los 5 meses de vida desarrolla un Síndrome Nefrótico clínico-bioquímico, con serología positiva a CMV IgG e IgM. En la biopsia renal, incremento de matriz mesangial, ligera hipercelularidad y estudio histoquímico con anticuerpo policlonal anti-CMV negativo. El estudio de amplificación genómica nested-PCR múltiple, positivo para CMV. El tratamiento corticoideo estándar fue ineficaz, lográndose la remisión permanente del Síndrome Nefrótico tras la terapéutica antivírica con ganciclovir.Consideramos necesario descartar causa infecciosa ante todo Síndrome Nefrótico en el primer año de vida, dada la posibilidad de un tratamiento etiológico curativo (AU)

[Anti-CD25 monoclonal antibody against polyclonal antibodies in pediatric renal transplantation]. / Anticuerpo monoclonal anti-CD25 frente a anticuerpos policlonales en el trasplante renal pediátrico.

UNLABELLED: Although usually reversible, acute rejection of kidney graft is a negative factor in long-term graft survival. Commonly used in pediatric renal transplantation, immunosuppresive induction therapy is established to prevent it. New immunosuppressive agents have been developed in recent years and among them anti-CD25 monoclonal antibody appears to be specially interesting. AIM: To evaluate efficacy and safety of anti-CD325 monoclonal antibody (basiliximab) versus polyclonal antibodies as induction therapy in renal transplantation. MATERIAL AND METHODS: Thirty consecutive kidney transplants performed in children 4-16 years age in Hospital Infantil La Fe through 1997-2000. The first 15 patients received polyclonal antibodies as induction therapy, and 15 consecutive ones received monoclonal anti-CD25 antibodies. Receptor, donor and graft characteristics were similar in both groups. Also, maintenance immunosuppression was the same. RESULTS: The follow-up was over one year in all patients. Four patients in the polyclonal antibody group suffered one acute rejection episode and four other patients had some drug reaction. In the anti-CD25 treatment group there was one episode of acute graft rejection and no collateral effects were observed. Glomerular filtration rate, proteinuria, hypertension, infection episodes, graft and patient survival were similar in both groups. CONCLUSIONS: Induction therapy for pediatric renal transplantation with anti-CD25 antibody has been effective and safe. Compared with polyclonal antibodies as standard treatment, basiliximab reduced acute rejection episodes and had no collateral side effects. Graft and patient one year survival were identical in the two groups.

Anticuerpo monoclonal anti-CD25 frente a anticuerpos policlonales en el trasplante renal pediátrico / Efficacy of basiliximab versus policlonal antibodies as induction therapy in pediatric kidney transplantation

Introducción: Los episodios de rechazo agudo del injerto renal, aunque generalmente reversibles, constituyen un factor pronóstico negativo en la supervivencia del injerto a largo plazo. Su prevención es el objetivo a conseguir con la terapia inmunosupresora de inducción, generalizada en el trasplante renal pediátrico. Recientemente se han incorporado a ella nuevos agentes inmunosupresores, entre los que destaca el anticuerpo monoclonal anti-CD25 (basiliximab).Objetivo: Evaluar la eficacia y seguridad del anticuerpo monoclonal anti-CD25 (basiliximab) frente a los anticuerpos policlonales en la terapia de inducción del trasplante renal pediátrico.Material y métodos: Se analizan 30 trasplantes consecutivos, en niños de 4-19 años, realizados en el Hospital Infantil La Fe durante el período de 1997-2000.Las características del receptor, donante y trasplante en ambos grupos así como la inmunosupresión de mantenimiento fue similar, sólo se diferenciaban en la utilización de anticuerpos policlonales o monoclonales (anti-CD25) en la inmunosupresión de inducción, los 15 primeros recibieron anticuerpos policlonales y a los 15 siguientes anticuerpo monoclonal anti-CD25. Se realizó un seguimiento durante 12 meses.Resultados: En el grupo de los anticuerpos policlonales, 4 pacientes presentaron rechazo agudo, y se objetivaron 4 reacciones adversas al fármaco frente a un rechazo y ninguna reacción adversa en el grupo de los anticuerpos monoclonales anti-CD25, ambas diferencias fueron estadísticamente significativas (p < 0,01).El funcionalismo renal (filtrado glomerular, proteinuria, hipertensión), número de infecciones y supervivencia del paciente y del injerto no presentaron diferencias estadísticamente significativas entre ambos grupos.Conclusiones: El uso de anticuerpos monoclonales anti-CD25 (basiliximab) en la terapia de inducción del trasplante renal pediátrico ha resultado seguro, sin presentar reacciones adversas al fármaco ni incremento del número de infecciones, y eficaz con menor número de rechazos agudos y buen funcionalismo renal durante el primer año postrasplante. (AU)

Plasma PAI-1 levels in obese children--effect of weight loss and influence of PAI-1 promoter 4G/5G genotype.

An association between an increase in plasminogen activator inhibitor type 1 (PAI-1) and obesity, and also between elevated levels of PAI-1 and the presence of PAI-1 promoter 4G allele has been described in adults and can contribute to increased risk of cardiovascular disease. It has also been suggested that in adults a decrease in adiposity has beneficial effects on the haemostatic system. However, less information is available regarding adiposity and fibrinolysis in children. The aim of the present study is to evaluate the effect of weight loss and the influence of the PAI-1 promoter 4G/5G genotype on the fibrinolytic system and lipid parameters in obese children. The clinical groups included 102 obese children and 105 controls of similar age and sex distribution. A significant decrease in fibrinolytic activity due to a significant increase in PAI-1 antigen and activity levels was observed in the obese children in comparison with the control group. In obese children, no significant differences in PAI-1 levels between the PAI-1 4G/5G genotypes were obtained. A significant correlation was observed between PAI-1 antigenic and functional levels and body mass index (BMI), as well as between PAI-1 levels and both triglyceride and insulin levels. No correlation between PAI-1 levels and either cholesterol or glucose levels was observed. After a three-month period of treatment to reduce weight, an increase in fibrinolytic activity due to a decrease in PAI- levels was observed in the obese children who had reduced their BMI in comparison with the group of obese children who did not show a decrease in their BMI. No significant differences between the two groups with respect to the variations in tissue type plasminogen activator and fibrinogen levels were obtained after three months of intervention to reduce weight. A significant correlation was observed between variations in BMI and variations in PAI-1 levels, and a significant inverse correlation was also observed between previous PAI-1 levels and variation in PAI-1 levels. Therefore, the largest decrease in PAI-1 levels was observed in the obese children with the highest previous PAI-1 levels. In conclusion, a decrease in BMI in obese children shows a favourable effect on the fibrinolytic system due to a decrease in PAI-1 levels. However, no influence of 4G/5G genotype on PAI-1 levels was observed.