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Patients with type 1 diabetes and concurrent subcutaneous insulin resistance present unique diagnostic and therapeutic challenges for clinicians. The standard therapeutic approach is the administration of intravenous insulin. Pancreatic transplantation should be considered at an appropriate time, particularly in the event of life-threatening ketoacidosis, hyperglycemia, hypoglycemia, catheter-associated thrombosis and infections. We present the case of a 24-year-old female patient with type 1 diabetes since early childhood and increasingly uncontrollable subcutaneous and intramuscular insulin resistance. Furthermore, we present the diagnostic pathway and therapeutic interventions performed, culminating in pancreatic transplantation as a curative approach. Immediate graft function resulted in optimal glycemic control.
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OBJECTIVE: This study was designed to demonstrate the predictive ability of quantitative indocyanine green (ICG) fluorescence angiography for the short-term postoperative outcome, the occurrence of delayed graft function (DGF), and long-term graft survival. SUMMARY BACKGROUND DATA: DGF is a relevant problem after kidney transplantation; sufficient microperfusion of the allograft is crucial for postoperative organ function. Fluorescence angiography with ICG can serve as an intraoperative quality control of microperfusion. METHODS: This prospective diagnostic study, conducted in 2 German transplantation centers from November 2015 to October 2018, included 128 consecutive kidney transplantations. Intraoperative assessment of the allograft microperfusion was performed by near-infrared fluorescence angiography with ICG; a software was used for quantitative analysis. The associations between perfusion parameters (eg, ICG Ingress) and donor, recipient, peri-procedural, and postoperative characteristics were evaluated. RESULTS: DGF occurred in 23 (24%) kidney recipients from deceased donors. ICG Ingress ( P = 0.0027), donor age ( P = 0.0452), recipient age ( P = 0.0139), and recipient body mass index ( P = 0.0017) were associated with DGF. ICG Ingress correlated significantly with recipient age (r = -0.27662, P = 0.0016), cold and warm ischemia time (r = -0.25204, P = 0.0082; r = -0.19778, P = 0.0283), operating time (r = -0.32208, P = 0.0002), eGFR on postoperative days 1 (r =+0.22674, P = 0.0104) and 7 (r = +0.33189, P = 0.0001). The cutoff value for ICG Ingress was 106.23 AU with sensitivity of 78.3% and specificity of 80.8% ( P < 0.0001) for the prediction of DGF. CONCLUSION: Fluorescence angiography with ICG allows intraoperative quantitative assessment of microperfusion during kidney transplantation. The parameter ICG Ingress reflects recipient and procedure characteristics and is able to predict the incidence of DGF. TRIAL REGISTRATION: Clinicaltrials.gov: NCT-02775838.
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Transplante de Rim , Função Retardada do Enxerto , Angiofluoresceinografia , Sobrevivência de Enxerto , Humanos , Verde de Indocianina , Transplante de Rim/métodos , Lasers , Estudos Prospectivos , Fatores de Risco , Doadores de TecidosRESUMO
INTRODUCTION: The results of kidney transplants have improved dramatically in recent years, leading to reduced morbidity and mortality. Despite continuous improvements, urological complications occur at a rate of 2.6%-15%. Ureteral stenosis of graft ureters is the most common complication, with a probability of 0.5%-6.3%. This study aimed to determine the incidence of ureteral stenosis after kidney transplantation and identify risk factors that distinguish transplant patients with and without ureteral stenosis. METHODS: This study retrospectively analyzed patients who had undergone kidney transplantation at the Department of Urology of the Friedrich-Alexander University Erlangen-Nuremberg between 2001 and 2015. Forty-seven patients developed ureteral stenosis during the operation. Most of the ureteral stenosis cases occurred in the first 4 months after transplantation. Kaplan-Meier analysis and the log-rank test were used to calculate the cumulative risk, and the Mann-Whitney U test was used nonparametrically. The significance level was set at p < 0.05. RESULTS: Statistical analysis showed that residual diuresis (p = 0.008), cold ischemia time (CIT) (p = 0.040), the body mass index (p = 0.027), and donor serum creatinine value (p = 0.039) showed a significantly different distribution between recipients with or without ureteral stenosis after kidney transplantation. In multivariate Cox's regression modeling, residual diuresis and the donor serum creatinine level were identified as the only independent predictors of patients' stenosis-free survival. CONCLUSION: Urological complications not diagnosed and treated in time endanger the success of kidney transplantation. After evaluating the kidney transplantation data of the patients at the Transplant Center Erlangen-Nuremberg from 2001 to 2015, residual diuresis, CIT, the body mass index, and donor serum creatinine value were found to influence the development of ureteral stenosis.
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Transplante de Rim , Obstrução Ureteral , Constrição Patológica/etiologia , Creatinina , Análise Fatorial , Feminino , Humanos , Transplante de Rim/efeitos adversos , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Obstrução Ureteral/etiologiaRESUMO
OBJECTIVES: This retrospective study evaluates intraoral surgical and conservative treatment need in patients with a chronic kidney end-stage disease, depending on the duration of dialysis treatment and the causative nephrological disease. MATERIAL AND METHODS: This study is based on data of patients referred to the Department of Oral and Maxillofacial Surgery of the University Hospital Erlangen, Germany, prior to kidney transplantation between January 2015 and March 2020. The necessity for oral surgical or dental therapy was determined by clinical and radiological examinations. Data on renal replacement therapy, cause of underlying renal disease, lifestyle, and general health were collected. RESULTS: Data of N = 89 patients demonstrated that surgical treatment need depends on dialysis duration (p = 0.042). Patients, who had been dialyzing for 2 to 3 years showed the highest need for surgical intervention (80.0%; p = 0.024), followed by dialysis patients with a dialysis time of more than 3 years (48.1%). Similarly, dialysis patients in the second or third year of dialysis had the highest need for conservative treatment (73.3%; p > 0.05), followed by 55.6% of dialysis patients in the third year of dialysis. CONCLUSIONS: Operative and conservative treatment is essential to optimize subsequent kidney transplantation. The greatest necessity could be detected for patients in the second and third years of dialysis. CLINICAL RELEVANCE: Oral health addressing surgical and conservative treatment need depends on the duration of dialysis in patients with a chronic kidney end-stage disease.
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Falência Renal Crônica , Transplante de Rim , Saúde Bucal , Procedimentos Cirúrgicos Bucais , Tratamento Conservador , Alemanha , Humanos , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Diálise Renal , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Obesity is frequently present in patients suffering from end-stage renal disease (ESRD). However, overweight kidney transplant candidates are a challenge for the transplant surgeon. Obese patients tend to develop a large abdominal panniculus after weight loss creating an area predisposed to wound-healing disorders. Due to concerns about graft survival and postoperative complications after kidney transplantation, obese patients are often refused in this selective patient cohort. The study aimed to analyze the effect of panniculectomies on postoperative complications and transplant candidacy in an interdisciplinary setting. METHODS: A retrospective database review of 10 cases of abdominal panniculectomies performed in patients with ESRD prior to kidney transplantation was conducted. RESULTS: The median body mass index was 35.2 kg/m2 (range 28.5-53.0 kg/m2) at first transplant-assessment versus 31.0 kg/m2 (range 28.0-34.4 kg/m2) at panniculectomy, and 31.6 kg/m2 (range 30.3-32.4 kg/m2) at kidney transplantation. We observed no major postoperative complications following panniculectomy and minor wound-healing complications in 2 patients. All aside from 1 patient became active transplant candidates 6 weeks after panniculectomy. No posttransplant wound complications occurred in the transplanted patients. CONCLUSION: Abdominal panniculectomy is feasible in patients suffering ESRD with no major postoperative complications, thus converting previously ineligible patients into kidney transplant candidates. An interdisciplinary approach is advisable in this selective patient cohort.
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Abdominoplastia , Falência Renal Crônica/cirurgia , Transplante de Rim , Obesidade/cirurgia , Abdominoplastia/efeitos adversos , Adulto , Idoso , Bases de Dados Factuais , Feminino , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/diagnóstico , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , CicatrizaçãoRESUMO
BACKGROUND: The oral health of organ transplanted patients before organ re-transplantation is largely unknown. This retrospective clinical study evaluates the necessity for intraoral surgical intervention and/or conservative treatment in candidates awaiting organ re-transplantation, both for graft failure and for reasons of another upcoming solid organ transplantation (renal or non-renal). METHODS: From January 2015 to March 2020 n = 19 transplant recipients in evaluation on the waiting list for solid organ re-transplantation could be included in the retrospective case series study. Using clinical and radiological examinations, necessity for oral surgical or conservative dental treatment was evaluated. On the basis of anamnesis data, current kidney function, renal replacement treatment (RRT), and medication, a risk profile for several patient subgroups was created. RESULTS: The clinical and radiological examinations showed a conservative and/or surgical treatment need in n = 13 cases (68.42%). In n = 7 cases (36.84%) surgical intervention was recommended due to residual root remnants (n = 5), unclear mucosal changes (n = 1), and periimplantitis (n = 1). In n = 16 recipients (84.2%) RRT (n = 15 hemodialysis; n = 1 peritoneal dialysis) had been performed. N = 14 recipients (73.68%) received immunosuppressants. In n = 1 patient (5.3%) displayed intraoral and n = 4 patients (21.1%) extraoral neoplasms due to drug-induced immunosuppression. CONCLUSIONS: Solid organ transplant recipients with renal failure present a complex treatment profile due to a double burden of uremia plus immunosuppressants. In cases of surgical treatment need a hospitalized setting is recommended, where potentially necessary follow-up care and close cooperation with disciplines of internal medicine is possible in order to avoid surgical and/or internal complications.
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Falência Renal Crônica , Transplante de Rim , Transplante de Órgãos , Preparações Farmacêuticas , Humanos , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Saúde Bucal , Estudos RetrospectivosRESUMO
In Eurotransplant kidney allocation system (ETKAS), candidates can be considered unlimitedly for repeated re-transplantation. Data on outcome and benefit are indeterminate. We performed a retrospective 15-year patient and graft outcome data analysis from 1464 recipients of a third or fourth or higher sequential deceased donor renal transplantation (DDRT) from 42 transplant centers. Repeated re-DDRT recipients were younger (mean 43.0 vs. 50.2 years) compared to first DDRT recipients. They received grafts with more favorable HLA matches (89.0% vs. 84.5%) but thereby no statistically significant improvement of patient and graft outcome was found as comparatively demonstrated in 1st DDRT. In the multivariate modeling accounting for confounding factors, mortality and graft loss after 3rd and ≥4th DDRT (P < 0.001 each) and death with functioning graft (DwFG) after 3rd DDRT (P = 0.001) were higher as compared to 1st DDRT. The incidence of primary nonfunction (PNF) was also significantly higher in re-DDRT (12.7%) than in 1st DDRT (7.1%; P < 0.001). Facing organ shortage, increasing waiting time, and considerable mortality on dialysis, we question the current policy of repeated re-DDRT. The data from this survey propose better HLA matching in first DDRT and second DDRT and careful selection of candidates, especially for ≥4th DDRT.
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Transplante de Rim , Obtenção de Tecidos e Órgãos , Sobrevivência de Enxerto , Humanos , Rim , Estudos Retrospectivos , Doadores de Tecidos , Resultado do TratamentoRESUMO
Transplant centers now accept living donors with well-controlled hypertension. Little is known whether hypertension in living donors affects recipient's kidney function. We aimed to examine potential differences in kidneys from hypertensive donors compared to normotensive donors with respect to renal function over 36 months and histologic findings at transplantation (T0) and 12 months after transplantation (T1). Retrospective single-center analysis of 174 living donor-recipient pairs (age > 18; transplantation date 1/2008-3/2016). Hypertension in donors was defined as being on antihypertensive medication. All biopsies were assessed by the same blinded, experienced renal pathologist. Biopsies were scored for glomerulosclerosis, IFTA, and arteriosclerosis. Regression models were used to examine the relationship of donor hypertension with renal function and histologic changes. Hypertensive donors were significantly older than normotensive donors. Chronic changes such as tubular atrophy and atherosclerosis were more evident in kidneys from hypertensive donors at T0 as well as T1. Donor hypertension was independently associated with histologic changes at T0 and T1 but not with renal function over the follow period. Despite more pronounced histologic changes in kidneys from hypertensive living donors, these grafts exhibited a similar functional outcome. However, they subsequently might be at a greater risk and warrant thorough follow-up care.
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Sobrevivência de Enxerto , Hipertensão/complicações , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Rim/fisiopatologia , Doadores Vivos/provisão & distribuição , Obtenção de Tecidos e Órgãos/normas , Adulto , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
PURPOSE: The purpose of this study was to evaluate the in-use physicochemical and biological stability of the Sandoz rituximab biosimilar, marketed under the trade names Rixathon® and Riximyo® in the European Union, upon preparation for intravenous infusion. METHODS: Three batches of Rixathon®/Riximyo® in the final month of their 36 month shelf life were exposed to room temperature and light for 14 days to recapitulate a major temperature excursion. Samples were diluted to the lowest allowable concentration of 1 mg/mL in 0.9% NaCl solution in either polypropylene or polyethylene infusion bags and stored for 14 or 30 days at 5 ± 3â followed by an additional 24 h at room temperature to simulate product handling. Samples stored in infusion bags were analyzed using SEC, CEX, non-reducing CE-SDS, peptide mapping and CDC to assess physicochemical and biological stability. RESULTS: Analysis of Rixathon®/Riximyo® diluted to the lowest allowable concentration in 0.9% sodium chloride in either polypropylene or polyethylene infusion bags revealed no change in molecular weight variants, charge variants, deamidation, oxidation, overall composition or potency over a 31-day period. CONCLUSION: Physicochemical and biological analyses demonstrate that Rixathon®/Riximyo® stability is not impacted by dilution and formulation conditions required for intravenous infusion, even under worst case conditions with regard to product shelf life, temperature excursion, light exposure, dilution factor and infusion bag storage time over a 31-day period.
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Medicamentos Biossimilares/química , Rituximab/química , Embalagem de Medicamentos , Estabilidade de Medicamentos , Infusões Intravenosas , Polipropilenos , TemperaturaRESUMO
BACKGROUND: Conversion from calcineurin inhibitor (CNI) therapy to a mammalian target of rapamycin (mTOR) inhibitor following kidney transplantation may help to preserve graft function. Data are sparse, however, concerning the impact of conversion on posttransplant diabetes mellitus (PTDM) or the progression of pre-existing diabetes. METHODS: PTDM and other diabetes-related parameters were assessed post hoc in two large open-label multicenter trials. Kidney transplant recipients were randomized (i) at month 4.5 to switch to everolimus or remain on a standard cyclosporine (CsA)-based regimen (ZEUS, n = 300), or (ii) at month 3 to switch to everolimus, remain on standard CNI therapy or convert to everolimus with reduced-exposure CsA (HERAKLES, n = 497). RESULTS: There were no significant differences in the incidence of PTDM between treatment groups (log rank p = 0.97 [ZEUS], p = 0.90 [HERAKLES]). The mean change in random blood glucose from randomization to month 12 was also similar between treatment groups in both trials for patients with or without PTDM, and with or without pre-existing diabetes. The change in eGFR from randomization to month 12 showed a benefit for everolimus versus comparator groups in all subpopulations, but only reached significance in larger subgroups (no PTDM or no pre-existing diabetes). CONCLUSIONS: Within the restrictions of this post hoc analysis, including non-standardized diagnostic criteria and limited glycemia laboratory parameters, these data do not indicate any difference in the incidence or severity of PTDM with early conversion from a CsA-based regimen to everolimus, or in the progression of pre-existing diabetes. TRIAL REGISTRATION: clinicaltrials.gov , NCT00154310 (registered September 2005) and NCT00514514 (registered August 2007); EudraCT ( 2006-007021-32 and 2004-004346-40 ).
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Ciclosporina/administração & dosagem , Diabetes Mellitus/epidemiologia , Everolimo/administração & dosagem , Transplante de Rim/tendências , Estudos Multicêntricos como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Idoso , Ciclosporina/efeitos adversos , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/diagnóstico , Progressão da Doença , Everolimo/efeitos adversos , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , MasculinoRESUMO
BACKGROUND: Conversion from calcineurin inhibitor (CNI) therapy to everolimus within 6 months after kidney transplantation improves long-term graft function but can increase the risk of mild biopsy-proven acute cellular rejection (BPAR). We performed a post-hoc analysis of histological data from a randomized trial in order to further analyze histologic information obtained from indication and protocol biopsies up to 5 years after transplantation. METHODS: Biopsy samples obtained up to 5 years post-transplant were analyzed from the randomized ZEUS study, in which kidney transplant patients were randomized at month 4.5 to switch to everolimus (n = 154) or remain on cyclosporine (CsA)-based immunosuppression (n = 146). All patients received mycophenolate and steroids. RESULTS: At least one investigator-initiated biopsy was undertaken in 53 patients in each group between randomization and year 5, with a mean (SD) of 2.6 (1.7) and 2.2 (1.4) biopsies per patient in the everolimus and CsA groups, respectively. In the everolimus and CsA groups, investigator-initiated biopsies showed (i) BPAR in 12.3 and 7.5% (p = 0.182) of patients, respectively, with episodes graded mild in 22/24 and 18/20 cases (ii) CsA toxicity lesions in 4.5 and 10.3% of patients (p = 0.076) (iii) antibody-mediated rejection in 0.6 and 2.7% of patients (p = 0.204), respectively. CONCLUSIONS: This analysis of histological findings in the ZEUS study to 5 years after kidney transplantation shows no increase in antibody-mediated rejection under everolimus-based therapy with a lower rate of CNI-related toxicity compared to a conventional CsA-based regimen, and confirms the preponderance of mild BPAR seen in the main study after the early switch to CsA-free everolimus therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00154310 . Date of registration: September 12, 2005.
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Ciclosporina/administração & dosagem , Substituição de Medicamentos/tendências , Everolimo/administração & dosagem , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/administração & dosagem , Transplante de Rim/tendências , Adolescente , Adulto , Idoso , Substituição de Medicamentos/métodos , Feminino , Sobrevivência de Enxerto/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto JovemRESUMO
Living organ donation becomes more and more important as the number of patients needing organ transplantation is increasing. The University Hospital of Erlangen initiated a survey of living kidney donors to improve the process of living donation. The survey aimed to assess the donor's needs and experiences during the process of living kidney donation. From 2003 to 2014 n=199 living kidney donations were registered at the University Hospital of Erlangen. A total of n=144 living kidney donors (65.3% females, mean age M=58.7 years) participated in the study. In general, the majority of the living kidney donors were satisfied with the process of donation. Almost all of them (98%) confirmed to donate again, if it was possible. A large part of the living kidney donors denied any negative physical or psychological consequences of the donation. However, around 25% reported still physical problems for example wound healing, pain or long-term hypertension. Furthermore, a lack of pre- and post-operative psychological care or a regular medical follow-up care was reported. Thus, clinical practice needs to be further developed to meet the patient's needs.
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Transplante de Rim/psicologia , Doadores Vivos/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
Graft-versus-host disease (GVHD) remains one of the major complications after allogeneic hematopoietic stem cell transplantation that is mainly treated with glucocorticoids such as prednisolone. In this study the influence of monocyte subpopulations, prednisolone, and 1α,25-dihydroxyvitamin D3 (1α,25-(OH)2D3) on the induction of a proinflammatory subset of Th17 cells (MDR+Th17.1) characterized by CCR6+CXCR3hiCCR4loCCR10-CD161+ and stable expression of the multidrug resistance protein type 1 (MDR1) was investigated. Our results demonstrate that intermediate monocytes are increased in patients with acute GVHD, promoting the induction of proinflammatory MDR1+Th17.1 cells. Furthermore, prednisolone induces the development of MDR1+Th17.1 cells, whereas 1α,25-(OH)2D3 acts as an anti-inflammatory, leading to diminished percentages of proinflammatory MDR1+Th17.1 cells in the presence of prednisolone after stimulation with the TLR4-ligand S100A8/S100A9. Moreover, 1α,25-(OH)2D3 decreased the expression level of the targets JAK2 and CD74, both associated with T cell activation, in monocytes. Thus, in steroid-resistant GVHD, 1α,25-(OH)2D3 could be an important regulator in monocyte-induced development of proinflammatory MDR1+Th17.1 cells and might therefore be a potential therapeutic agent in combination with glucocorticoids for GVHD treatment.
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Doença Enxerto-Hospedeiro/patologia , Monócitos/citologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/análise , Adolescente , Anti-Inflamatórios/uso terapêutico , Proliferação de Células , Criança , Feminino , Humanos , Ativação Linfocitária , Masculino , Prednisolona/farmacologia , Células Th17/citologia , Vitamina D/análogos & derivados , Vitamina D/farmacologiaRESUMO
The Legionella pneumophila protein AnkX that is injected into infected cells by a Type IV secretion system transfers a phosphocholine group from CDP-choline to a serine in the Rab1 and Rab35 GTPase Switch II regions. We show here that the consequences of phosphocholination on the interaction of Rab1/Rab35 with various partner proteins are quite distinct. Activation of phosphocholinated Rabs by GTP/GDP exchange factors (GEFs) and binding to the GDP dissociation inhibitor (GDI) are strongly inhibited, whereas deactivation by GTPase activating proteins (GAPs) and interactions with Rab-effector proteins (such as LidA and MICAL-3) are only slightly inhibited. We show that the Legionella protein lpg0696 has the ability to remove the phosphocholine group from Rab1. We present a model in which the action of AnkX occurs as an alternative to GTP/GDP exchange, stabilizing phosphocholinated Rabs in membranes in the GDP form because of loss of GDI binding ability, preventing interactions with cellular GTPase effectors, which require the GTP-bound form. Generation of the GTP form of phosphocholinated Rab proteins cannot occur due to loss of interaction with cellular GEFs.
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Proteínas de Bactérias/metabolismo , Legionella pneumophila/metabolismo , Fosforilcolina/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismoRESUMO
AIMS: To assess 5-year efficacy, renal, and safety outcomes following early conversion from cyclosporine to everolimus vs. a standard cyclosporine-based regimen in living-donor kidney transplant (LDKT) recipients. MATERIALS AND METHODS: The ZEUS study was a randomized, open-label, 1-year, multicenter study in which 300 de novo kidney transplant recipients continued to receive cyclosporine or converted to everolimus at 4.5 months post-transplant, with annual follow-up visits to 5 years post-transplant. RESULTS: Of the 80 LDKT patients who were randomized, 75 completed the 1-year core study and 60 attended the 5-year follow-up visit. At year 5, 15/31 (48.4%) everolimus patients and 20/29 (69.0%) cyclosporine patients remained on the study drug. Mean adjusted estimated glomerular filtration rate (GFR) at year 5 in LDKT recipients was 67.2 vs. 60.8 mL/min/1.73m2 for everolimus vs. cyclosporine (mean difference 6.4 mL/min/1.73m2; p = 0.031). For patients who remained on study drug, the mean difference was 13.2 mL/min/1.73m2 (p = 0.003), but no significant difference was seen in patients who switched from study drug (mean -2.6 mL/min/1.73m2, p = 0.701). Patient and graft survival rates were similar with everolimus and cyclosporine. Biopsy-proven acute rejection occurred in 22.0% vs. 7.5% of LDKT patients randomized to everolimus vs. cyclosporine (p = 0.116). Only 1 LDKT patient discontinued everolimus due to adverse events during years 1 - 5. CONCLUSIONS: Early initiation of everolimus with calcineurin-inhibitor (CNI) withdrawal after LDKT improved graft function to 5 years post-transplant compared to standard CNI-based therapy. The renal benefit was concentrated in patients who remained on everolimus. An increase in mild acute rejection was not associated with long-term graft loss.
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Ciclosporina/uso terapêutico , Everolimo/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim/métodos , Doadores Vivos , Adulto , Inibidores de Calcineurina/uso terapêutico , Estudos de Coortes , Feminino , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Rejeição de Enxerto/diagnóstico , Sobrevivência de Enxerto , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Proteinúria/urina , Segurança , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The aim of this retrospective study was to report results of a consecutive series of kidney transplant patients in whom the renal artery was implanted on a prosthetic vascular graft (PVG). METHODS: Between January 2011 and December 2014, 208 deceased donor renal transplantations (68 female, 140 male, mean age 52, SD 16 years) were performed. Medical charts and outpatient clinical records of patients who had undergone renal artery implantation on a PVG were reviewed. Extensive literature research added to our 4 patients further 170 published cases during 1989 and 2015 and was compared with regular transplanted patients. Data on patient characteristics, prior vascular procedures, postoperative and long-term outcome were collected. RESULTS: Patients with transplant renal artery anastomosis on a PVG were 4 years older than the control group. Function of the graft was similar in these patients compared to regular renal transplant patients. Resistance indices assessed in our clinic over the entire follow-up period showed also no significant difference between the 2 groups. Thirty-day mortality was 6% (none in our group), which occurred mostly in combination when renal transplantation and PVG replacement was performed simultaneously. CONCLUSION: Grafting of the renal artery to a PVG is feasible and yields good results, despite the technical difficulties involved.
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Implante de Prótese Vascular/instrumentação , Prótese Vascular , Artéria Ilíaca/cirurgia , Transplante de Rim/métodos , Artéria Renal/cirurgia , Adulto , Idoso , Implante de Prótese Vascular/efeitos adversos , Angiografia por Tomografia Computadorizada , Estudos de Viabilidade , Feminino , Humanos , Artéria Ilíaca/diagnóstico por imagem , Transplante de Rim/efeitos adversos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Artéria Renal/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Ultrassonografia Doppler DuplaRESUMO
We present a new protein labeling method based on the covalent enzymatic phosphocholination of a specific octapeptide amino acid sequence in intact proteins. The bacterial enzyme AnkX from Legionella pneumophila has been established to transfer functional phosphocholine moieties from synthetically produced CDP-choline derivatives to N-termini, C-termini, and internal loop regions in proteins of interest. Furthermore, the covalent modification can be hydrolytically removed by the action of the Legionella enzyme Lem3. Only a short peptide sequence (eight amino acids) is required for efficient protein labeling and a small linker group (PEG-phosphocholine) is introduced to attach the conjugated cargo.
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Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Hidrolases/química , Hidrolases/metabolismo , Legionella pneumophila/enzimologia , Fosforilcolina/química , Repetição de Anquirina , Domínio Catalítico , Modelos Moleculares , Processamento de Proteína Pós-TraducionalRESUMO
BACKGROUND: With increased waiting times for kidney transplantation, marginal organs from expanded criteria donors (ECD) are increasingly offered for allocation. In addition to ECD status, donors may have suffered from acute kidney injury (AKI) prior to organ procurement. METHODS: In this retrospective cohort study, we studied short-term allograft function in 517 kidney transplants performed between the years 2008-2014. Recipients of allografts from deceased organ donors were categorized as standard criteria donors (SCD) or ECD with or without AKI defined by RIFLE criteria. RESULTS: Of 382 deceased donations, 174 (45.5%) were classified as ECD and 63 (16.5%) fulfilled AKI criteria. Donor creatinine on hospital admission was similar, whereas creatinine before organ procurement differed (p < 0.001). Despite these differences, serum creatinine and eGFR at discharge and after one yr showed only minor differences between kidneys with or without AKI. In multivariate linear regression analyses, donor AKI was not a predictor of one-yr allograft function. CONCLUSIONS: Given the poor prognosis of dialysis patients and the increase in waiting time, kidneys from SCD and ECD donors with AKI should be allocated for transplantation. In case of ECD donors with AKI, recipients should be informed about the possibility of permanent non-function or early graft loss.
Assuntos
Injúria Renal Aguda/complicações , Rejeição de Enxerto/fisiopatologia , Sobrevivência de Enxerto/fisiologia , Transplante de Rim , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Injúria Renal Aguda/fisiopatologia , Adulto , Aloenxertos , Cadáver , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
The German Sirolimus Study Group has established a database among 10 transplant centers throughout Germany to study the outcomes in 726 renal transplant patients being converted to a sirolimus-containing therapy between 2000 and 2008 with a total of more than 1500 recorded patient years on therapy. In this study, we present a detailed description of the cohort, of characteristic changes over the observation period, proteinuria and graft survival, and new-onset proteinuria after conversion. Over the study period, age, graft function at the time of conversion, and the proportion of patients switched to sirolimus because of malignancy increased, whereas the proportion of patients with significant proteinuria at conversion decreased. Already modest proteinuria (151-268 mg/L) at conversion and new-onset proteinuria (>500 mg/L) after conversion were associated with inferior graft survival. Even mild proteinuria (>71 mg/L) at conversion was associated with new-onset proteinuria (>500 mg/L) post-conversion. Serum creatinine and urinary protein excretion at conversion together with age at transplantation had a significant impact on patient and graft survival. This large data set confirms and extends previous observations that proteinuria is an important indicator for graft outcome after conversion to sirolimus. We conclude that patients without any proteinuria have the greatest benefit from conversion to sirolimus.
Assuntos
Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim , Complicações Pós-Operatórias , Proteinúria/diagnóstico , Sirolimo/uso terapêutico , Adulto , Creatinina/sangue , Bases de Dados Factuais , Feminino , Seguimentos , Alemanha , Rejeição de Enxerto/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Conversion of living-donor kidney transplant patients from calcineurin inhibitor therapy to an mTOR inhibitor is poorly documented. In the prospective, multicentre ZEUS study, 300 kidney transplant recipients without prior rejection (Banff grade >1) and serum creatinine ≤265 µmol/l were randomized to continue cyclosporine or convert to everolimus at 4.5 months post-transplant. In a post hoc analysis of 80 living-donor recipients, adjusted estimated GFR (Nankivell) at month 12 (the primary endpoint) was 74.3 (95% CI [70.7, 77.9]) ml/min/1.73 m(2) with everolimus versus 63.8 (95% CI [60.0, 67.7]) ml/min/1.73 m(2) ) with cyclosporine, a difference of 10.5 ml/min/1.73 m(2) in favour of everolimus (P < 0.001). From randomization to month 12, adjusted estimated GFR increased by a mean of 9.8 (95% CI [6.2, 13.4]) ml/min/1.73 m(2) with everolimus versus -0.7 (95% CI [-4.6, 3.1]) ml/min/1.73 m(2) ) (P < 0.001) with cyclosporine. There were six biopsy-proven acute rejection episodes in everolimus-treated patients (five Banff grade I) and one episode in cyclosporine-treated patients (Banff grade 1). Overall safety profile was similar between groups. Discontinuation due to adverse events occurred in three everolimus patients (7.1%) and five cyclosporine patients (13.2%) between randomization and month 12. Initiation of everolimus with early elimination of calcineurin therapy is associated with a significant renal benefit at 12 months post-transplant that is observed in both living and deceased-donor recipients. (clinicaltrials.gov NCT00154310).