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1.
Yonsei Med J ; 62(2): 164-171, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33527796

RESUMO

PURPOSE: Calcineurin inhibitor (CNI) use has improved lung transplantation outcomes. However, significant perioperative complications in patients receiving CNI can deteriorate the early course of lung transplantation. To date, there is no consensus regarding the optimal agent for the induction regimen after lung transplantation. We aimed to determine the efficacy of basiliximab induction with delayed CNI initiation in the prevention of acute complications without compromising immunosuppression in high-risk patients. MATERIALS AND METHODS: Between January 2013 and December 2019, 236 patients at a single lung transplant center were retrospectively reviewed. Forty-one patients (17.4%) received basiliximab induction, and 195 patients (82.6%) received a routine triple-drug regimen without induction. The primary endpoint was postoperative acute kidney injury with several other postoperative outcomes as secondary end-points. RESULTS: Preoperatively, the induction group had a higher proportion of patients who were admitted before transplantation (95.1% vs. 47.7%, p<0.001) and received intensive unit care (90.2% vs. 33.8%, p<0.001) and extracorporeal membrane oxygenation (ECMO) (87.8% vs. 20.0%, p<0.001) compared to the non-induction group. No significant differences were observed in the incidence of acute rejection between groups (p=0.657), although lower incidence of postoperative complications, including acute kidney injuries or culture-proven infections, were observed in the induction group. However, the differences were not statistically significant. A subgroup analysis of high-risk and preoperative ECMO support groups showed similar results. CONCLUSION: Basiliximab induction with delayed CNI initiation for high-risk patients might decrease the incidence of perioperative complications, including acute renal failure, without increasing the risk of acute rejection.


Assuntos
Basiliximab/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Transplante de Pulmão , Creatinina/sangue , Oxigenação por Membrana Extracorpórea , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
2.
Medicine (Baltimore) ; 100(4): e24533, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530282

RESUMO

BACKGROUND: Evidence suggesting a role for including calcineurin inhibitors(CNIs) in early therapy remains limited for low quality and mainly based on small observation cohort study. We will conduct a systematic reviews to explore the effect and adverse effect of calcineurin inhibitors compared with other interventions in the treatment of primary focal segmental glomerulosclerosis (FSGS). METHODS: A comprehensive literature search of MEDLINE (through PubMed), EMBASE, The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL) will be conducted. Two investigators will independently select studies, extract data and assess the quality of the included study. Extracted information will include study characteristics, the contents of included randomized controlled trials, outcomes, the quality of randomized controlled trials and etc. A risk of bias tool will be used to assess the methodological quality. Any disagreement will be resolved by the third investigator. There is no requirement of ethical approval and informed consent. RESULTS: This study will provide high-quality evidence for treatment of FSGS in terms of effectiveness and safety. CONCLUSION: This systematic review aims to provide evidence for treatment of FSGS in different CNIs. REGISTRATION: The systematic review and meta-analysis is registered in the OSF REGISTERS (10.17605/OSF.IO/3B7DE) international prospective register of systematic review.


Assuntos
Inibidores de Calcineurina/uso terapêutico , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto
5.
Niger J Clin Pract ; 23(10): 1387-1394, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33047695

RESUMO

Background: Chronic kidney disease (CKD) is a common late complication in liver-transplanted patients who have received long-term therapy with calcineurin inhibitors (CNIs). Aims: To analyze kidney disease progression after liver transplantation. Methods: We analysed the clinical data of adult single-organ liver transplant recipients performed at our centre between October 2003 and September 2009. The patients with the estimated glomerular filtration rate (eGFR) greater than 60 ml/min/1.73 m2 before surgery were included in the study. Results: 69 patients with complete follow-up data were analysed. We found that eGFR at 1 or 2 years after liver transplantation correlated well with eGFR at 5 years. In addition, our results showed that patients whose eGFR declined below 60 at 2 years after liver transplantation would develop an irreversible renal injury in the following years. At 2 years, 12 patients had an eGFR less than 60, which were maintained in 11 patients at 5 years (Sensitivity = 11/12, 91.67%; Specificity = 57/58, 98.28%, Youden's index = 89.95%). The annual rate of eGFR reduction of the tacrolimus group was greater than that of the tacrolimus sparing group based on the value-time variation curve in our study. Moreover, the tacrolimus concentration influenced the CKD progression at 1 and 2 years with an under the ROC curve of 0.73 and 0.78 when Youden's index was at its maximum and the tacrolimus concentrations were 8.55 and 5.96 ng/ml, respectively. Conclusion: We confirmed that eGFR at 2 years after liver transplantation is useful for observing a meaningful change in eGFR and renal damage. Obtaining the appropriate serum concentration of an early decrease of the dose of CNIs and transforming non-nephrotoxic immunosuppressants would help improve renal function to prevent CKD progression and end-stage renal disease (ESRD).


Assuntos
Inibidores de Calcineurina/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Transplante de Fígado/efeitos adversos , Insuficiência Renal Crônica/complicações , Tacrolimo/uso terapêutico , Proteínas Adaptadoras de Transdução de Sinal , Adolescente , Adulto , Inibidores de Calcineurina/uso terapêutico , Progressão da Doença , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Fatores de Risco
6.
Gastroenterol. hepatol. (Ed. impr.) ; 43(8): 457-463, oct. 2020. graf
Artigo em Espanhol | IBECS | ID: ibc-196902

RESUMO

La infección por el virus SARS-CoV-2 ha producido una pandemia con graves consecuencias sobre nuestro sistema sanitario. Aunque el colectivo de pacientes trasplantados hepáticos representa solo una minoría de la población, los hepatólogos que seguimos a estos pacientes hemos intentado coordinar esfuerzos para protocolizar el manejo de la inmunosupresión durante la infección por SARS-CoV-2. Aunque no hay estudios sólidos que avalen recomendaciones generales, las experiencias con otras infecciones víricas (hepatitis C, citomegalovirus) sugieren que el manejo de la inmunosupresión sin micofenolato mofetilo ni inhibidores m-Tor (fármacos que además se asocian a leucopenia y linfopenia) puede resultar beneficiosa. Es importante además prestar atención a las posibles interacciones farmacológicas, especialmente en el caso de tacrolimus, con algunos de los tratamientos con efecto antiviral que se administran en el contexto de la covid-19 (lopinavir/ritonavir, azitromicina). Finalmente, deberá tenerse en cuenta el efecto inmunosupresor de fármacos inmunomoduladores (tocilizumab y similares) que se administran en pacientes con enfermedad pulmonar severa. En el artículo se revisan los mecanismos de actuación de los diferentes fármacos inmunosupresores, su potencial efecto sobre la infección por SARS-CoV-2 y se sugieren unas pautas en el manejo de la inmunosupresión


SARS-CoV-2 infection has produced a pandemic with serious consequences for our health care system. Although liver transplant patients represent only a minority of the population, the hepatologists who follow these patients have tried to coordinate efforts to produce a protocol the management of immunosuppression during SARS-CoV-2 infection. Although there are no solid studies to support general recommendations, experiences with other viral infections (hepatitis C, cytomegalovirus) suggest that management of immunosuppression without mycophenolate mofetil or m-Tor inhibitors (drugs that are also associated with leukopenia and lymphopenia) may be beneficial. It is also important to pay attention to possible drug interactions, especially in the case of tacrolimus, with some of the treatments with antiviral effect given in the context of COVID 19 (lopinavir/ritonavir, azithromycin). Finally, the immunosuppressive effect of immunomodulating drugs (tocilizumab and similar) administered to patients with severe lung disease should be taken into account. The mechanisms of action of the different immunosuppressive drugs are reviewed in this article, as well as their potential effect on SARS-CoV-2 infection, and suggests guidelines for the management of immunosuppression


Assuntos
Humanos , Imunossupressão/métodos , Transplante de Fígado/métodos , Infecções por Coronavirus/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Leucopenia/complicações , Linfopenia/complicações , Tacrolimo/uso terapêutico , Fatores Imunológicos/uso terapêutico , Glucocorticoides/antagonistas & inibidores , Inibidores de Calcineurina/uso terapêutico , Serina-Treonina Quinases TOR/uso terapêutico
7.
Medicine (Baltimore) ; 99(37): e22159, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925777

RESUMO

BACKGROUND: Long-term use of corticosteroid ointment for external using or skin management products and cosmetics containing corticosteroid will produce a hormone-dependent effect on facial skin and destroy the barrier function of the skin. It is easy to cause repeated attacks of facial skin inflammation after drug withdrawal because corticosteroid hormones can cause the expression of inflammatory factors in the body, which has a serious impact on patients. The general treatment method is to stop using hormone drugs for psychotherapy and inform patients of the basic knowledge of hormone-dependent dermatitis and daily facial care, but the effect is not good. At present, non-steroidal ointment tacrolimus (a calcineurin inhibitor) is widely used in the treatment of hormone-dependent dermatitis. Tacrolimus ointment is effective for corticosteroid-dependent dermatitis, but adverse events can also occur. METHODS: We plan to searched all randomized controlled trials (RCTs) fortacrolimus ointment therapy of hormone-dependent dermatitis in: MEDLINE, PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Springer and Web of Science, China Biomedical Literature Database (CBM), China Science Journal Database (VIP database) and Wanfang Database, China National Knowledge Infrastructure (CNKI), without the limitation of publication status and language until September 1, 2020. The systematic review will also search will also search for identify publications, meeting minutes, and grey literature (including unpublished meeting articles). DISCUSSION: The systematic review mainly to access the safety and efficacy of tacrolimus ointment for hormone-dependent dermatitis (facial corticosteroid addiction dermatitis and facial steroid dermatitis). The results of our research will facilitate evidence-based management of patients with facial corticosteroid-dependent dermatitis and provide clinical advice on their treatment options. REGISTRATION: PROSPERO CRD42020171813.


Assuntos
Corticosteroides/efeitos adversos , Inibidores de Calcineurina/uso terapêutico , Erupção por Droga/tratamento farmacológico , Erupção por Droga/etiologia , Tacrolimo/uso terapêutico , Administração Cutânea , Corticosteroides/administração & dosagem , Inibidores de Calcineurina/administração & dosagem , Humanos , Pomadas , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Tacrolimo/administração & dosagem
8.
Gastroenterol Hepatol ; 43(8): 457-463, 2020 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32646657

RESUMO

SARS-CoV-2 infection has produced a pandemic with serious consequences for our health care system. Although liver transplant patients represent only a minority of the population, the hepatologists who follow these patients have tried to coordinate efforts to produce a protocol the management of immunosuppression during SARS-CoV-2 infection. Although there are no solid studies to support general recommendations, experiences with other viral infections (hepatitis C, cytomegalovirus) suggest that management of immunosuppression without mycophenolate mofetil or m-Tor inhibitors (drugs that are also associated with leukopenia and lymphopenia) may be beneficial. It is also important to pay attention to possible drug interactions, especially in the case of tacrolimus, with some of the treatments with antiviral effect given in the context of COVID 19 (lopinavir/ritonavir, azithromycin). Finally, the immunosuppressive effect of immunomodulating drugs (tocilizumab and similar) administered to patients with severe lung disease should be taken into account. The mechanisms of action of the different immunosuppressive drugs are reviewed in this article, as well as their potential effect on SARS-CoV-2 infection, and suggests guidelines for the management of immunosuppression.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Imunossupressão/efeitos adversos , Imunossupressores/efeitos adversos , Transplante de Fígado , Pandemias , Pneumonia Viral/epidemiologia , Imunidade Adaptativa , Antivirais/farmacologia , Betacoronavirus/imunologia , Betacoronavirus/fisiologia , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/farmacologia , Inibidores de Calcineurina/uso terapêutico , Contraindicações de Medicamentos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Suscetibilidade a Doenças , Interações Medicamentosas , Everolimo/efeitos adversos , Everolimo/farmacologia , Everolimo/uso terapêutico , Glucocorticoides/efeitos adversos , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Imunidade Inata , Hospedeiro Imunocomprometido , Imunossupressão/métodos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/farmacologia , Ácido Micofenólico/uso terapêutico , Pneumonia Viral/imunologia , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/prevenção & controle , Sirolimo/efeitos adversos , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores
9.
Braz J Infect Dis ; 24(4): 365-367, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32603679

RESUMO

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can cause mild, moderate or severe disease (COVID-19). In severe disease, there is hyperinflammation causing severe symptoms. Severe COVID-19 is an immunological phenomenon, rather than a direct viral damage disease. Therapies for COVID-19 are all investigational therapies. In case of severe disease, treatment with a calcineurin inhibitor could be promising. In this article we explain the mechanisms of calcineurin inhibitor treatment for COVID-19, based on experiences seen in solid organ transplant recipients who suffered from COVID-19.


Assuntos
Inibidores de Calcineurina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , Humanos , Pandemias , Transplantados
10.
Expert Opin Pharmacother ; 21(15): 1813-1819, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32659126

RESUMO

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide. While there are presently a few case reports/series on COVID-19 amongst solid organ transplant (SOT) patients, there is no official guideline for the management of SOT patients. AREAS COVERED: The authors discuss the pharmacotherapeutic management of SOT patients during the COVID-19 outbreak and provide their expert perspectives. EXPERT OPINION: Prophylactic reduction of immunosuppression because of fear of COVID-19 is not suggested in SOT patients. With maintenance immunosuppressive regimens, corticosteroids can be continued during COVID-19. Continuing other immunosuppressive drugs with lowest effective dose/blood concentration is suggested for patients with mild to moderate COVID-19. Discontinuation of antimetabolites and perhaps inhibitors of mammalian target of rapamycin (mTOR) is suggested in moderate to severe COVID-19. Calcineurin inhibitors (CNIs) may be continued or substituted for mTOR inhibitors with lowest therapeutic concentrations in moderate to severe COVID-19. If continued in patients with COVID-19, therapeutic drug monitoring of CNIs/mTOR inhibitors and appropriate dose reduction is recommended in co-administration with protease inhibitors, hydroxychloroquine/chloroquine, or interleukin (IL)-1/IL-6 receptor antagonists. Complete blood count monitoring is recommended in patients who continue taking antimetabolites or mTOR inhibitors. Dose modification/avoidance should be considered for chloroquine, atazanavir, oseltamivir, ribavirin, anakinra, and Janus associated kinase inhibitors in patients with organ function impairment.


Assuntos
Infecções por Coronavirus/epidemiologia , Transplante de Órgãos/métodos , Pneumonia Viral/epidemiologia , Inibidores de Calcineurina/uso terapêutico , Humanos , Imunossupressão , Imunossupressores/uso terapêutico , Pandemias , Serina-Treonina Quinases TOR/antagonistas & inibidores
12.
Adv Clin Exp Med ; 29(5): 603-609, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32469166

RESUMO

BACKGROUND: Treatment with cyclosporine A (CsA), a calcineurin inhibitor, is effective in children with difficult idiopathic nephrotic syndrome (INS). Prolonged CsA treatment can result in several adverse effects, the most significant being nephrotoxicity (CsAN). The plasma and urine levels of the proteins annexin V (AnV) and uromodulin (UM) were investigated in order to assess their usefulness as indicators of early-stage CsAN. Uromodulin is considered a distal tubular damage marker. Annnexin V is present in the distal tubules. OBJECTIVES: To measure AnV in children with INS receiving CsA treatment and to assess the usefulness of this biomarker for monitoring CsAN and as an indicator of changes in the distal tubules of the nephron. MATERIAL AND METHODS: The prospective study included 30 patients with INS and 22 controls. Plasma and urinary AnV levels were measured 3 times: before CsA treatment, and after 6 and 12 months of therapy. The AnV levels were compared to those of UM. RESULTS: The urinary AnV and UM levels were significantly higher in the INS patients before CsA therapy in comparison to the reference group. A progressive increase of urinary AnV was observed after 6 and 12 months of therapy. Urinary UM only increased after 6 months. No significant correlations were found between plasma and urinary concentrations of the proteins studied. CONCLUSIONS: The increased urinary excretion of AnV in children with INS receiving CsA treatment may suggest its usefulness as an early marker of subclinical CsAN. Annexin V seems to be a more sensitive indicator of tubular damage in the course of CsA therapy than UM, though large, multicenter studies are needed.


Assuntos
Anexina A5/sangue , Anexina A5/urina , Inibidores de Calcineurina/uso terapêutico , Ciclosporina/uso terapêutico , Imunossupressores/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Síndrome Nefrótica/sangue , Síndrome Nefrótica/urina , Estudos Prospectivos , Resultado do Tratamento , Uromodulina/sangue , Uromodulina/urina
13.
Expert Opin Pharmacother ; 21(11): 1367-1376, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32401066

RESUMO

INTRODUCTION: Cardiac allograft vasculopathy (CAV) is a major limitation to long-term survival after heart transplantation. Its peculiar pathophysiology involves multifactorial pathways including immune-mediated and metabolic risk factors, which are associated with the development of specific pathological lesions. The often diffuse and chronic nature of the disease reduces the effectiveness of revascularization procedures, and pharmacological prevention of the disease is the sole therapeutic approach with some proven efficacy. AREAS COVERED: In this article, after briefly outlining the risk factors for CAV, the authors revise the potential pharmacological approaches that may reduce the burden of CAV. While several therapies have shown convincing efficacy in terms of CAV prevention diagnosed by coronary imaging, very few have been reported to improve prognosis with any meaningful level of evidence. EXPERT OPINION: The authors believe that a customizable approach is necessary for clinical practice given the currently available evidence. Furthermore, it is important, in the future, to address the glaring therapeutic gap of an effective treatment against donor-specific antibodies, whose effect on endothelial injury is currently one of the major mechanisms of CAV development and for which no pharmacological treatment is currently available.


Assuntos
Aloenxertos/efeitos dos fármacos , Inibidores de Calcineurina/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Transplante de Coração/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Imunossupressores/uso terapêutico , Aloenxertos/irrigação sanguínea , Aloenxertos/imunologia , Aloenxertos/patologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antioxidantes/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/patologia , Humanos , Inibidores da Agregação de Plaquetas/uso terapêutico , Fatores de Risco , Resultado do Tratamento
14.
Transplantation ; 104(4): 881-887, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32224815

RESUMO

BACKGROUND: Tacrolimus (TAC) is the most important agent for maintenance immunosuppression and prevention of immunologic injury to the renal allograft, yet there remains no consensus on how best to monitor drug therapy. Both high TAC intrapatient variability and low TAC time in therapeutic range (TTR) have been associated with risk of de novo donor-specific antibodies (dnDSA). In this study, we hypothesized that the risk associated with high TAC coefficient of variation (CV) is a result of low TAC TTR rather than the variability itself. METHODS: We analyzed the risk of dnDSA, acute rejection, or death-censored graft loss by non-dosed-corrected TAC CV and TAC TTR during the first posttransplant year in a cohort of 538 patients with a median follow-up period of 4.1 years. RESULTS: Patients with CV >44.2% and TTR <40% (high intrapatient variability and low TTR) had a high risk of dnDSA (adjusted OR = 4.93, 95% confidence interval = 2.02-12.06, P < 0.001) and death-censored graft loss by 5 years (adjusted HR = 4.00, 95% confidence interval = 1.31-12.24, P = 0.015) when compared with patients with CV >44.2% and TTR ≥40% (high intrapatient variability and optimal TTR), while the latter patients had similar risk to patients with CV <44.2% (lower intrapatient variability). CONCLUSIONS: These data suggest that previously reported immunologic risk associated with high TAC intrapatient variability is due to time outside of therapeutic range rather than variability in and of itself when evaluating absolute non-dose-corrected TAC levels irrespective of reason or indication.


Assuntos
Inibidores de Calcineurina/uso terapêutico , Monitoramento de Medicamentos , Rejeição de Enxerto/prevenção & controle , Antígenos HLA/imunologia , Imunossupressores/uso terapêutico , Isoanticorpos/sangue , Transplante de Rim , Tacrolimo/uso terapêutico , Adulto , Biomarcadores/sangue , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/sangue , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/sangue , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Tacrolimo/efeitos adversos , Tacrolimo/sangue , Fatores de Tempo , Resultado do Tratamento
15.
Am J Transplant ; 20(8): 2269-2275, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32337859

RESUMO

The fatality of novel coronavirus disease 2019 (COVID-19) is precipitously increased in patients with underlying comorbidities or elderly people. Kidney transplant (KT) recipients are one of the vulnerable populations for infection. COVID-19 infection in KT recipients might be a complicated and awkward situation, but there has been a lack of reports concerning this group. Herein, we demonstrated two distinct cases with different clinical progress. The first case was a 36-year-old man who underwent KT 3 years ago. He was diagnosed with COVID-19 expressing relevant symptoms. Following administration of lopinavir/ritonavir and hydroxychloroquine with reduced immunosuppressant, he recovered from COVID-19. However, the unexpected fluctuations in tacrolimus trough levels needed to be managed because of drug-to-drug interaction. The second case was developed in a 56-year-old man without any symptoms. He received a second KT from an ABO-incompatible donor 8 years ago. He was diagnosed with COVID-19 by screening due to exposure history. During the hospitalization period, the chest infiltrative lesion showed a wax and wane, but he successfully recovered by administration of hydroxychloroquine with azithromycin. These apparently different cases suggest that assertive screening and management could improve the clinical course. In addition, antiviral agents should be used cautiously, especially in patients on calcineurin inhibitors.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Falência Renal Crônica/complicações , Transplante de Rim , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Transplantados , Adulto , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Betacoronavirus , Inibidores de Calcineurina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Combinação de Medicamentos , Interações Medicamentosas , Humanos , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pandemias , Ritonavir/uso terapêutico , Tacrolimo/uso terapêutico
16.
Transplantation ; 104(5): 970-980, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32317615

RESUMO

BACKGROUND: Calcineurin inhibitors successfully control rejection of transplanted organs but also cause nephrotoxicity. This study, using a rhesus monkey renal transplantation model, sought to determine the applicability of a new immunomodulatory drug inhibiting the store-operated calcium release-activated calcium channel of lymphocytes to control transplant rejection without nephrotoxicity. METHODS: Animals underwent kidney transplantation and were treated with tacrolimus alone (n = 3), a CRACM1 inhibitor (PRCL-02) (n = 6) alone, or with initial tacrolimus monotherapy followed by gradual conversion at 3 weeks to PRCL-02 alone (n = 3). PRCL-02 was administered via a surgically inserted gastrostomy tube BID. RESULTS: Dose-related drug exposure in monkeys was established and renal transplants were then performed using PRCL-02 monotherapy. Oral dosing of PRCL-02 was well tolerated and resulted in suppressed T-cell proliferation in in vitro MLR comparable to animals in the tacrolimus control arm. Animals receiving tacrolimus monotherapy were e on day 100 without rejection. PRCL-02 monotherapy only marginally prolonged graft survival (MST = 13.16 d; group 2) compared with untreated controls. Animals treated initially with tacrolimus and converted to PRCL-02 monotherapy had a mean graft survival of 35.3 days which was prolonged compared with PRCL-02 monotherapy but not compared with the tacrolimus-treated group. Pharmacokinetic studies showed inconsistent drug exposures despite attempts to adjust dose and exposure which may have contributed to the rejections. CONCLUSIONS: We conclude that, in this nonhuman primate model of kidney transplantation, PRCL-02 demonstrated evidence of in vivo immunosuppressive activity but was inferior to tacrolimus treatment with respect to suppressing immune transplant rejection.


Assuntos
Canais de Cálcio Ativados pela Liberação de Cálcio/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressão/métodos , Transplante de Rim , Tacrolimo/uso terapêutico , Animais , Inibidores de Calcineurina/uso terapêutico , Modelos Animais de Doenças , Rejeição de Enxerto/diagnóstico , Macaca mulatta , Masculino , Transplante Homólogo , Resultado do Tratamento
18.
Ann Rheum Dis ; 79(6): 713-723, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32220834

RESUMO

OBJECTIVE: To update the 2012 EULAR/ERA-EDTA recommendations for the management of lupus nephritis (LN). METHODS: Following the EULAR standardised operating procedures, a systematic literature review was performed. Members of a multidisciplinary Task Force voted independently on their level of agreeement with the formed statements. RESULTS: The changes include recommendations for treatment targets, use of glucocorticoids and calcineurin inhibitors (CNIs) and management of end-stage kidney disease (ESKD). The target of therapy is complete response (proteinuria <0.5-0.7 g/24 hours with (near-)normal glomerular filtration rate) by 12 months, but this can be extended in patients with baseline nephrotic-range proteinuria. Hydroxychloroquine is recommended with regular ophthalmological monitoring. In active proliferative LN, initial (induction) treatment with mycophenolate mofetil (MMF 2-3 g/day or mycophenolic acid (MPA) at equivalent dose) or low-dose intravenous cyclophosphamide (CY; 500 mg × 6 biweekly doses), both combined with glucocorticoids (pulses of intravenous methylprednisolone, then oral prednisone 0.3-0.5 mg/kg/day) is recommended. MMF/CNI (especially tacrolimus) combination and high-dose CY are alternatives, for patients with nephrotic-range proteinuria and adverse prognostic factors. Subsequent long-term maintenance treatment with MMF or azathioprine should follow, with no or low-dose (<7.5 mg/day) glucocorticoids. The choice of agent depends on the initial regimen and plans for pregnancy. In non-responding disease, switch of induction regimens or rituximab are recommended. In pure membranous LN with nephrotic-range proteinuria or proteinuria >1 g/24 hours despite renin-angiotensin-aldosterone blockade, MMF in combination with glucocorticoids is preferred. Assessment for kidney and extra-renal disease activity, and management of comorbidities is lifelong with repeat kidney biopsy in cases of incomplete response or nephritic flares. In ESKD, transplantation is the preferred kidney replacement option with immunosuppression guided by transplant protocols and/or extra-renal manifestations. Treatment of LN in children follows the same principles as adult disease. CONCLUSIONS: We have updated the EULAR recommendations for the management of LN to facilitate homogenization of patient care.


Assuntos
Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Sociedades Médicas , Antirreumáticos/uso terapêutico , Azatioprina/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Quimioterapia Combinada , Europa (Continente) , Taxa de Filtração Glomerular , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Nefrite Lúpica/complicações , Nefrite Lúpica/patologia , Nefrite Lúpica/fisiopatologia , Ácido Micofenólico/uso terapêutico , Proteinúria/etiologia , Proteinúria/terapia
19.
J Pediatr ; 221: 138-144.e3, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32171558

RESUMO

OBJECTIVES: To characterize primary care providers' (PCPs) practice patterns for atopic dermatitis (AD) in children <2 years old and determine the need for AD guidelines for PCPs focused on this age group. STUDY DESIGN: This is a mixed-methods study consisting of a survey and a retrospective medical record review of PCP practices in the Chicago metropolitan area. The survey was analyzed using both quantitative and qualitative methods. RESULTS: In the survey (n = 52 respondents), PCPs reported management of AD is different in children <2 years compared with older children (88%). They were more likely to refer to a specialist (65%) and less likely to use high-potency topical corticosteroids (64%). In the chart review, PCP visits for children 2-5 years old (n = 50 914) vs those <2 years old (n = 71 913) for AD, older children had medium- and high-potency topical corticosteroids prescribed more frequently than younger children (0.66% vs 0.37%, P < .01 and .15% vs 0.05%, P < .01, respectively). In the subset of children <2 years of age who also were evaluated by a specialist (n = 109), medium- and high-potency topical corticosteroids were prescribed disproportionately at visits to providers in dermatology (57%) vs allergy (30%) vs pediatrics (15%) (P < .01). PCPs suggested that guidelines for this age group should include recommendations for preferred corticosteroids (39%), allergy management (35%), referral criteria (22%), and assessment of disease severity (11%). CONCLUSIONS: PCP management of AD in children <2 years is different from older children, with possible underuse of medium/high-potency topical corticosteroids. Clear guidelines for this age group are needed.


Assuntos
Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/epidemiologia , Pediatras , Padrões de Prática Médica/estatística & dados numéricos , Administração Tópica , Compostos de Boro/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Pré-Escolar , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Atenção Primária à Saúde , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários , Estados Unidos/epidemiologia
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