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1.
Plast Reconstr Surg ; 144(4): 619e-629e, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31568298

RESUMO

BACKGROUND: The authors hypothesize that ischemic preconditioning of the recipient site with deferoxamine will increase fat graft survival by enhancing angiogenesis in a rat model. METHODS: Cell viability, tube formation, and mRNA expression were measured in human umbilical vein endothelial cells treated with deferoxamine. A total of 36 rats were then used for an in vivo study. A dose of 100 mg/kg of deferoxamine was injected subcutaneously into the rat scalp every other day for five treatments. On the day after the final injection, the scalp skin was harvested from half the animals to evaluate the effects of deferoxamine on the recipient site. In the remaining animals, inguinal fat tissue was transplanted to the scalp. Eight weeks after transplantation, the grafts were harvested to evaluate the effects of deferoxamine preconditioning on fat graft survival. RESULTS: In human umbilical vein endothelial cells, treatment with a deferoxamine concentration higher than 400 µM decreased cell viability compared with the control (p = 0.002). Treatment with 100 and 200 µM deferoxamine increased endothelial tube formation (p = 0.001) and mRNA levels of angiogenesis-related factors (p = 0.02). Rat scalps treated with deferoxamine exhibited increased capillary neoformation (p = 0.001) and vascular endothelial growth factor protein expression (p = 0.024) compared with controls. Fat graft volume retention, capillary density (p < 0.001), and adipocyte viability (p < 0.001) in the grafted fat increased when the recipient site was preconditioned with deferoxamine. CONCLUSION: This study demonstrated that recipient site preconditioning with deferoxamine increases fat graft survival by inducing vascular endothelial growth factor and neovascularization.


Assuntos
Tecido Adiposo/transplante , Desferroxamina/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Precondicionamento Isquêmico/métodos , Neovascularização Fisiológica/efeitos dos fármacos , Fatores de Crescimento do Endotélio Vascular/biossíntese , Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos , Animais , Humanos , Masculino , Modelos Animais , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular
2.
Transplant Proc ; 51(8): 2615-2619, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31563241

RESUMO

BACKGROUND: Recently, a once-daily formulation of tacrolimus (Advagraf) was released in the Philippines. Studies have shown that these 2 formulations are bioequivalent at a 1:1 conversion. This study aims to determine the efficacy, safety, convertibility, and tacrolimus trough level of once-daily tacrolimus at the end of 6 months post transplant. METHODS: This is a randomized study among standard-risk primary kidney transplant patients performed at the National Kidney and Transplant Institute, Philippines. A total of 40 patients completed the 6-month follow-up. Patients in Group A who failed to meet the criteria for conversion to once-daily tacrolimus were considered to have reached the end of the study, while patients who satisfied the conversion criteria will be followed up for an additional 6 months. RESULTS: Baseline characteristics were similar in both groups. The area under the curve, maximum concentration, time to achieve the maximum concentration, and the coefficient of variation were similar. The twice-daily tacrolimus (Prograf) group patients had significantly higher mean tacrolimus trough levels than the Group B once-daily tacrolimus patients. An increase of a once-daily tacrolimus mean dose of 8% was required to achieve a therapeutic drug level post conversion. The graft and patient survival were 100%. There was no biopsy-proven acute rejection noted either both group. CONCLUSION: In conclusion, conversion from twice-daily tacrolimus to once-daily tacrolimus in kidney transplant in both de novo and converted patients after KT is safe, ensuring greater stability of drug blood concentrations than the standard form. The results also suggest an 8% increase when converting stable KT patients from twice-daily tacrolimus to once-daily tacrolimus.


Assuntos
Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/administração & dosagem , Transplante de Rim , Tacrolimo/administração & dosagem , Adulto , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Filipinas , Projetos Piloto , Equivalência Terapêutica
3.
Transplant Proc ; 51(8): 2624-2628, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31563242

RESUMO

INTRODUCTION: Mycophenolate mofetil has improved long-term outcomes of kidney transplantation. However, the impact of mycophenolic acid (MPA) trough level on the development of de novo donor-specific anti-HLA antibody (DSA) is unclear. We examined the relation between MPA trough level and de novo DSA development. METHOD: We retrospectively studied 617 kidney recipients whose MPA trough level and de novo DSA data were available. All patients underwent primary kidney transplant from living donors from 2008 to 2014, and were chronically treated with a calcineurin inhibitor, mycophenolate mofetil, and +/- steroids. They were equally divided into 4 groups according to the mean trough level of MPA (mMPA) at 1 year post-transplantation: Group 1, mMPA < 2.14 ng/mL (n = 152); Group 2, mMPA 2.14-2.83 ng/mL (n = 157); Group 3, mMPA 2.83-3.57 ng/mL (n = 153); and Group 4, mMPA ≥ 3.57 ng/mL (n = 155). The groups were compared by incidence rate of de novo DSA, graft survival rate, and renal function. RESULTS: The incidence rates of de novo DSA were 33.3% in Group 1, 23.7% in Group 2, 22.9% in Group 3, and 30.3% in Group 4 (P = .158). Although there was no significant difference in graft survival rates, a significant difference of renal functions was noted: the higher the renal function, the lower the MPA trough level. CONCLUSION: The mMPA trough level at 1 year post-transplantation was not statistically associated with the incidence rate of de novo DSA after kidney transplantation.


Assuntos
Soro Antilinfocitário/efeitos dos fármacos , Rejeição de Enxerto/prevenção & controle , Imunossupressores/farmacocinética , Transplante de Rim/efeitos adversos , Ácido Micofenólico/farmacocinética , Adulto , Anticorpos/imunologia , Soro Antilinfocitário/imunologia , Inibidores de Calcineurina/administração & dosagem , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Humanos , Transplante de Rim/métodos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
4.
Transplant Proc ; 51(8): 2643-2647, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31477420

RESUMO

BACKGROUND: The stable immunosuppressant level at the early period after kidney transplantation (KT) is one of the most important factors for the prognosis of KT. However, the extent of immunosuppression varies according to the policies of each KT center. We investigated the relationship between the clinical outcome and tacrolimus trough level (TTL) at the early post-transplant period. MATERIALS AND METHODS: We retrospectively analyzed medical records of patients who underwent KT between July 2007 and June 2016. We investigated TTLs at 3 months after KT. We evaluated the incidence of biopsy-proven acute rejection (BPAR), cytomegalovirus infection, and graft survival according to the TTLs. RESULTS: A total of 426 patients who received KT during the study period were enrolled. The mean age of KT recipients was 46.3 ± 11.5 years, and 55.5% of patients were men. The incidence of BPAR within 1 year after KT was significantly higher when TTLs at 3 months were less than 4.0 ng/mL (P = .020). Death-censored graft survival rates were significantly lower in KT recipients with BPAR and TTL less than 4.0 ng/mL (P < .001, P < .001, respectively). In multivariate analysis, BPAR and TTL less than 4.0 ng/mL at 3 months after KT were independent risk factors for graft failure. CONCLUSION: BPAR and TTL less than 4.0 ng/mL at 3 months after KT are important risk factors for allograft failure. Therefore, TTL should be kept at least 4.0 ng/mL or more at 3 months after KT to reduce the incidence of BPAR within 1 year after KT.


Assuntos
Rejeição de Enxerto/epidemiologia , Imunossupressão/métodos , Imunossupressores/farmacocinética , Transplante de Rim , Tacrolimo/farmacocinética , Adulto , Feminino , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Transplante Homólogo
5.
Transplant Proc ; 51(8): 2611-2614, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31474447

RESUMO

BACKGROUND: The clinical benefit of rabbit antithymocyte globulin (Thymoglobulin) compared with basiliximab for induction therapy in kidney transplant (KT) resulting from acute kidney injury (AKI) donors remains controversial. In cases of severe AKI, the degree of kidney injury is too great to reveal influence of different induction therapies on clinical outcomes. We aimed to compare clinical outcomes of Thymoglobulin and basiliximab induction therapy in KTs from deceased donors (DDs) with mild to moderate AKI. METHODS: We retrospectively studied 147 patients who received KTs from DDs between 2009 and 2017 in our center; 91 patients received kidneys from AKI donors. The AKI severity was classified based on the Acute Kidney Injury Network (AKIN) staging, and patients with AKIN stage 3 (43 patients) were excluded. Clinical outcomes were compared according to the type of induction therapy. RESULTS: Thymoglobulin and basiliximab induction groups showed no significant differences in demographic and baseline characteristics except donor age and follow-up period. The Thymoglobulin group had lower incidences of acute rejection and a trend toward a lower incidence of delayed graft function and better graft survival than the basiliximab group. There was no significant difference in BK infection rate; however, cytomegalovirus infection rate showed a trend toward a lower incidence in the basiliximab group. CONCLUSIONS: In cases of KT from AKIN stage 1 and 2 donors, Thymoglobulin showed better clinical outcomes than basiliximab, although it had a somewhat high rate of cytomegalovirus infection. It seems beneficial to use Thymoglobulin induction therapy in KTs from DDs with mild to moderate AKI.


Assuntos
Lesão Renal Aguda , Soro Antilinfocitário/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim , Doadores de Tecidos , Lesão Renal Aguda/etiologia , Adulto , Basiliximab/uso terapêutico , Infecções por Citomegalovirus/epidemiologia , Função Retardada do Enxerto/epidemiologia , Função Retardada do Enxerto/etiologia , Feminino , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Incidência , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/epidemiologia , Estudos Retrospectivos
6.
Transplant Proc ; 51(7): 2308-2311, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400977

RESUMO

BACKGROUND: This study aimed to determine whether de novo, prolonged-release tacrolimus- (PR-tacro) based immunosuppressive regimen affected graft and patient survival when compared to an immediate-release, twice-daily, tacrolimus- (IR-tacro) based regimen in kidney transplant recipients. We also aimed to determine the difference between the frequency of side effects, including diabetes control, in study groups. METHODS: A total of 115 standard risk kidney transplant recipients were enrolled in this single center, retrospective study. Fifty-two patients received PR-tacro and 63 patients received IR-tacro as a calcineurin inhibitor. The primary outcome measures included incidence of graft loss and delayed graft function (DGF), biopsy-proven acute rejection , graft and patient survival, and creatinine clearance. Secondary outcome measures included the incidence of non-adherence, drug-induced tremor; post-transplant diabetes mellitus diagnosis rate; and control of diabetes in pre-transplant diabetic patients. RESULTS: Baseline characteristics and mean tacrolimus trough levels were comparable between groups. Incidence of graft loss, DGF, and graft and patient survival were similar between groups (P > .05). Mean creatinine clearance level was also similar (P > .05). Mean serum levels of fasting glucose (P < .05) and A1C (P < .05) were lower in PR-tacro group when compared to IR-tacro group. Post-transplant diabetes mellitus diagnosis rate was also lower in PR-tacro group when compared to IR-tacro group (P = .040). CONCLUSION: This study suggests that there is no statistically significant difference between PR-tacro and IR-tacro in terms of patient and graft survival, DGF, and biopsy-proven acute rejection rates in kidney transplant recipients. Post-transplant diabetes mellitus frequency is lower in non-diabetic patients, and glucose metabolism control is better in diabetic patients.


Assuntos
Inibidores de Calcineurina/administração & dosagem , Rejeição de Enxerto/mortalidade , Imunossupressores/administração & dosagem , Transplante de Rim/mortalidade , Tacrolimo/administração & dosagem , Adulto , Função Retardada do Enxerto/etiologia , Feminino , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
7.
Transplant Proc ; 51(6): 2081-2098, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399186

RESUMO

Sphingosine-1-phosphate (S1P) is a biologically active sphingolipid that acts through the members of a family of 5 G protein-coupled receptors (S1P1 to S1P5). Among these, S1P1 is a major regulator of lymphocyte trafficking. Fingolimod, whose active metabolite, fingolimod phosphate, acts as a nonselective S1P-receptor agonist, exerts its immunomodulatory effect, at least in part, by regulating lymphocyte trafficking via downregulation of S1P1 expression on lymphocytes. Here, we describe the pharmacologic profile of a novel S1P1 agonist, ASP1126. ASP1126 preferentially activated S1P1 compared to S1P3 in rat and human guanosine-5'-(γ-thio)-triphosphate (GTPγS) assays. Oral single administration of ASP1126 decreased the number of peripheral lymphocytes and repeated dosing showed a cumulative effect on lymphopenia in both rats and monkeys. ASP1126 prolonged allograft survival in a rat heterotopic heart transplantation model in combination with a subtherapeutic dose of tacrolimus that was independent of drug-drug interactions. In addition, in nonhuman primate (NHP) renal transplantation, pretreatment with ASP1126 reduced not only the number of naive T cells and central memory T cells but also effector memory T cells in the peripheral blood, all of which could contribute to acute graft rejection and prolonged allograft survival in combination with tacrolimus. Further, we confirmed that ASP1126 has a broad ranging safety margin with respect to its effect on lung weight in rats and bradycardia in NHPs, which were the adverse events found in clinical studies of fingolimod. ASP1126 with improved safety profile has the potential to be an adjunct therapy in combination with tacrolimus in clinical transplantation.


Assuntos
Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/farmacologia , Lisofosfolipídeos/agonistas , Esfingosina/análogos & derivados , Aloenxertos/efeitos dos fármacos , Aloenxertos/metabolismo , Animais , Bradicardia/induzido quimicamente , Sinergismo Farmacológico , Humanos , Linfócitos/efeitos dos fármacos , Macaca fascicularis , Masculino , Ratos , Esfingosina/agonistas , Tacrolimo/farmacologia , Transplante Homólogo/métodos
8.
Transplant Proc ; 51(8): 2731-2734, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31447189

RESUMO

BACKGROUND: There is little evidence about whether mammalian target of rapamycin (mTOR) inhibitor could prevent post-kidney transplant (KT) urothelial carcinoma (UC) or not. The aim of this study is to analyze the role of mTOR inhibitor add-on in tacrolimus-based kidney transplant recipients. METHOD: The data were obtained from the Kaohsiung Chang Gung Memorial Hospital using the Chang Gung Research Database and retrospectively reviewed from January 2000 to December 2015. Patients then were categorized into 2 groups: group FK (more than 2-year tacrolimus [FK] prescription) and group FK + mTOR inhibitor (more than 2-year tacrolimus plus at least 6-month continued sirolimus prescription). The primary end point is post-KT UC development. The secondary end point is mTOR inhibitor add-on effect on renal function deterioration episode. RESULTS: There were 140 patients with tacrolimus-based immunosuppressant (group FK) and 82 patients with tacrolimus-based and add-on mTOR inhibitor regimen (group FK + mTOR inhibitor). The follow-up duration, sex distribution, and combined mycophenolate mofetil rate are similar in both groups. Younger age, lower tacrolimus trough level, lower UC incidence, and longer KT-to-UC interval were observed. Short- to intermediate-term results revealed noninferior graft outcome by creatinine level or creatinine deterioration. CONCLUSIONS: In our preliminary result, mTOR inhibitor add-on in patients with tacrolimus-based regimen revealed less post-KT UC occurrence. In addition, noninferior graft outcome was also observed. In Taiwan, a high UC prevalence area, mTOR inhibitor add-on strategy can be considered as a preventive strategy for UC after KT.


Assuntos
Carcinoma de Células de Transição/epidemiologia , Imunossupressores/uso terapêutico , Transplante de Rim , Complicações Pós-Operatórias/epidemiologia , Sirolimo/uso terapêutico , Adulto , Carcinoma de Células de Transição/etiologia , Carcinoma de Células de Transição/imunologia , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Hospedeiro Imunocomprometido , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/imunologia , Estudos Retrospectivos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Tacrolimo/uso terapêutico , Taiwan
9.
Transplant Proc ; 51(8): 2633-2636, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31447192

RESUMO

INTRODUCTION: The most effective immunosuppressant protocol in kidney transplantation (KT) is the combination of a calcineurin inhibitor, steroid, and mycophenolate mofetil (MMF) until now. However, MMF withdrawal (MW) is performed for many reasons, and the clinical course of the KT recipients after MW is not clearly known. The purpose of this study was to investigate the clinical outcomes of KT after MW. MATERIALS AND METHODS: We retrospectively analyzed the medical records of 626 KT recipients between 2000 and 2016. We evaluated the incidence of biopsy-proven acute rejection (BPAR), graft and patient survival rates, and risk factors related with graft failure. RESULTS: The proportion of MW was 33.2% (208 of 626 patients). The median time between KT and MW was 6.4 months (range, 3.2-32.1 months). The common causes of MW were infection (70.7%), hematologic abnormalities (9.1%), and gastrointestinal trouble (7.7%). The incidence of BPAR was significantly higher in the MW group compared with the MMF continuation group (27.4% vs 8.9%, respectively, P < .001). Death-censored graft survival and patient survival rates were significantly lower in the MW group compared with the MMF continuation group (P < .001; P < .001, respectively). In the multivariate analysis, BPAR after MW was an independent risk factor for graft failure (hazard ratio 6.058, 95% confidence interval, 3.172-11.569, P < .001). CONCLUSIONS: The incidence of rejection, graft failure, and patient mortality in KT were high after MW. Therefore, MW should be considered carefully.


Assuntos
Rejeição de Enxerto/mortalidade , Imunossupressores/administração & dosagem , Transplante de Rim , Ácido Micofenólico/administração & dosagem , Síndrome de Abstinência a Substâncias/mortalidade , Suspensão de Tratamento , Adulto , Inibidores de Calcineurina/administração & dosagem , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esteroides/administração & dosagem , Síndrome de Abstinência a Substâncias/etiologia , Resultado do Tratamento
10.
Transplant Proc ; 51(8): 2606-2610, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31439331

RESUMO

BACKGROUND: Antithymocyte globulin (ATG) is an induction therapy in kidney transplantation, but our knowledge about the relation between outcomes and ATG regimens is limited. We compared ATG effectiveness in kidney transplantation according to dosage and administration schedule. METHODS: Reports from 1970 until May 2018 in CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded were searched. We performed direct and indirect network meta-analysis using Bayesian models and generated rankings for ATG dosage and injection number variations by generation mixed treatment comparison.We compared ATG dose and schedule in kidney transplantation in relation to all-cause death, graft failure, antibody-mediated rejection, T-cell mediated rejection, biopsy-proven acute rejection, and bacterial and viral infection. RESULTS: Ten studies (N = 1065) were analyzed by forming 6 groups: ATG alternate doses, 9 mg/kg, 6 mg/kg, and 4.5 mg/kg; single dose, 6 mg/kg, and 4.5 mg/kg; and control. Compared to placebo, ATG regimen variations were not associated with significant differences in survival, viral infection, renal function, or graft survival. ATG regimens 9 and 4.5 mg alternate dosing tended to reduce biopsy-proven acute rejection but without statistical significance. According to the highest rank probability, the 9 mg alternate dosing group had the highest tendency for cytomegalovirus and bacterial infections but without statistical significance. CONCLUSIONS: The rejection frequency tended to be lower for the 9 and 4.5 mg alternate dosing groups. Infections occurred at a higher rate in the 9 mg alternate dosing group, but the differences in the risk of infection among the groups with different ATG regimens were not statistically significant.


Assuntos
Soro Antilinfocitário/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim , Meta-Análise em Rede , Adulto , Feminino , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade
11.
Cardiovasc Pathol ; 42: 59-63, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31351216

RESUMO

This article reviews the surgical considerations of cardiac allograft rejection after heart transplantation and describes current treatment modalities for the failing graft. Cardiac allograft rejection can be a moribund diagnosis, especially when it is acute and high grade. It is broadly categorized into hyperacute, acute cellular, and antibody-mediated rejection. Treatment includes a multitude of medical and immunomodulation therapies for graft recovery. Severe rejection requires mechanical circulatory support for hemodynamic stability to maintain end-organ function. Retransplantation for graft loss is the ultimate therapy; however, it portends poor outcomes.


Assuntos
Oxigenação por Membrana Extracorpórea , Rejeição de Enxerto/terapia , Sobrevivência de Enxerto/efeitos dos fármacos , Cardiopatias/terapia , Transplante de Coração/efeitos adversos , Coração Auxiliar , Imunossupressores/uso terapêutico , Oxigenação por Membrana Extracorpórea/efeitos adversos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/fisiopatologia , Cardiopatias/etiologia , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Humanos , Imunossupressores/efeitos adversos , Recuperação de Função Fisiológica , Reoperação , Fatores de Risco , Resultado do Tratamento
12.
Transplant Proc ; 51(8): 2637-2642, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349984

RESUMO

BACKGROUND: Mizoribine (MZR) has been developed as an immunosuppressant and is widely used in Asia. However, most studies on MZR have been performed in Japan, and there remains a lack of reports on long-term use in other countries. The purpose of this study is to evaluate the efficacy and safety of MZR's use in Korean kidney transplant recipients by observing their clinical courses and analyzing their long-term patent and graft survival rates. METHODS: We studied 129 subjects who had received MZR as a maintenance immunosuppressant since January 2000. Our analysis was based on the patients' medical records from January 2000 to December 2017. RESULTS: The overall survival rates of the kidney transplant recipients were 100% at 1 year, 99.1% at 5 years, 96.8% at 10 years, and 92.5% at 15 years. The graft survival rates were 100% at 1 year, 98.3% at 5 years, 93.2% at 10 years, and 82.2% at 15 years. There were differences in the recipient survival and graft survival rates according to the kidney donor and the use of renal replace therapy before transplant. There were no differences in the survival rates according to the MZR dose, the type of underlying disease, or other clinical factors. CONCLUSIONS: The use of low doses of MZR as a maintenance immunosuppressant could be an effective means of ensuring relatively good long-term patient and graft survival rates in cases of kidney transplant.


Assuntos
Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/administração & dosagem , Transplante de Rim/mortalidade , Ribonucleosídeos/administração & dosagem , Adulto , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Fatores de Tempo
13.
Plast Reconstr Surg ; 144(1): 70e-77e, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31246821

RESUMO

BACKGROUND: Random pattern skin flaps are applicable for reconstructing any defect in plastic surgery. However, they are difficult to apply because of necrosis. Sumatriptan, a selective 5-hydroxytryptamine 1b/1d agonist, is routinely used to offset acute migraine attacks. Recent studies have suggested that sumatriptan may induce vasodilation at lower concentrations. The authors' aim is to investigate the effect of sumatriptan on skin flap survival and the role of nitric oxide in this phenomenon. METHODS: Seventy-two male Sprague-Dawley rats were divided into eight groups. Increasing doses of sumatriptan (0.1, 0.3, and 1 mg/kg) were given intraperitoneally to three different groups after dorsal random pattern skin flaps were performed. To assess the exact role of 5-hydroxytryptamine 1b/1d receptors, GR-127935 was administered solely and with sumatriptan. N-ω-nitro-L-arginine methyl ester (L-NAME, a nonselective nitric oxide synthase inhibitor) was used to evaluate any possible involvement of nitric oxide in this study. All rats were examined 7 days later. RESULTS: The authors' results demonstrated that flap survival was increased by lower doses of sumatriptan compared to a control group for both 0.3 mg/kg (p = 0.03, mean difference = 32, SE = 8) and 0.1 mg/kg (p = 0.02, mean difference = 26, SE = 8). This protective effect was eliminated by coadministration of GR-127935 or N-ω-nitro-L-arginine methyl ester with sumatriptan. Histopathologic studies revealed a significant increase in capillary count and collagen deposition and a decreased amount of edema, inflammation, and degeneration. CONCLUSIONS: Sumatriptan in lower concentration increases skin flap survival by means of activation of 5-hydroxytryptamine 1b/1d receptors. This effect is mediated through the nitric oxide synthase pathway.


Assuntos
Sobrevivência de Enxerto/efeitos dos fármacos , Oxidiazóis/farmacologia , Piperazinas/farmacologia , Receptor 5-HT1B de Serotonina/administração & dosagem , Transplante de Pele , Sumatriptana/farmacologia , Retalhos Cirúrgicos , Vasodilatadores/farmacologia , Animais , Masculino , Óxido Nítrico/metabolismo , Ratos , Ratos Sprague-Dawley
14.
Saudi J Kidney Dis Transpl ; 30(3): 606-614, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249224

RESUMO

Cytomegalovirus (CMV) is one of opportunistic infections post solid organ transplant and remains a cause of morbidity and mortality. Mammalian target of rapamycin inhibitors has a theoretical antiviral advantage compared to conventional immunosuppression. The primary outcome was to assess the viremic response and kidney function in a cohort of kidney transplant recipients (KTRs) with difficult to manage CMV infection when converted to sirolimus. We retrospectively analyzed the outcome of substituting sirolimus for mycophenolate mofetil (MMF) or tacrolimus in 18 KTR with difficult to manage, resistant/recurrent CMV viremia unresponsive or intolerant of standard anti-CMV treatment, or immunosuppression reduction. Safety and feasibility of sirolimus conversion were assessed through studying CMV viral loads, creatinine levels, immunosuppression, antiviral therapy, kidney function, and acute rejection episodes before and after starting sirolimus as well as the sirolimus side effects. Data were collected from the hospital filing system. The Wilcoxon matched-pairs signed-rank test and Friedman test were used for statistical analysis. The area under the curve for Log10 CMV viral load (log10 copies/ml) was significantly higher before than after the sirolimus switch (P = 0.0156). The median number of days on antiviral treatment was reduced after conversion to sirolimus [48 days (0-95); vs. 68 days (21-146)]. Acute rejection occurred more commonly before than after starting sirolimus [n =5 (27.7%) vs. n = 2 (11.1%)]. Median serum creatinine before conversion to sirolimus was 175.5 µmol/L (79-243), and showed no deterioration three months and one year after conversion [148 (69-271) and 162.5 (69-287) µmol/L, respectively, P = 0.002]. The use of sirolimus, often alongside tacrolimus and after discontinuation of MMF, is a useful strategy in treating recurrent CMV viremia without provoking rejection.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Infecções Oportunistas/tratamento farmacológico , Sirolimo/uso terapêutico , Adulto , Idoso , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Substituição de Medicamentos , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Infecções Oportunistas/virologia , Recidiva , Estudos Retrospectivos , Fatores de Risco , Sirolimo/efeitos adversos , Tacrolimo/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
15.
Saudi J Kidney Dis Transpl ; 30(3): 640-647, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249228

RESUMO

The outcome of long-term kidney allograft is extremely important. The present study aimed to discern the factors affecting long-term kidney allograft survival, including the type of donation and the use of extended criteria donors. Seven hundred and thirty-seven kidney transplant alone patients entered this retrospective cross-sectional study. The impact of different factors on death-censored long-term kidney allograft survival was evaluated. The Cox proportional survival model was employed to identify these factors. A value of P < 0.05 was considered statistically significant. The data were analyzed using IBM Statistical Package for the Social Sciences version 19.0. The study was conducted at the Mashhad University of Medical Sciences, Mashhad, Iran. In comparison with living kidney donations, both nontraumatic and traumatic brain death cadaveric kidney donations showed statistically significant inferior graft survival. Furthermore, the Kaplan-Meier survival analysis showed better durability of living kidney donations in comparison with traumatic and nontraumatic deceased donors (Log-rank test value = 0.001). Patients with delayed graft function (DGF) had a significantly shorter long-term death censured long-term graft survival in comparison with those without this complication. The Cox proportional models showed that DGF occurrence and the type of donation play a statistically significant role in long-term kidney graft survival. In addition, regarding graft survival, there was no difference between standard criteria and extended criteria donors. The occurrence of DGF and living or deceased types of donations have a significant effect on long-term kidney allograft survival.


Assuntos
Função Retardada do Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Adulto , Idoso , Estudos Transversais , Função Retardada do Enxerto/mortalidade , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/mortalidade , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
16.
Saudi J Kidney Dis Transpl ; 30(3): 655-662, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249230

RESUMO

Although the outcomes of ABO-incompatible (ABOi) kidney transplant recipients are quite favorable, these patients are at increased risk of early antibody-mediated rejection (AMR) and graft loss. Some studies have also shown high mortality in the ABOi group mainly due to increased risk of infections. The AMR rates have been reported anywhere from <10% to >50% in the literature. The outcomes of the ABOi kidney transplants in the Saudi population are not known. In this study, we aimed to determine the graft and patient survival in ABOi kidney transplant recipients in the Saudi population. We included all adult patients who underwent ABOi transplantation between 2007 and 2016. All patients received rituximab, therapeutic plasma exchange, thymoglobulin, intravenous antibiotics, and intravenous immunoglobulin. The maintenance immunosuppression was prednisone, mycophenolate mofetil, and tacrolimus. The data were collected from a prospectively maintained database. A total of 77 patients were included in the study. The most common blood group mismatch was A to O (44.2%), followed by B to O (26.0%) and A to B (16.9%). In the 1st year, 17% of patients developed acute cellular rejection and AMR occurred in 7.8% of patients. Two patients were diagnosed with BK nephropathy. In the 1st year, urinary tract infection occurred in 25 (32.5%) patients. No patient was diagnosed severe viral or fungal infection. In the 1st year, four grafts were lost (graft survival of 94.8%); all grafts were lost within two weeks, three due to AMR and one due to technical reason. One year patient survival was 100%. In this study of ABOi kidney transplant recipients, we observed low risks of infectious complications with excellent patient and graft survival. Our immunosuppressive protocol can be considered safe.


Assuntos
Sistema do Grupo Sanguíneo ABO/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Histocompatibilidade , Imunossupressores/uso terapêutico , Transplante de Rim , Adulto , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Masculino , Infecções Oportunistas/imunologia , Fatores de Risco , Arábia Saudita , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
17.
Saudi J Kidney Dis Transpl ; 30(3): 686-693, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249234

RESUMO

Nonadherence to immunosuppressant medications leading onto poor graft outcome is frequent among renal transplant recipients. In this study, we sought to assess the prevalence and correlates of nonadherence to immunosuppressants and its impact on graft function. A singlecenter, retrospective cum cross-sectional study of renal transplant recipients of age >18 years and who had completed at least six months after transplantation was performed. Nonadherence was assessed based on the Immunosuppressant Therapy Adherence Scale questionnaire. Factors attributed to nonadherence were assessed based on the Immunosuppressant Therapy Barriers Scale (ITBS) questionnaire. Social, economic, demographic data, and all transplant related information were recorded. Two hundred and seventy-nine patients were included in the study, of whom 78% were male. Median follow-up period was 46 months (interquartile range - 24 months to 82 months). Seventy-four patients (26.5%) admitted nonadherence to immunosuppressants. The nonadherence was significantly related to the male gender, late acute rejection episodes, rise in serum creatinine from > 0.5 mg/dL from nadir level, lower blood levels of calcineurin inhibitor, and higher ITBS scores. Refill rates and use of alarm reminders were not significantly associated with better adherence.


Assuntos
Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Adesão à Medicação , Adulto , Estudos Transversais , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/efeitos adversos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
18.
J Reconstr Microsurg ; 35(7): 529-540, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31042803

RESUMO

BACKGROUND: The use of vasopressors in free flap surgery has traditionally been avoided due to the presumed risk of pedicle vasospasm leading to flap failure. However, there is a lack of strong clinical evidence to suggest that their administration during microvascular surgery is absolutely contraindicated. The aim of this study is to clarify the impact of perioperative vasopressor use on free flap outcomes. METHODS: A systematic review was performed of all English-language articles that have compared free flap outcomes between patients who received vasopressors and those who did not. The outcome measures were total flap failure, pedicle thrombosis, and overall flap complications. Meta-analysis was performed using Mantel-Haenszel fixed-effects and DerSimonian and Laird random-effects models. RESULTS: From a total of 130 citations, 14 studies representing 8,653 cases were analyzed. Majority of these did not find any negative effects of vasopressor use irrespective of dose, timing of administration, and method of delivery. Meta-analysis demonstrated that vasopressors were associated with less total flap failure overall (odds ratio, [OR]: 0.71, p = 0.05) and less pedicle thrombosis in head and neck reconstruction specifically (OR: 0.58, p = 0.02). Flap complication rates were similar across all defect types (OR: 0.97, p = 0.81) but appeared to be increased in breast reconstruction (OR: 1.46, p = 0.01). CONCLUSION: Perioperative vasopressor administration does not appear to be as detrimental to free flap survival as has been previously feared. Their role in optimizing hemodynamic stability may have a more beneficial effect on overall flap perfusion and in minimizing the complications of iatrogenic fluid overload.


Assuntos
Retalhos de Tecido Biológico/irrigação sanguínea , Vasoconstritores/uso terapêutico , Sobrevivência de Enxerto/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos , Complicações Pós-Operatórias/prevenção & controle
19.
Ther Drug Monit ; 41(3): 308-316, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31083041

RESUMO

BACKGROUND: Monitoring and maintaining a stable tacrolimus trough level is essential because of its narrow therapeutic window and considerable fluctuation in the early phase after kidney transplantation. However, optimal tacrolimus exposure early after transplantation remains unclear among Chinese patients. METHODS: In this propensity score-matched cohort study, we thoroughly investigated the association between tacrolimus trough level at the first month and acute rejection (AR) as well as infection within the first year after kidney transplantation. RESULTS: In a first step, a total of 1415 patients were divided into 3 groups according to the receiver operating characteristic curve: low-level group (410 patients with a tacrolimus trough level <5.35 ng/mL at the first month), median-level group (466 patients with a tacrolimus trough level from 5.35 to 7.15 ng/mL), and high-level group (539 patients with a tacrolimus trough level >7.15 ng/mL). Ultimately, 363 and 459 pairs of cases were enrolled by using 2 propensity score matches between low- and median-level groups and between high- and median-level groups, respectively. Compared with patients in the low-level group, patients in the median-level group had lower risk of AR without increased incidence of infection (AR, 12.4% versus 5.7%, P = 0.02; infection, 13.2% versus 13.2%, P = 1.00 for low- and median-level groups, respectively) within the first year. Compared with patients in the high-level group, patients in the median-level group had lower incidence of infection without the growing risk of AR (infection, 17.6% versus 12.2%, P = 0.021; AR, 4.6% versus 5.4%, P = 0.545 for high- and median-level groups, respectively) within the first year. Multilogistic analysis showed that tacrolimus trough levels were an independent factor for AR (odds ratio, 0.749, 95% confidence interval, 0.632-0.888, P = 0.001). Tacrolimus trough levels were also associated with infection (odds ratio 1.110, 95% confidence interval, 1.013-1.218, P = 0.001). Serum creatinine levels were similar among groups. No difference was found in 1-, 3-, and 5-year graft survival and patient survival among groups. CONCLUSIONS: The tacrolimus trough level maintained between 5.35 and 7.15 ng/mL at the first posttransplant month may prevent AR without increasing the incidence of infection within the first year after living kidney transplantation among Chinese patients.


Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Tacrolimo/sangue , Tacrolimo/uso terapêutico , Adulto , Estudos de Coortes , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão
20.
PLoS One ; 14(5): e0216300, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31136582

RESUMO

Calcineurin inhibitors (CNI), the cornerstone of immunosuppression after transplantation are implicated in nephrotoxicity and allograft dysfunction. We hypothesized that combined low doses of CNI and Everolimus (EVR) may result in better graft outcomes and greater tolerogenic milieu. Forty adult renal transplant recipients were prospectively randomized to (steroid free) low dose Tacrolimus (TAC) and EVR or standard dose TAC and Mycophenolate (MMF) after Alemtuzumab induction. Baseline characteristics were statistically similar. EVR levels were maintained at 3-8 ng/ml. TAC levels were 4.5±1.9 and 6.4±1.5 ng/ml in the TAC+EVR and TAC+MMF group respectively. Follow up was 14±4 and 17±5 months respectively and included protocol kidney biopsies at 3 and 12 months post-transplantation. Rejection-rate was lower in the TAC+EVR group. However patient and overall graft survival, eGFR and incidence of adverse events were similar. TAC+EVR induced expansion of CD4+CD25hiFoxp3+ regulatory T cells as early as 3 months and expansion of IFN-γ+CD4+CD25hiFoxp3+ regulatory T cells at 12 months post-transplant. Gene expression profile showed a trend toward decreased inflammation, angiogenesis and connective tissue growth in the TAC+EVR Group. Thus, greater tolerogenic mechanisms were found to be operating in patients with low dose TAC+EVR and this might be responsible for the lower rejection-rate than in patients on standard dose TAC+MMF. However, further studies with longer follow up and evaluating impact on T regulatory cells are warranted.


Assuntos
Everolimo/administração & dosagem , Transplante de Rim/métodos , Ácido Micofenólico/administração & dosagem , Tacrolimo/administração & dosagem , Adolescente , Adulto , Quimioterapia Combinada/métodos , Feminino , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/farmacologia , Masculino , Pessoa de Meia-Idade , Transplantados , Resultado do Tratamento , Adulto Jovem
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