Lesiones ampollares en una paciente con morfea panesclerótica discapacitante de la infancia / Bullous lesions in a patient with panesclerotic morphea of the childhood

La morfea ampollar es un tipo enfrecente de esclerodermia localizada que se caracteriza por presentar ampollas sobre placas escleróticas. La presencia de este tipo de lesiones obliga a descartar la variante extraenital de liquen esclerodemias localizadas, es posible hallar ambas afecciones. Se describe el caso de una paciente de 19 años con diagnóstico de morfea panesclerótica y liquen escleroso ampollar.

Bollous morphea is an infreqent type of morphea characterized for developing bullae on sclerodermiformic plaques. The presence of bullae forces to discard lichen sclerosus, a disease that usually develops in the genital zone, the extragenital variant could belong to the same spectrum that localized sclerodermiformic diseases. We present a 19 year old female patient with the diagnosis of panesclerotic morphea and bullous lichen sclerosus.

Does the association of tacrolimus and mycophenolate mofetil change the healing of the abdominal wall? study in rats submitted to ischemia and kidney reperfusion / A associação de tacrolimus e micofenolato mofetil altera a cicatrização da parede abdominal? estudo em ratos submetidos à isquemia e reperfusão renal

ABSTRACT Background: Tacrolimus and mycophenolate mofetil are immunosuppressive agents widely used on the postoperative period of the transplants. Aim: To evaluate the influence of the association of them on the abdominal wall healing in rats. Methods: Thirty-six Wistar rats were randomly assigned in three groups of 12. On the early postoperative period, four of the control group and three of the experimental groups died. The three groups were nominated as follow: control group (GC, n=8); group I (GI, n=11, standard operation, mycophenolate mofetil and tacrolimus); group II (GII, n=10, standard operation, mycophenolate mofetil and tacrolimus). The standard operation consisted of right total nephrectomy and 20 min ischemia of the left kidney followed by reperfusion. Both NaCl 0.9% and the immunosuppressive agents were administered starting on the first postoperative day and continuing daily until the day of death on the 14th day. On the day of their deaths, two strips of the anterior abdominal wall were collected and submitted to breaking strength measurement and histological examination. Results: There were no significant differences in wound infection rates (p=0,175), in the breaking strength measurement and in the histological examination among the three groups. Conclusion: The combination of the immunosuppressive agents used in the study associated with renal ischemia and reperfusion does not interfere in the abdominal wall healing of rats.

RESUMO Racional: O tacrolimus e o micofenolato mofetil são imunossupressores amplamente utilizados no pós-operatório dos transplantes de órgãos. Objetivo: Avaliar os efeitos deles sobre a cicatrização da parede abdominal em ratos. Métodos: Foram utilizados 36 ratos Wistar, distribuídos aleatoriamente em três grupos de 12. No pós-operatório imediato, quatro do grupo controle e três do grupo experimentação morreram. Os três grupos receberam as seguintes denominações: grupo controle (GC, n=8); grupo I (GI, n=11, operação-padrão, micofenolato mofetil e tacrolimus); grupo II (GII, n=10, operação-padrão, micofenolato mofetil e tacrolimus). A operação-padrão consistiu de nefrectomia total à direita, isquemia durante 20 min seguida de reperfusão do rim esquerdo. Solução de NaCl 0,9% e micofenolato mofetil + tracolimus foram administradas a partir do 1° dia do pós-operatório e mantidas até o dia do sacrifício dos animais, no 14° dia. Na data do sacrifício, foram retirados dois fragmentos da parede abdominal para análise da resistência à ruptura e exame histológico. Resultados: Não houve diferença estatisticamente significativa no índice de infecção de ferida operatória (p=0,175), nos valores de resistência de ruptura e nos achados histopatológicos entre os três grupos de animais. Conclusão: Os esquemas de imunossupressão empregados associados ao fenômeno da isquemia-reperfusão renal não induzem fraqueza significativa da cicatriz da parede abdominal em ratos no 14° dia de pós-operatório.

Desafíos terapéuticos en la enfermedad injerto contra huésped / Therapeutic challenges in graft versus host disease

La enfermedad injerto contra huésped es una entidad en la cual las células inmunológicas competentes de un tejido injertado reconocen y dañan antígenos presentes en el receptor del trasplante, que es incapaz de defenderse de ellas. Es una complicación frecuente del trasplante alogénico de médula ósea, y con menor frecuencia se produce luego de trasplantes de órganos sólidos o transfusiones de hemoderivados no irradiados. Se comunica el caso de una paciente de sexo femenino de 23 años, con leucemia linfoblástica aguda.y trasplante alogénico de médula ósea, que presentó una enfermedad injerto contra huésped con compromiso cutáneo y gastrointestinal dependiente de corticoides, con mejoría de los signos y síntomas cutáneos luego del tratamiento con infliximab y fotoféresis extracorpórea. (AU)

Graft versus host disease is an entity in which competent grafted immune cells recognize and damage tissue antigens present in the transplant recipient, who is unable to defend from them. It is one of the most serious complications in patients undergoing allogeneic bone marrow transplantation, although less frequently it may be associated with solid organ transplants or transfusions of not irradiated blood products. We report the case of a 23 year-old patient with acute lymphoblastic leukemia and allogeneic bone marrow transplantation, that presented graft versus host disease with skin and gastrointestinal involvement, dependent on corticosteroids, that showed improvement in signs and skin symptoms after treatment with infliximab and extracorporeal photopheresis. (AU)

Conversion to Mycophenolate Mofetil Monotherapy in Liver Recipients: Calcineurin Inhibitor Levels are Key

Abstract: The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow- up. Conversion was classified as successful (SC) if rejection did not occur during the follow-up. MMF conversion was successful with 28 patients (70%) and was associated with higher glomerular filtration rates at the end of study. It also correlated with increased time elapsed since transplantation, low baseline CNI levels (Tacrolimus ≤ 6.5 ng/mL or Cyclosporine ≤ 635 ng/mL) and lower frequency of tacrolimus use. The only clinical variable independently related to SC in multivariate analysis was low baseline CNI levels (p = 0.02, OR: 6.93, 95%, CI: 1.3-29.7). Mean baseline fluorescent intensity of FOXP3+ T cells was significantly higher among recipients with SC. In conclusion, this study suggests that baseline CNI levels can be used to identify recipients with higher probability of SC to MMF monotherapy. Clinicaltrials.gov identification: NCT01321112.

Cyclosporine Sparing Effect of Enteric-Coated Mycophenolate Sodium in De Novo Kidney Transplantation

PURPOSE: The increased tolerability of enteric-coated mycophenolate sodium (EC-MPS), compared to mycophenolate mofetil, among kidney transplant recipients has the potential to facilitate cyclosporine (CsA) minimization. Therefore, a prospective trial to determine the optimum EC-MPS dose in CsA-based immunosuppression regimens is necessary. MATERIALS AND METHODS: A comparative, parallel, randomized, open-label study was performed for 140 patients from four centers to compare the efficacy and tolerability of low dose CsA with standard dose EC-MPS (the investigational group) versus standard dose CsA with low dose EC-MPS (the control group) for six months in de novo kidney transplant recipients. Graft function, the incidence of efficacy failure [biopsy-confirmed acute rejection (BCAR), death, graft loss, loss to follow-up], and adverse events were compared. RESULTS: The mean estimated glomerular filtration rate (eGFR) of the investigational group at six months post-transplantation was non-inferior to that of the control group (confidence interval between 57.3 mL/min/1.73m² and 67.4 mL/min/1.73 m², p0.05) in the incidence of discontinuations and serious adverse events (SAE) between the groups. CONCLUSION: CsA minimization using a standard dose of EC-MPS kept the incidence of acute rejection and additional risks as low as conventional immunosuppression and provided therapeutic equivalence in terms of renal graft function and safety issues.

Mycophenolate mofetil as an immunomodulator in refractory noninfectious uveitis / Micofenolato mofetila como agente imunomodulador no tratamento das uveítes não infecciosas refratárias

ABSTRACT Purpose: To evaluate the efficacy and tolerance of mycophenolate mofetil (MMF) for the treatment of noninfectious uveitis using the methods advocated by the Standardization of Uveitis Nomenclature (SUN) Working Group and to compare this with other studies of immunosuppression in ocular inflammation. Methods: Retrospective case series. Patients with noninfectious uveitis, followed at a tertiary Uveitis Service in São Paulo, Brazil, from 2007 to 2014 and receiving oral MMF for a minimum of 6 months, were retrospectively reviewed. After reaching an optimal dose of MMF, patients were evaluated after 6 (T6), 12 (T12), and 24 months (T24). The optimal dose varied for each patient (medium 2.2 g/day, range 1.0-3.0 g/day). The main outcome measures were: 1) success on achieving complete control of inflammation in both eyes and/or oral prednisone dosage reduction to ≤10 mg per day, and 2) the length of time required to reduce oral prednisone to ≤10 mg/day, partial control of ocular inflammation, and side effects. Results: In a cohort of 16 patients with refractory noninfectious uveitis, 67% reached the ideal prednisone dose after 1 year of MMF treatment and 83% after 2 years of MMF treatment. Complete or partial inflammation control was achieved in 43.7% at T12. Two patients (14%) had disease remission after 4.7 years of MMF treatment. Adverse effects were gastrointestinal disturbances, infection, insomnia, and liver function abnormalities at a rate of 0.03 patient-year each. Conclusions: This small retrospective case series is consistent with the literature concerning the high efficacy and moderate tolerability of MMF in noninfectious uveitis. Observation of patients should be continued for at least 1 year to clearly determine MMF efficacy.

RESUMO Objetivo: Avaliar a eficácia e tolerância do micofenolato de mofetila (MMF) para o tratamento das uveítes não infecciosas refratárias, utilizando os métodos de análises definidos pelo "Standardization of Uveitis Nomenclature Working Group." Método: Estudo retrospectivo de série de casos. Foram incluídos pacientes com uveíte não infecciosa, em tratamento oral com MMF por um período mínimo de seis meses, acompanhados no Serviço de Uveítes, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil, no período de 2007 a 2014. Todos os pacientes faziam uso de pelo menos um imunossupressor e apresentavam doença ocular ativa. Os pacientes foram avaliados aos seis meses (T6), 12 meses (T12) e 24 meses (T24) após atingir a dose ótima do MMF. A média da dose ótima foi 2,2g/dia (intervalo 1,0-3,0g/dia). Os principais desfechos analisados foram: 1) Sucesso no controle total da inflamação em ambos os olhos e/ou redução da dose de prednisona oral para ≤10 mg/dia; 2) Intervalo até a redução da prednisona oral para ≤10 mg/dia, controle parcial de inflamação ocular e efeitos adversos. Resultados: Na presente coorte com 16 pacientes com uveíte não infecciosa refratária, observou-se 67% e 83% de probabilidade de alcançar a dose ideal de prednisona em T12 e T24, respectivamente. Controle total ou parcial da inflamação foi observado em 43,7% dos pacientes em T12. Dois pacientes (14%) tiveram remissão da doença após 4,7 anos do início de MMF. Os efeitos adversos foram distúrbios gastrintestinais, infecção, insônia e anormalidade da função hepática com 0,03 eventos paciente-ano (PPY) respectivamente. Conclusões: Esta pequena série retrospectiva de casos ratifica os achados na literatura sobre a alta eficácia e tolerância moderada de MMF em uveítes não infecciosas. Uma importante observação é que, para melhor avaliar a eficácia do MMF, deve se esperar o intervalo mínimo de um ano.

Targeted preemptive therapy according to perceived risk of CMV infection after kidney transplantation

ABSTRACT Background: The identification of the best strategy to manage cytomegalovirus infection is hampered by uncertainties regarding the risk/benefit ratios of universal prophylaxis versus preemptive therapy, the impact of indirect cytomegalovirus effects and the associated costs. This study investigated the efficacy and safety of targeted preemptive therapy according to perceived risk of cytomegalovirus infection after kidney transplantation. Methods: 144 adult kidney transplant recipients were enrolled in this 12-month study. None received cytomegalovirus pharmacological prophylaxis. Only high risk patients (positive donor/negative recipient (D+/R−), use of induction therapy with antithymocyte globulin, treatment of rejection) received preemptive therapy based on the result of pp65 antigenemia test. Low-risk patients with symptoms related to cytomegalovirus were screened for pp65 antigenemia and treatment initiated if confirmed cytomegalovirus disease. Blinded cytomegalovirus DNAemia was collected weekly during the first three months. Results: The incidence of cytomegalovirus infection was 34% and cytomegalovirus disease was 17%. The incidence was 25% in D+/R−, 69% in those receiving induction with rabbit antithymocite globulin (r-ATG), 46% in those treated for acute rejection, and 28% in low risk patients. By week 3 DNAemia was observed in 30% of patients who were not treated for cytomegalovirus infection/disease, and values ≥2.169 UI/mL showed 61% sensitivity and 85% specificity to detect cytomegalovirus disease (AUC = 0.849 ± 0.042, p < 0.001). Using multivariate analysis, only anti-thymocyte globulin induction was associated with cytomegalovirus infection/disease whereas only expanded donor criteria and renal function at 30 days were associated with renal function 12 months after transplantation. Conclusion: Targeted preemptive therapy in patients with perceived higher risk for cytomegalovirus infection/disease was effective in preventing severe clinical presentation, including tissue invasive and late cytomegalovirus infection. This strategy is associated with direct and indirect cost-savings.

Eficacia y seguridad de rituximab en combinación con azatioprina o Mofetil micofenolato en pacientes adultos con diagnóstico de pénfigo refractario y con contraindicación a uso de corticoides por eventos adversos serios / Efficacy and safety of rituximab for the treatment of patients younger than 18 years with autoimmune encephalitis refractory to first-line therapy (immunoglobulin, corticoid pulses and plasmapheresis)

INTRODUCCIÓN: Antecedentes: El Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) ha recibido la solicitud de evaluar el uso del medicamento Rituximab (RTX) administrado en asociación a azatioprina o mofetil micofenolato (MMF) en pacientes con pénfigo seborreico refractario y con contraindicaciones para el uso de corticoides por eventos adversos serios, indicación actualmente no contemplada en el petitorio de medicamentos. Aspectos Generales: El pénfigo es un grupo de enfermedades ampulosas autoinmunes raras caracterizado por formación de ampollas y erosiones extensas en la piel y las mucosas. El pénfigo aparece comúnmente en la edad adulta, su distribución es igual entre hombres y mujeres, y ocurre en todas las razas aunque se le ha encontrado asociado a algunos alelos del HLA clase II (Tron 2005), los cuales son moléculas heredadas relacionadas con la respuesta inmune. Fisiopatológicamente, las ampollas se producen debido a la presencia de auto-anticuerpos IgG contra la desmogleina 1 y 3 de los queratinocitos, las cuales son proteínas de adhesión localizadas en la parte superior e inferior de la epidermis respectivamente. Tecnología Sanitaria de Interés: Rituximab: RTX es un anticuerpo citolítico anti CD20. RTX se une al receptor del CD20 induciendo la disminución de células B in vitro. La molécula CD20 se expresa específicamente en la superficie de los linfocitos B durante su diferenciación desde células pre-B a células B maduras. El dominio Fab de RTX se une al antígeno CD20 de los linfocitos B, y el dominio Fc favorece funciones inmunes para mediar la lisis de las células B. Los posibles mecanismos de la lisis celular incluyen la citotoxicidad mediada por el sistema del complemento y mediada por anticuerpos (FDA). METODOLOGÍA: Estrategia de Búsqueda: Se realizó una búsqueda sistemática de la evidencia científica con respecto a la eficacia y seguridad de RTX en terapia combinada con azatioprina o MMFen pacientes con diagnóstico de pénfigo eritematoso refractario o con contraindicaciones para el uso de corticoides en las bases de datos MEDLINE, EMBASE y Translating research into practice (TRIPDATABASE), así como dentro de la información generada por grupos que realizan revisiones sistemáticas, evaluación de tecnologías sanitarias y guías de práctica clínica, tales como The Cochrane Library, The National Institute for Health and Care Excellence (NICE), The National Guideline for Clearinghouse (NGC) and The Canadian Agency for Drugs and Technologies in Health (CADTH). Los desenlaces clínicos a evaluar fueron mortalidad, remisión sostenida (definida como control de la enfermedad por más de 6 meses), calidad de vida, reacciones adversas, y disminución de la dosis de medicamentos coadyuvantes. Se hizo una búsqueda adicional en www.clinicaltrials.qov, para poder identificar ensayos clínicos en curso o que no hayan sido publicados. RESULTADOS: Sinopsis de la Evidencia: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de RTX en terapia combinada con azatioprina o MMF en pacientes con diagnóstico de pénfigo foliáceo (incluyendo el eritematoso) refractario o con contraindicaciones para el uso de corticoides. No se encontró ensayos clínicos aleatorizados que evaluaran a RTX como tratamiento de pénfigo foliáceo con o sin comparación con azatioprina o MMF por lo que se ha incluido resultados de estudios observacionales. CONCLUSIONES: Hasta el momento, no se ha identificado evidencia directa para responder si el uso de RTX en terapia combinada con azatioprina o mofetil MMFes mas efectiva y segura que la terapia con azatioprina o mofetil MMFen pacientes con diagnóstico de pénfigo eritematoso refractario y con contraindicaciones para el uso de corticoides por eventos adversos serios. No se ha encontrado en la presente evaluación de tecnología sanitaria evidencia consistente que establezca cual es el beneficio neto atribuible al uso de RTX por sobre otros inmunosupresores en pacientes con pénfigo eritematoso refractario y con contraindicación de uso de CE por eventos adversos severos, considerando que a la fecha se disponen de otros inmunosupresores de tercera línea recomendados en las guías consensuadas del manejo de pénfigo. expuesto El Instituto de Evaluación de Tecnologías en Salud e Investigación-IETSI no aprueba el uso de RTX como una alternativa de tratamiento para pacientes con diagnóstico de pénfigo eritematoso refractario y con contraindicación a uso de CE por efectos adversos severos.

Trasplante renal en pacientes con anticuerpos dirigidos contra donante

En trasplante renal, los anticuerpos donante-específicos por ensayos de fase sólida predicen el rechazo temprano mediado por anticuerpos, incluso con resultados negativos de citometría de flujo o citotoxicidad dependiente del complemento. Aquí se describen los protocolos de inmunosupresión y los resultados a diez meses de cuatro pacientes en los que se detectó anticuerpos donante-específicos anti-antígenos leucocitarios humanos (HLA) por Luminex®, pero no detectados por el método de citotoxicidad dependiente de complemento (CDC) ni por citometría de flujo. Los cuatro pacientes recibieron tratamiento de inducción con 5 dosis de timoglobulina de 1.25 mg/kg y 5 dosis de inmunoglobulina intravenosa (IVIG) de 400 mg/kg. Además, uno recibió 20 mg de basiliximab el mismo día del trasplante y el día 4 postrasplante; otro recibió 3 sesiones de plasmaféresis en los días -5, -3, y -1 y eculizumab en dosis de 1200 mg antes del trasplante, 900 mg el día 1, and 600 mg por semana durante un mes. En todos los casos, la inmunosupresión de mantenimiento consistió en tacrolimus, micofenolato y deltisona. Todos presentaron buenos resultados en el corto plazo. Nuestra experiencia sugiere que los pacientes con anticuerpos donante-específicos anti-HLA detectados solo por Luminex® deben recibir un seguimiento estricto y que en esta población se pueden obtener buenos resultados a partir del uso de terapia de inducción con timoglobulina e IVIG.

In renal transplantation, donor specific antibodies (DSAs) detected by sensitive solid-phase assay foresee early antibody-mediated rejections, even with negative complement-dependent cytotoxicity or flow cytometry results. We describe the immunosuppression protocols and outcomes at 10 months of four renal transplant patients in whom anti-HLA DSAs were detected by Luminex® but not by CDC and flow cytometry. The four patients underwent induction treatment with five doses of thymoglobulin at 1.25 mg/kg and 5 doses of intravenous immunoglobulin (IVIG) at 400 mg/kg. In addition, one patient received 20 mg basiliximab on the day of transplant and on post-operative day 4; another patient underwent three sessions of plasmapheresis on days -5, -3, and -1 and also received 1200 mg eculizumab prior to transplant, 900 mg on day 1, and 600 mg each week during one month. In all of them, the maintenance immunosuppressive regimen consisted of tacrolimus, mycophenolate acid and deltisone. All patients had good short-term outcomes. Our findings suggest that patients with anti-HLA DSAs detected only by Luminex® should be monitored closely and can be treated successfully with induction therapy based on thymoglobulin and IVIG.

A pilot study on area under curve of mycophenolic acid as a guide for its optimal use in renal transplant recipients.

Background & objectives: The immunosuppressants administered to renal transplant subjects are usually monitored therapeutically to prevent graft rejection and drug toxicity. Mycophenolic acid (MPA) is an immunosuppressant. The present prospective study was undertaken to establish the utility of plasma level monitoring of MPA and to correlate it with clinical outcomes in renal transplant receipients. Methods: MPA plasma level at 2, 4 and 9 h and the area under concentration-time curve (AUC) were estimated using high performance liquid chromatography in 24 renal transplant recipients receiving immunosuppressant MPA plus tacrolimus and steroid. Results: There was wide inter-individual variation in MPA plasma level and the AUC. The incidences of gastrointestinal adverse drug events (diarrhoea and acidity) were significantly more in the high MPA AUC patients. Though biopsy proven acute rejection was not found, of the six subjects with lower MPA AUC (<30 mg.h/l), three were clinically diagnosed to develop tacrolimus nephrotoxicity. The Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI) scores represented better health related quality of life in lower MPA AUC than in the higher MPA AUC (>60 mg.h/l). Interpretation & conclusions: The present findings suggest the MPA AUC of 30 - 60 mg.h/l in the maintenance stage of renal transplant patients to have optimum clinical benefit and relegated adverse events profile indicating the usefulness of AUC of MPA with limited sampling strategy in optimizing its use.

Estudio de biodisponibilidad relativa entre dos formulaciones orales de micofenolato mofetilo en voluntarios sanos / Relative bioavailability study of two oral formulations of mycophenolate mofetil in healthy volunteers

Background: The bioequivalence of different formulations of a same pharmaceutical product must be tested empirically. Aim: To evaluate the relative bioavailability for an oralformulation of mycophenolate mofetil (MMF) (Linfonex™) compared to the reference formulation (Cellcept™) to determine the bioequivalence between both formulations. Material and Methods: A randomized, crossover, double-blind trial in 22 healthy male volunteers, who received a single oral dose of 1000 mg of Linfonex and Cellcept with a washout period of 10 days. Plasma levels of the drug were determined by high performance liquid chr ornatography. Plasma concentrations were plotted and maximum concentration, area under the plasma concentration versus time between 0 and 12 hours after administration and área under plasma concentration curve versus time after administration between 0 and infinity, were calculated for both products. Results: The active compound, mycophenolic acid, was similarly absorbed in both formulations. No statistically significant differences were found in calculated pharmacokinetic parameters between both formulations. Conclusions: Linfonex™ 500 mg is bioequivalent to Cellcept™ 500 mg.

Improved Gastrointestinal Symptoms and Quality of Life after Conversion from Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium in Renal Transplant Patients Receiving Tacrolimus

It is reported that a conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) relieves gastrointestinal (GI) symptom burden and improves health-related quality of life (HRQoL). However, it is unclear whether renal transplant recipients using tacrolimus receive the same benefit from the conversion. In this prospective, multi-center, open-label trial, patients were categorized into two groups by their GI symptom screening. Equimolar EC-MPS (n=175) was prescribed for patients with GI burdens; those with no complaints remained on MMF (n=83). Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI) were evaluated at baseline and after one month. Patients and physicians completed Overall Treatment Effect (OTE) at one month. EC-MPS-converted patients had worse GSRS and GIQLI scores at baseline than MMF-continued patients (all P<0.001). Significant improvements in GSRS and GIQLI scores were observed for EC-MPS-converted patients at one month, but MMF-continued patients showed worsened GSRS scores (all P<0.05). OTE scale indicated that EC-MPS patients improved in overall GI symptoms and HRQoL more than MMF patients did (P<0.001). In tacrolimus-treated renal transplant recipients with GI burdens, a conversion from MMF to EC-MPS improves GI-related symptoms and HRQoL.

Synergistic effect of mycophenolate mofetil and angiotensin-converting enzyme inhibitor in patients with chronic allograft nephropathy

Experimental data and few clinical non-randomized studies have shown that inhibition of the renin-angiotensin system by angiotensin-converting enzyme (ACE) associated or not with the use of mycophenolate mofetil (MMF) could delay or even halt the progression of chronic allograft nephropathy (CAN). In this retrospective historical study, we investigated whether ACE inhibition (ACEI) associated or not with the use of MMF has the same effect in humans as in experimental studies and what factors are associated with a clinical response. A total of 160 transplant patients with biopsy-proven CAN were enrolled. Eighty-one of them were on ACE therapy (G1) and 80 on ACEI_free therapy (G2). Patients were further stratified for the use of MMF. G1 patients showed a marked decrease in proteinuria and stabilized serum creatinine with time. Five-year graft survival after CAN diagnosis was more frequent in G1 (86.9 vs 67.7 percent; P < 0.05). In patients on ACEI-free therapy, the use of MMF was associated with better graft survival. The use of ACEI therapy protected 79 percent of the patients against graft loss (OR = 0.079, 95 percentCI = 0.015-0.426; P = 0.003). ACEI and MMF or the use of MMF alone after CAN diagnosis conferred protection against graft loss. This finding is well correlated with experimental studies in which ACEI and MMF interrupt the progression of chronic allograft dysfunction and injury. The use of ACEI alone or in combination with MMF significantly reduced proteinuria and stabilized serum creatinine, consequently improving renal allograft survival.

Mycophenolate mofetil versus Rapamycin in Han: SPRD rats with Polycystic Kidney Disease

Objective: We aimed to explore the effect of Mycophenolate mofetil (MMF) on loss of renal function and cyst progression compared to rapamycin in Han: SPRD rats. We also sought to assess whether the effect of combination therapy of MMF plus rapamycin was better than that of monotherapy. Methods: Sixty heterozygous (Cy/+) and littermate control (+/+) male Han: SPRD rats were weaned at 4 weeks of age, then divided into four groups randomly to receive different treatments by intragastric administration for 2 months: vehicle-treated group as control, MMF-treated group (20mg/kg/day), rapamycin-treated group (2mg/kg/day), and MMF+Rapa- treated group (MMF 20mg/kg/day plus Rapamycin 2mg/kg/day). Resulls: After 2 months of treatment, rapamycin caused a 22 percent decrease in body weight in comparison to the control group, whereas MMF had no significant effect on weight gain. The steady increase of BUN in Cy/+ rats was reduced by 15 percent in MMF-treated Cy/+ rats. However, rapamycin and combination therapy reduced BUN by 42 percent and 43 percent, respectively. CCr was 0.93±0.11ml/min in vehicle-treated Cy/+ rats, 1.67±0.23 ml/min in MMF-treated Cy/+ rats (P<0.05), 1.72±0.44 ml/min and 1.83±0.21 ml/min in rapamycin- and MMF+Rapa-treated Cy/+ rats, respectively (.P<0.01). Cyst volume density was 57.1 percent in vehicle-treated Cy/+ rats, 45.2 percent in MMF-treated Cy/+ rats (P<0.05), 32.9 percent and 37.7 percent in rapamycin- and MMF+Rapa-treated Cy/+ rats, respectively (P<0.01). MMF markedly ameliorated interstitial inflammation and fibrosis. Rapamycin showed a similar effect on interstitial inflammation and fibrosis, but to a lesser degree. Conclusion : MMF is more tolerable than rapamycin and can retard deterioration of renal function in Han: SPRD rats, though its effect is weaker than that of rapamycin. Combination therapy does not exert more favorable effect than monotherapy.

Mycophenolate mofetil as adjuvant in pemphigus vulgaris.

Pemphigus vulgaris (PV) is a life threatening autoimmune blistering disease of skin and mucous membranes. Advent of systemic steroids has greatly reduced the mortality rate. However, steroids and adjuvant immunosuppressive therapy are nowadays frequent contributory agents of morbidity and mortality of PV. Mycophenolate mofetil (MMF) has been reported to be an effective adjuvant to systemic steroids. It helps in increasing the immunosuppressive effect and minimizing the toxicities by steroid sparing effect. However, its efficacy in refractory cases of PV is not well documented. The lowest possible dose with satisfactory therapeutic efficacy and least side effects is known. We used MMF 1 g/day and systemic steroids in 3 Indian patients with pemphigus vulgaris who were resistant to systemic steroid monotherapy or combination treatment with azathioprine. In our experience, MMF offers an effective adjuvant with minimal side-effects in the treatment of resistant PV.

Retiro precoz de esteroides en la inmunosupresión del trasplante renal pediátrico / Early steroid withdrawal in pediatric renal transplantation

Background: Cardiovascular risk, growth failure and the new immunosuppressive drugs, have encouraged steroid withdrawal or total avoidance with promising results in renal transplant (Tx) immunosuppression. Aim: To evaluate a new immunosuppressor protocol with early withdrawal of steroids in pediatric kidney transplant. Patients and methods: Prospective study in pediatric patients older than 1 year and low immunological risk. Group A (n =28): steroids in decreasing doses until day 7 post Tx, tacrolimus (FK) and micophenolate mofetil (MMF). Group B (n =28) control: steroids, cyclosporine and azathioprine or steroids, FK and MMF. In both groups the induction therapy included basiliximab. Anthropometric and biochemical variables (renal function, lipid profile, hematological, blood glucose and acid-base equilibrium), acute rejection and CMV infection, were evaluated. Mean values and variations for continuous variables were calculated at months 1, 6, 12 and 18. Results: Two children were withdrawn before month 2, one had an untreatable diarrhea and the second died due to Aspergillus septicemia. Mean values at months 1, 6, 12 and 18 for groups A and B: Creatinine clearence (ml/min): 85.4 vs 89; 79.9 vs 83; 89 vs 80; 79.8 vs 80.6 (p: ns); hematocrit ( percent): 28.8 vs 30.4; 31.7 vs 34.4; 34.4; 32.4 vs 34.8; 34.4 vs 35.5 (p: ns). Total cholesterol (mg/dl): 151 vs 206; 139 vs 174; 138 vs 186; 140 vs 180 (p <0.05). Mean delta height/age Z score at the first year: 0.5 vs 0.15; 0.7 vs 0.22; 0.97 vs 0.25 (p <0.05). Mean systolic blood pressure Z score: 0.9 vs 1.5; 0.5 vs 0.9; -0.3 vs 0.8; 0.1 vs 1.0 (p <0.05). The height/age Z score was significantly superior in patients without steroids. A normalization of growth patterns at month 18 was observed (< 0.05). Both groups presented a negative variation of creatinine clearance during the follow-up, but it was minor in the study group (p <0.05). Two acute rejections were found in each group, and no difference in CMV infections...

Impact of initial exposure to calcineurin inhibitors on kidney graft function of patients at high risk to develop delayed graft function

We conducted a retrospective analysis of the influence of full doses of calcineurin inhibitors [8-10 mg kg-1 day-1 cyclosporine (N = 80), or 0.2-0.3 mg kg-1 day-1 tacrolimus (N = 68)] administered from day 1 after transplantation on the transplant outcomes of a high-risk population. Induction therapy was used in 13 percent of the patients. Patients also received azathioprine (2 mg kg-1 day-1, N = 58) or mycophenolate mofetil (2 g/day, N = 90), and prednisone (0.5 mg kg-1 day-1, N = 148). Mean time on dialysis was 79 ± 41 months, 12 percent of the cases were re-transplants, and 21 percent had panel reactive antibodies >10 percent. In 43 percent of donors the cause of death was cerebrovascular disease and 27 percent showed creatinine above 1.5 mg/dL. The incidence of slow graft function (SGF) and delayed graft function (DGF) was 15 and 60 percent, respectively. Mean time to last dialysis and to nadir creatinine were 18 ± 15 and 34 ± 20 days, respectively. Mean creatinine at 1 year after transplantation was 1.48 ± 0.50 mg/dL (DGF 1.68 ± 0.65 vs SGF 1.67 ± 0.66 vs immediate graft function (IGF) 1.41 ± 0.40 mg/dL, P = 0.089). The incidence of biopsy-confirmed acute rejection was 22 percent (DGF 31 percent, SGF 10 percent, IGF 8 percent). One-year patient and graft survival was 92.6 and 78.4 percent, respectively. The incidence of cytomegalovirus disease, post-transplant diabetes mellitus and malignancies was 28, 8.1, and 0 percent, respectively. Compared to previous studies, the use of initial full doses of calcineurin inhibitors without antibody induction in patients with SGF or DGF had no negative impact on patient and graft survival.