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1.
J Crit Care ; 67: 126-131, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34768173

RESUMO

BACKGROUND: We compared filter survival and citrate-induced complications during continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in COVID-19 and Non-COVID-19 patients. METHODS: In this retrospective study we included all consecutive adult patients (n = 97) treated with RCA-CRRT. Efficacy and complications of RCA-CRRT were compared between COVID-19 and Non-COVID-19 patients. RESULTS: Mean filter run-time was significantly higher in COVID-19 patients compared to Non-COVID-19 patients (68.4 (95%CI 67.0-69.9) vs. 65.2 (95%CI 63.2-67.2) hours, respectively; log-rank 0.014). COVID-19 patients showed significantly higher activated partial thromboplastin time (aPTT) throughout the CRRT due to intensified systemic anticoagulation compared to Non-COVID-19 patients (54 (IQR 45-61) vs. 47 (IQR 41-58) seconds, respectively; p < 0.001). A significantly higher incidence of metabolic alkalosis, hypercalcemia and hypernatremia, consistent with reduced filter patency and citrate overload, was observed in COVID-19 patients compared to Non-COVID-19 patients (19.1% vs. 12.7%, respectively; p = 0.04). These metabolic disarrangements were resistant to per-protocol adjustments and disappeared after replacement of the CRRT-filter. CONCLUSIONS: RCA-CRRT in COVID-19 patients with intensified systemic anticoagulation provides an adequate filter lifespan. However, close monitoring of the acid-base balance appears warranted, as these patients tend to develop reduced filter patency leading to a higher incidence of citrate overload and metabolic disturbances. TRIAL REGISTRATION (LOCAL AUTHORITY): EA1/285/20 (Ethikkommission der Charité - Universitätsmedizin Berlin); date of registration 08.10.2020.


Assuntos
COVID-19 , Terapia de Substituição Renal Contínua , Anticoagulantes/efeitos adversos , Citratos , Ácido Cítrico/efeitos adversos , Estado Terminal , Humanos , Estudos Retrospectivos , SARS-CoV-2
2.
Nephrol Dial Transplant ; 37(5): 973-981, 2022 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-34665258

RESUMO

BACKGROUND: The most common definition of delayed graft function (DGF) relies on dialysis during the first week post-transplant and does not consider DGF severity. The impact of DGF severity on long-term graft outcome remains controversial. METHODS: We analysed 627 deceased-donor kidney transplant recipients (KTRs) transplanted in 2005-2015 at our centre for DGF severity, associated risk factors and long-term consequences of DGF. RESULTS: We found 349 (55.7%) KTRs with DGF, which were classified into four groups according to DGF duration (0-1, 2-7, 8-14, >14 days) and were compared with KTR with no DGF. A longer duration of DGF was associated with progressive worsening of 10-year death-censored graft survival {no DGF: 88.3% [95% confidence interval (CI) 82.4-94.2]; 0-1 day: 81.3% [95% CI 68.2-94.4], 2-7 days: 61.5% [95% CI 43.1.1-79.9], 8-14 days: 66.6% [95% CI 47.4-85.8], >14 days: 51.2% [95% CI 33-69.4]; P < 0.001}. In kidneys with a Kidney Donor Profile Index (KDPI) ≥85%, all DGF severity groups demonstrated reduced graft survival. However, in the <85% KDPI kidneys, only >14 days DGF duration showed worse outcomes. CONCLUSIONS: DGF had a duration-dependent effect on graft survival, which varied depending on the KDPI. Of note, 0- to 1-day DGF showed comparable results to no DGF in the whole cohort.


Assuntos
Função Retardada do Enxerto , Transplante de Rim , Função Retardada do Enxerto/etiologia , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos
3.
J Clin Med ; 10(23)2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34884335

RESUMO

To evaluate the outcomes of kidney transplantations (KTs) in the Eurotransplant Senior Program (ESP) with a focus on the very old, defined as recipients ≥75 years. This retrospective clinical study included 85 patients, who under the ESP protocol underwent deceased donor kidney transplantation from January 2010 to July 2018 at the Charité-Universitätsmedizin Berlin in Germany. Recipients were divided in three age groups, i.e., Group 65-69, Group 70-74, Group ≥75, and compared. Prognostic risk factors for short and long-term outcomes of kidney transplantations were investigated. Graft survival at 1 and 5 years were respectively 90.7% and 68.0% for group 65-69, 88.9% and 76.2% for Group 70-74, and 100% and 71.4% for Group ≥75. Patient survival at 1 and 5 years were respectively 92.9% and 68.0% for Group 65-69, 85.7% and 61.5% for Group 70-74 and 100% and 62.5% for Group ≥75. Serum creatinine did not significantly differ between the three groups, with the exception of serum creatinine at 1 year. Increased recipient age and prolonged time on dialysis correlated with increased occurrence of postoperative complication. An increase in BMI, pretransplant diabetes mellitus and prolonged time on dialysis correlated with the occurrence of delayed graft function (DGF). History of smoking was identified as an independent risk factor for events of rejection. Increased human leukocyte antigen mismatches (HLA-MM) and prolonged cold ischemia time (CIT) correlated with higher rates of intensive care unit (ICU) treatment. This study supports kidney transplantations for the very old. End-stage renal disease (ESRD) patients ≥75 years of age who underwent kidney transplantation experienced comparable results to their younger counterparts. A comprehensive evaluation of ESRD patients with consideration of prognostic risk factor is the most suitable mean of identifying adequate kidney transplant candidates.

4.
Circulation ; 144(14): 1133-1144, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34474590

RESUMO

BACKGROUND: Acute kidney injury (AKI) affects up to 30% of patients undergoing cardiac surgery, leading to increased in-hospital and long-term morbidity and mortality. Teprasiran is a novel small interfering RNA that temporarily inhibits p53-mediated cell death that underlies AKI. METHODS: This prospective, multicenter, double-blind, randomized, controlled phase 2 trial evaluated the efficacy and safety of a single 10 mg/kg dose of teprasiran versus placebo (1:1), in reducing the incidence, severity, and duration of AKI after cardiac surgery in high-risk patients. The primary end point was the proportion of patients who developed AKI determined by serum creatinine by postoperative day 5. Other end points included AKI severity and duration using various prespecified criteria. To inform future clinical development, a composite end point of major adverse kidney events at day 90, including death, renal replacement therapy, and ≥25% reduction of estimated glomerular filtration rate was assessed. Both serum creatinine and serum cystatin-C were used for estimated glomerular filtration rate assessments. RESULTS: A total of 360 patients were randomly assigned in 41 centers; 341 dosed patients were 73±7.5 years of age (mean±SD), 72% were men, and median European System for Cardiac Operative Risk Evaluation score was 2.6%. Demographics and surgical parameters were similar between groups. AKI incidence was 37% for teprasiran- versus 50% for placebo-treated patients, a 12.8% absolute risk reduction, P=0.02; odds ratio, 0.58 (95% CI, 0.37-0.92). AKI severity and duration were also improved with teprasiran: 2.5% of teprasiran- versus 6.7% of placebo-treated patients had grade 3 AKI; 7% teprasiran- versus 13% placebo-treated patients had AKI lasting for 5 days. No significant difference was observed for the major adverse kidney events at day 90 composite in the overall population. No safety issues were identified with teprasiran treatment. CONCLUSIONS: The incidence, severity, and duration of early AKI in high-risk patients undergoing cardiac surgery were significantly reduced after teprasiran administration. A phase 3 study with a major adverse kidney event at day 90 primary outcome that has recently completed enrollment was designed on the basis of these findings (NCT03510897). Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02610283.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Cardiopatias/tratamento farmacológico , Cardiopatias/cirurgia , RNA Interferente Pequeno/uso terapêutico , Idoso , Método Duplo-Cego , Feminino , Cardiopatias/complicações , Humanos , Masculino , RNA Interferente Pequeno/farmacologia
5.
Res Rep Urol ; 13: 495-499, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34285889

RESUMO

PURPOSE: Focal segmental glomerulosclerosis (FSGS) is a common cause for end-stage renal disease that can recur in the graft after kidney transplantation. The incidence of FSGS recurrence is reported in up to 47% of patients, predisposing those to possible poorer transplantation outcomes. Hence, we examined the incidence of FSGS recurrence and the effect on graft outcome in our patient cohort of living donor kidney transplantations (LDKT). PATIENTS AND METHODS: We analyzed 194 adult patients who received a LDKT between 2011 and 2017 of which 22 (11%) had FSGS as underlying disease. Demographic data and clinical outcomes, especially regarding recurrence of FSGS, were evaluated. RESULTS: FSGS recurrence was identified in three (14%) patients within three months after transplantation, of whom two patients (9%) lost their graft. There was no significant difference in graft survival comparing FSGS to other reasons for end-stage renal disease. CONCLUSION: Incidence of FSGS recurrence in the present patient cohort was within the range reported in the literature and comparatively low. Our data support LDKT as a treatment option in patients with end-stage renal disease due to FSGS.

6.
Sci Rep ; 11(1): 10678, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-34021219

RESUMO

With an urgent need for bedside imaging of coronavirus disease 2019 (COVID-19), this study's main goal was to assess inter- and intraobserver agreement in lung ultrasound (LUS) of COVID-19 patients. In this single-center study we prospectively acquired and evaluated 100 recorded ten-second cine-loops in confirmed COVID-19 intensive care unit (ICU) patients. All loops were rated by ten observers with different subspeciality backgrounds for four times by each observer (400 loops overall) in a random sequence using a web-based rating tool. We analyzed inter- and intraobserver variability for specific pathologies and a semiquantitative LUS score. Interobserver agreement for both, identification of specific pathologies and assignment of LUS scores was fair to moderate (e.g., LUS score 1 Fleiss' κ = 0.27; subpleural consolidations Fleiss' κ = 0.59). Intraobserver agreement was mostly moderate to substantial with generally higher agreement for more distinct findings (e.g., lowest LUS score 0 vs. highest LUS score 3 (median Fleiss' κ = 0.71 vs. 0.79) or air bronchograms (median Fleiss' κ = 0.72)). Intraobserver consistency was relatively low for intermediate LUS scores (e.g. LUS Score 1 median Fleiss' κ = 0.52). We therefore conclude that more distinct LUS findings (e.g., air bronchograms, subpleural consolidations) may be more suitable for disease monitoring, especially with more than one investigator and that training material used for LUS in point-of-care ultrasound (POCUS) should pay refined attention to areas such as B-line quantification and differentiation of intermediate LUS scores.


Assuntos
COVID-19/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Sistemas Automatizados de Assistência Junto ao Leito , SARS-CoV-2 , COVID-19/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Variações Dependentes do Observador , Estudos Prospectivos , Ultrassonografia
7.
Transpl Int ; 34(4): 732-742, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33527467

RESUMO

The number of patients returning to dialysis after graft failure increases. Surprisingly, little is known about the clinical and immunological outcomes of this cohort. We retrospectively analyzed 254 patients after kidney allograft loss between 1997 and 2017 and report clinical outcomes such as mortality, relisting, retransplantations, transplant nephrectomies, and immunization status. Of the 254 patients, 49% had died 5 years after graft loss, while 27% were relisted, 14% were on dialysis and not relisted, and only 11% were retransplanted 5 years after graft loss. In the complete observational period, 111/254 (43.7%) patients were relisted. Of these, 72.1% of patients were under 55 years of age at time of graft loss and only 13.5% of patients were ≥65 years. Age at graft loss was associated with relisting in a logistic regression analysis. In the complete observational period, 42 patients (16.5%) were retransplanted. Only 4 of those (9.5%) were ≥65 years at time of graft loss. Nephrectomy had no impact on survival, relisting, or development of dnDSA. Patients after allograft loss have a high overall mortality. Immunization contributes to long waiting times. Only a very limited number of patients are retransplanted especially when ≥65 years at time of graft loss.


Assuntos
Sobrevivência de Enxerto , Transplante de Rim , Rejeição de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Reoperação , Estudos Retrospectivos , Fatores de Risco
8.
Curr Rev Clin Exp Pharmacol ; 16(4): 357-368, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33588739

RESUMO

BACKGROUND/OBJECTIVE: Tacrolimus HEXAL®/Crilomus® is an approved generic immunosuppressant for the prevention and treatment of rejection following renal transplantation. For safe and socioeconomically efficient conversion of the innovator into a generic formulation, high- -quality data are necessary, in view of the different and country-specific comorbidities and pharmacokinetics in kidney transplant recipients. PATIENTS AND METHODS: From 2014 to 2017, we enrolled 32 kidney transplant recipients, receiving newly prescribed Tacrolimus HEXAL®/Crilomus® in 5 German centers. Efficacy and safety data were collected over 6-8 months and retrospectively compared to the period prior to conversion. RESULTS: The mean tacrolimus trough level was 4.91 ng/mL Standard Deviation (SD) (SD ±1.7) before and 5.06 ng/mL (SD ±1.97) after conversion. Mean tacrolimus trough concentration-dose-ratio (+/- SD) was 187.1 ng/mL/mg/kg/day (SD 99.2) for the reference and 205.1 ng/mL/mg/kg/day (SD 133) for the generic product, resulting in a non-significant difference of 18.0 ng/mL/mg/kg/day (SD 71.8) (p=0.84, Wilcoxon V=180). Overall, dosing had to be changed in 4 (14.8%) patients. Graft function remained stable and no rejections occurred. CONCLUSION: In conclusion, conversion to the generic tacrolimus formulation can be considered safe and feasible in long-term kidney transplant recipients in Germany. As suggested by guidelines, vigilant therapeutic drug monitoring is recommended to account for possible tacrolimus concentration variability on the individual patient level.


Assuntos
Transplante de Rim , Tacrolimo , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Tacrolimo/efeitos adversos , Transplantados
9.
J Clin Med ; 9(9)2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32887366

RESUMO

The collection of lymphatic fluids (lymphoceles) is a frequent adverse event following renal transplantation. A variety of surgical and medical factors has been linked to this entity, but reliable data on risk factors and long-term outcomes are lacking. This retrospective single-center study included 867 adult transplant recipients who received a kidney transplantation from 2006 to 2015. We evaluated for patient and graft survival, rejection episodes, or detectable donor-specific antibodies (dnDSA) in patients with identified lymphoceles in comparison to controls. We identified 305/867 (35.2%) patients with lymphocele formation, of whom 72/867 (8.3%) needed intervention. Multivariate analysis identified rejection episode as an independent risk factor (OR 1.61, CI 95% 1.17-2.21, p = 0.003) for lymphocele formation, while delayed graft function was independently associated with symptomatic lymphoceles (OR 1.9, CI 95% 1.16-3.12, p = 0.011). Interestingly, there was no difference in detectable dnDSA between groups with a similar graft and patient survival in all groups after 10 years. Lymphoceles frequently occur after transplantation and were found to be independently associated with rejection episodes, while symptomatic lymphoceles were associated with delayed graft function in our cohort. As both are inflammatory processes, they might play a causative role in the formation of lymphoceles. However, development or intervention of lymphoceles did not lead to impaired graft survival in the long-term.

10.
BMC Nephrol ; 20(1): 36, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30717681

RESUMO

BACKGROUND: Only a few prospective trials exist regarding the use of novel direct-acting antiviral agents (DAAs) in kidney transplant recipients (KTR) with chronic hepatitis C virus (HCV) infection. METHODS: This prospective single-center trial evaluated treatment with daclatasvir (DCV) and sofosbuvir (SOF) over 12 weeks in 16 adult chronic HCV infected KTR and eGFR > 30 ml/min/1.73m2. Primary endpoint was sustained virological response 12 weeks after end of therapy (SVR12). Beside baseline liver biopsy, hepatic function and glucose metabolism were regularly assessed. RESULTS: Four of 16 study patients had previously failed interferon-based HCV treatment. Liver biopsy showed mostly moderate fibrosis score before therapy with DCV/SOF was initiated at a median of 10.3 years after transplantation. In total, 15 of 16 KTR achieved SVR12. One patient showed early viral relapse because of resistance-associated variants (RAVs) in the HCV NS5A region. Rescue treatment with SOF/velpatasvir/voxilaprevir resulted in SVR12. DAAs treatment led to significant improvement of liver metabolism and glucose tolerance accompanied with no therapy-associated major adverse events and excellent tolerability. CONCLUSIONS: Our study demonstrates safety, efficacy and functional benefit of DCV/SOF treatment in KTR with chronic HCV infection. We provide data on rescue strategies for treatment failures due to present RAVs and amelioration of hepatic function and glucose tolerance. TRIAL REGISTRATION: Registry name: European Clinical Trials Register; Trial registry number (Eudra-CT): 2014-004551-32 , Registration date: Aug 28th 2015.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Imidazóis/uso terapêutico , Transplante de Rim , Sofosbuvir/uso terapêutico , Viremia/tratamento farmacológico , Adulto , Idoso , Ácidos Aminoisobutíricos , Antivirais/administração & dosagem , Biópsia por Agulha , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/uso terapêutico , Carbamatos/administração & dosagem , Carbamatos/farmacologia , Carbamatos/uso terapêutico , Ciclopropanos , Quimioterapia Combinada , Feminino , Intolerância à Glucose/induzido quimicamente , Hepacivirus/efeitos dos fármacos , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Lactamas Macrocíclicas , Leucina/análogos & derivados , Fígado/patologia , Compostos Macrocíclicos/administração & dosagem , Compostos Macrocíclicos/farmacologia , Compostos Macrocíclicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prolina/análogos & derivados , Estudos Prospectivos , Pirrolidinas , Quinoxalinas , RNA Viral/sangue , Terapia de Salvação , Sofosbuvir/administração & dosagem , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Resultado do Tratamento , Valina/análogos & derivados , Carga Viral , Proteínas não Estruturais Virais/antagonistas & inibidores , Viremia/complicações , Viremia/patologia
11.
Nephrol Dial Transplant ; 34(6): 1063-1070, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29746671

RESUMO

BACKGROUND: Recently, a risk index for living donor kidney (LDK) transplantation [living kidney donor profile index (LKDPI)] was proposed to compare LDKs with each other and with deceased donor kidneys (DDKs). Until now, the LKDPI has not been validated externally. METHODS: This long-term retrospective analysis included 1305 consecutive adult kidney transplant recipients who were transplanted 2000-16 in our centre. The Kidney Donor Profile Index (KDPI) was calculated in 889 DDKs and the LKDPI in 416 LDKs. Outcome was followed over a median of 6.5 years. RESULTS: The median LKDPI was 17 and the median KDPI was 69, with a high proportion of donor kidneys with a very high KDPI (40% KDPI ≥ 80). Categorization of LDK into LKDPI quartiles (LKDPI -45-3, 3-17, 17-33, 33-90) revealed a significant difference in death-censored graft survival. Comparing corresponding subgroups of the LKDPI and KDPI (LKDPI/KDPI 0-20 or 20-40) showed comparable graft survival. A multivariate analysis adjusting for relevant recipient factors revealed the KDPI [hazard ratio (HR) 1.21; P < 0.001) and LKDPI (HR 1.15; P = 0.049) as significant independent predictors of graft loss. Time-to-event receiver operating characteristic analyses for graft survival demonstrated lower predictive discrimination of the LKDPI [area under the curve (AUC) 0.55] compared with the KDPI (AUC 0.66). The 10-year graft survival of LDK recipients was inferior in the USA compared with our centre (79% versus 84%). CONCLUSIONS: These results provide external validation of the LKDPI to predict death-censored graft survival and confirm comparability of the LKDPI with the KDPI to discriminate post-transplant outcome.


Assuntos
Falência Renal Crônica/mortalidade , Falência Renal Crônica/cirurgia , Transplante de Rim/mortalidade , Doadores Vivos , Obtenção de Tecidos e Órgãos/métodos , Adulto , Idoso , Área Sob a Curva , Europa (Continente)/epidemiologia , Reações Falso-Positivas , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Rim , Transplante de Rim/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Medição de Risco , Estados Unidos
12.
Clin Transplant ; 32(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29052906

RESUMO

This study assessed adherence to prolonged-release tacrolimus (PR-T)-based immunosuppression during routine maintenance of renal transplant recipients in Germany. Patients had received PR-T for ≥1 month at inclusion. Data were collected during four visits (V): baseline (V1), 6 (V2), 12 (V3), and 18 (V4) months. Composite primary endpoint: nonadherence at V4, defined as self-reported nonadherence on the Basel Assessment of Adherence with Immunosuppressive Medication Scale (BAASIS© ), investigator-rated nonadherence, and/or V4 tacrolimus trough level outside a predefined range. Secondary endpoints: individual BAASIS items, incidence of rejection, kidney function, and safety. Overall, 153 adult kidney recipients (mean [standard deviation] time post-transplant 5.8 [4.6] years) were included. Nonadherence was high at V4 (67.7% [95% confidence interval 58.9%, 75.6%]). Medication-taking adherence was 86.9% and 91.3% at V1 and V4, respectively; adherence to timing of medication intake was 58.2% and 58.3%, with little evidence of missed doses/drug holidays. Investigators rated adherence "good" in 85.6% of patients (V4). Two (1.3%) patients had acute rejection episodes. Kidney function remained stable (mean creatinine clearance, V1: 62.1 mL/min; V4: 65.3 mL/min). Investigators rated effectiveness of PR-T as "very good"/"good" in 91.5% of patients. Most patients (94.7%) found PR-T dosing more convenient than immediate-release tacrolimus. PR-T was well tolerated with high medication persistence.


Assuntos
Preparações de Ação Retardada , Rejeição de Enxerto/prevenção & controle , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Adesão à Medicação/estatística & dados numéricos , Complicações Pós-Operatórias , Tacrolimo/administração & dosagem , Esquema de Medicação , Feminino , Seguimentos , Alemanha , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Imunossupressores/administração & dosagem , Testes de Função Renal , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Transplantados
13.
Transplantation ; 101(11): 2780-2788, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28658202

RESUMO

BACKGROUND: Scrupulous comparison of the pharmacokinetic and clinical characteristics of generic tacrolimus formulations versus the reference drug (Prograf) is essential. The pharmacokinetics of the Tacrolimus Hexal (TacHexal) formulation is similar to Prograf in stable renal transplant patients, but data in de novo patients are lacking. METHODS: De novo kidney transplant patients were randomized to generic tacrolimus (TacHexal) or Prograf in a 6-month open-label study. RESULTS: The primary end point, the dose-normalized area under the curve0-12h at month 1 posttransplant, was similar with TacHexal or Prograf; back-transformed geometric means of adjusted log-transformed values (analysis of variance) were 18.99 ng·h·L (TacHexal) and 20.48 ng·h·L (Prograf) (ratio, 1.08; 90% confidence interval, 0.84-1.38; P = 0.605). The dose-normalized peak concentration geometric means at month 1 was also comparable between treatments (ratio, 1.16; 90% confidence interval, 0.88-1.54; P = 0.377). There were no relevant differences in other pharmacokinetic parameters at month 1 or in area under the curve0-4h and trough concentration when measured at months 3 and 6. The adjusted change in mean estimated glomerular filtration rate from baseline to month 6 (Nankivell) was noninferior for TacHexal versus Prograf using observed values (47.7 vs 38.6 mL/min per 1.73 m, P < 0.001) and was superior based on observed values (P = 0.044) but not using last observation-carried forward method. Rates of biopsy-proven acute rejection (5.7% vs 7.9%), adverse events, and serious adverse events were similar with TacHexal or Prograf. CONCLUSION: Tacrolimus pharmacokinetics is similar with TacHexal and Prograf early after kidney transplantation. Efficacy and safety in this limited data set were comparable, with at least equivalent graft function under TacHexal.


Assuntos
Inibidores de Calcineurina/farmacocinética , Medicamentos Genéricos/farmacocinética , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/farmacocinética , Transplante de Rim , Tacrolimo/farmacocinética , Adulto , Área Sob a Curva , Biópsia , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/sangue , Monitoramento de Medicamentos , Medicamentos Genéricos/administração & dosagem , Medicamentos Genéricos/efeitos adversos , Feminino , Alemanha , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/sangue , Rim/efeitos dos fármacos , Rim/fisiopatologia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Tacrolimo/sangue , Equivalência Terapêutica , Resultado do Tratamento
14.
Artigo em Inglês | MEDLINE | ID: mdl-25520848

RESUMO

UNLABELLED: Neuroendocrine tumours (NETs) represent a broad spectrum of tumours, of which the serotonin-producing carcinoid is the most common and has been shown to cause right ventricular heart failure. However, an association between heart failure and NETs other than carcinoid has not been established so far. In this case report, we describe a 51-year-old patient with a glucagon-producing NET of the pancreas who developed acute heart failure and even cardiogenic shock despite therapy. Heart failure eventually regressed after initialising i.v. treatment with the somatostatin analogue octreotide. Chromogranin A as a tumour marker was shown to be significantly elevated, and it decreased with clinical improvement of the patient. The effects of long-time stimulation of glucagon on the myocardium have not been studied yet; however, sarcoplasmic reticulum calcium leak can be discussed as a possible mechanism for glucagon-induced heart failure. LEARNING POINTS: Glucagonoma can be a cause for heart failure.i.v. infusion of octreotide can be successfully used to treat glucagonoma-induced acute heart failure.We suggest that cardiac function should be monitored in all NET patients.

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