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1.
Pediatr Transplant ; 27(5): e14542, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37194409

RESUMO

BACKGROUND: Kidneys from infants with anuric acute kidney injury (AKI) only rarely get accepted for transplantation despite encouraging data that such kidneys can have very good long-term outcome. METHODS: We report the transplantation of four kidney grafts from two pediatric donors (3 and 4 years) with anuric acute kidney injury as single kidneys into four adult recipients. RESULTS: All grafts gained function within 14 days posttransplantation, only one recipient needed dialysis after transplantation. None of the recipients suffered from surgical complications. One month after transplantation, all recipients were free of dialysis. Estimated glomerular filtration rates (eGFR) 3 months after transplantation were 37, 40, 50, and 83 mL/min/1.73 m2 . eGFR increased further through month 6, reaching 45, 50, 58, and 89 mL/min/1.73 m2 . CONCLUSION: These cases highlight the feasibility of successful transplantation of single pediatric kidney grafts into adult recipients despite anuric AKI of the donor.


Assuntos
Injúria Renal Aguda , Anuria , Transplante de Rim , Lactente , Humanos , Criança , Adulto , Rim , Doadores de Tecidos , Injúria Renal Aguda/cirurgia , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Estudos Retrospectivos
2.
Am J Transplant ; 21(8): 2833-2845, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33725408

RESUMO

Personalizing immunosuppression is a major objective in transplantation. Transplant recipients are heterogeneous regarding their immunological memory and primary alloimmune susceptibility. This biomarker-guided trial investigated whether in low immunological-risk kidney transplants without pretransplant DSA and donor-specific T cells assessed by a standardized IFN-γ ELISPOT, low immunosuppression (LI) with tacrolimus monotherapy would be non-inferior regarding 6-month BPAR than tacrolimus-based standard of care (SOC). Due to low recruitment rates, the trial was terminated when 167 patients were enrolled. ELISPOT negatives (E-) were randomized to LI (n = 48) or SOC (n = 53), E+ received the same SOC. Six- and 12-month BPAR rates were higher among LI than SOC/E- (4/35 [13%] vs. 1/43 [2%], p = .15 and 12/48 [25%] vs. 6/53 [11.3%], p = .073, respectively). E+ patients showed similarly high BPAR rates than LI at 6 and 12 months (12/55 [22%] and 13/66 [20%], respectively). These differences were stronger in per-protocol analyses. Post-hoc analysis revealed that poor class-II eplet matching, especially DQ, discriminated E- patients, notably E-/LI, developing BPAR (4/28 [14%] low risk vs. 8/20 [40%] high risk, p = .043). Eplet mismatch also predicted anti-class-I (p = .05) and anti-DQ (p < .001) de novo DSA. Adverse events were similar, but E-/LI developed fewer viral infections, particularly polyoma-virus-associated nephropathy (p = .021). Preformed T cell alloreactivity and HLA eplet mismatch assessment may refine current baseline immune-risk stratification and guide immunosuppression decision-making in kidney transplantation.


Assuntos
Transplante de Rim , Tacrolimo , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Teste de Histocompatibilidade , Humanos , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Linfócitos T , Tacrolimo/uso terapêutico
3.
Haematologica ; 106(2): 363-374, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31879324

RESUMO

Recurrence of cytomegalovirus reactivation remains a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Monitoring cytomegalovirus-specific cellular immunity using a standardized assay might improve the risk stratification of patients. A prospective multicenter study was conducted in 175 intermediate- and high-risk allogeneic hematopoietic stem cell transplant recipients under preemptive antiviral therapy. Cytomegalovirus-specific cellular immunity was measured using a standardized IFN-γ ELISpot assay (T-Track® CMV). Primary aim was to evaluate the suitability of measuring cytomegalovirus-specific immunity after end of treatment for a first cytomegalovirus reactivation to predict recurrent reactivation. 40/101 (39.6%) patients with a first cytomegalovirus reactivation experienced recurrent reactivations, mainly in the high-risk group (cytomegalovirus-seronegative donor/cytomegalovirus-seropositive recipient). The positive predictive value of T-Track® CMV (patients with a negative test after the first reactivation experienced at least one recurrent reactivation) was 84.2% in high-risk patients. Kaplan-Meier analysis revealed a higher probability of recurrent cytomegalovirus reactivation in high-risk patients with a negative test after the first reactivation (hazard ratio 2.73; p=0.007). Interestingly, a post-hoc analysis considering T-Track® CMV measurements at day 100 post-transplantation, a time point highly relevant for outpatient care, showed a positive predictive value of 90.0% in high-risk patients. Our results indicate that standardized cytomegalovirus-specific cellular immunity monitoring may allow improved risk stratification and management of recurrent cytomegalovirus reactivation after hematopoietic stem cell transplantation. This study was registered at www.clinicaltrials.gov as #NCT02156479.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Citomegalovirus , Infecções por Citomegalovirus/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Prospectivos , Medição de Risco , Ativação Viral
4.
Gesundheitswesen ; 83(S 01): S33-S38, 2021 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-34731891

RESUMO

The German living donor register Safety of the Living Kidney Donor - The German National Register (SOLKID-GNR) collects data of the medical and psychosocial outcome of living kidney donors. For the first time in Germany, a prospective data collection allows a scientifically based long-term analysis of how a living kidney donation influences the psychological and physical health of living kidney donors. This will contribute directly to improve the information and care of living kidney donors.


Assuntos
Transplante de Rim , Doadores Vivos , Coleta de Dados , Alemanha/epidemiologia , Serviços de Saúde , Humanos
5.
Zentralbl Chir ; 146(6): 586-596, 2021 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-34872114

RESUMO

BACKGROUND: Education of medical students in surgery not only consists of knowledge about diseases and their treatment but also of practical skills like i.e. suturing. In the clinical training of medical students, professional interaction and communication with patients is a key component. Due to the circumstances of distancing and reduced exposure to patients during the COVID-19 pandemic, clinical training of medical students has been challenging. To combat these restrictions, digital modern teaching concepts had to be implemented. MATERIAL AND METHODS: Surgical education of medical students was reorganised during the summer semester 2020 and winter semester 2020/2021 and the necessary adjustments, as well as their evaluation by students, were analysed. Results were compared to the pre-COVID evaluations of the summer semester 2019. Furthermore a survey of all university surgical departments in Germany (n = 39) was conducted to compare the different approaches to handling this very new situation. RESULTS: All participating centres were performing surgical education with medical students during the COVID-19 pandemic. Overall, digital teaching methods were well accepted by students and teachers, even though short-term changes were necessary during the second wave of the pandemic. Both students and teachers missed the direct mutual interaction as well as with patients (summer semester 2020 36%, winter semester 2020/2021 40%). Modern and digital teaching concepts were assessed positively (summer semester 2020 45%, winter semester 2020/2021 40%) and long term implementation was desired by students and teachers (winter semester 2020/2021 60%). CONCLUSION: Training of practical surgical skills, as well as communication skills, can only be taught in presence. Digital learning concepts can support, but not replace, surgical courses held in presence, including contact to patients and manual training. Blended learning concepts facilitate a leap towards modern teaching concepts and increase the quality of classes spent in presence.


Assuntos
COVID-19 , Estudantes de Medicina , Currículo , Humanos , Pandemias , SARS-CoV-2
6.
Eur J Immunol ; 49(5): 758-769, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30785638

RESUMO

The pathogenesis of primary sclerosing cholangitis (PSC), an autoimmune liver disease, remains unknown. The aim of this study was to characterize peripheral blood and intrahepatic NK cells from patients with PSC. Peripheral blood samples from patients with PSC, other autoimmune liver diseases, and from healthy control individuals were used, as well as liver tissues from PSC patients undergoing liver transplantation. Multiparameter flow cytometry showed that peripheral blood NK cells from PSC patients were significantly enriched for CCR7+ and CXCR3+ cells, and CCR7+ but not CXCR3+ cells were also significantly increased within intrahepatic NK cells. PSC patients undergoing liver transplantation furthermore had significantly higher plasma levels of the CCR7-ligand CCL21, and the CXCR3-ligands CXCL10 and CXCL11, and significantly higher levels of CCL21, but not CXCL10, were detected in liver tissues. CCR7+ and CXCR3+ NK cells from PSC patients exhibited significantly higher functional capacity in peripheral blood, but not liver tissues, consistent with chronic activation of these NK cells in the inflamed liver. These data show that PSC is characterized by intrahepatic CCL21 expression and accumulation of CCR7+ NK cells in the inflamed liver tissue.


Assuntos
Quimiocina CCL21/genética , Colangite Esclerosante/etiologia , Colangite Esclerosante/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Receptores CCR7/metabolismo , Biomarcadores , Quimiocina CCL21/metabolismo , Colangite Esclerosante/patologia , Suscetibilidade a Doenças , Expressão Gênica , Humanos , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Contagem de Linfócitos , Especificidade de Órgãos/genética , Receptores CXCR3/metabolismo
7.
Am J Transplant ; 19(2): 475-487, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29900661

RESUMO

Tolerance induction through simultaneous hematopoietic stem cell and renal transplantation has shown promising results, but it is hampered by the toxicity of preconditioning therapies and graft-versus-host disease (GVHD). Moreover, renal function has never been compared to conventionally transplanted patients, thus, whether donor-specific tolerance results in improved outcomes remains unanswered. We collected follow-up data of published cases of renal transplantations after hematopoietic stem cell transplantation from the same donor and compared patient and transplant kidney survival as well as function with caliper-matched living-donor renal transplantations from the Austrian dialysis and transplant registry. Overall, 22 tolerant and 20 control patients were included (median observation period 10 years [range 11 months to 26 years]). In the tolerant group, no renal allograft loss was reported, whereas 3 were lost in the control group. Median creatinine levels were 85 µmol/l (interquartile range [IQR] 72-99) in the tolerant cohort and 118 µmol/l (IQR 99-143) in the control group. Mixed linear-model showed around 29% lower average creatinine levels throughout follow-up in the tolerant group (P < .01). Our data clearly show stable renal graft function without long-term immunosuppression for many years, suggesting permanent donor-specific tolerance. Thus sequential transplantation might be an alternative approach for future studies targeting tolerance induction in renal allograft recipients.


Assuntos
Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas/mortalidade , Falência Renal Crônica/mortalidade , Transplante de Rim/mortalidade , Doadores Vivos/provisão & distribuição , Adolescente , Adulto , Aloenxertos , Estudos de Casos e Controles , Terapia Combinada , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo , Adulto Jovem
8.
Clin Transplant ; 32(7): e13288, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29779255

RESUMO

INTRODUCTION: When a sufficiently high-quality liver is available, classic liver graft splitting is performed. In such cases, a small child receives the left-lateral split graft, with subsequent transplantation of the right-extended graft in an adult. METHODS: We analyzed 64 patients who received right-extended liver grafts from 2007 to 2015, and compared outcomes between cases of external vs in-house graft splitting. RESULTS: We found excellent donor data and comparable recipient characteristics. Cold ischemic time was significantly longer for external (14 ± 2 hours; n = 38) vs internal (12 ± 2 hours; n = 26) liver graft splitting. Compared to the internal splitting group, the external liver graft splitting group showed significantly reduced 1- and 5-year patient survival (100% vs 84%; P = .035) and higher rates of biliary (24% vs 12%) and vascular (8% vs 0%) complications. CONCLUSIONS: The outcomes following right-extended split LTX are disappointing given the excellent organ quality. External liver graft splitting was associated with worse outcome and surgical complication rates. This may be related to the prolonged cold ischemic time due to twofold transportation, as well as the ignorance of the splitting procedure details and related pitfalls.


Assuntos
Sobrevivência de Enxerto , Transplante de Fígado/mortalidade , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos , Adulto , Cadáver , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
9.
Transpl Int ; 31(4): 436-450, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29284181

RESUMO

Impaired cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) is a major cause of CMV reactivation and associated complications in solid-organ transplantation. Reliably assessing CMV-CMI is desirable to individually adjust antiviral and immunosuppressive therapy. This study aimed to evaluate the suitability of T-Track® CMV, a novel IFN-γ ELISpot assay based on the stimulation of peripheral blood mononuclear cells with pp65 and IE-I CMV proteins, to monitor CMV-CMI following kidney transplantation. A prospective longitudinal multicenter study was conducted in 86 intermediate-risk renal transplant recipients. CMV-CMI, CMV viral load, and clinical complications were monitored over 6 months post-transplantation. Ninety-five percent and 88-92% ELISpot assays were positive pre- and post-transplantation, respectively. CMV-specific response was reduced following immunosuppressive treatment and increased in patients with graft rejection, indicating the ability of the ELISpot assay to monitor patients' immunosuppressive state. Interestingly, median pp65-specific response was ninefold higher in patients with self-clearing viral load compared to antivirally treated patients prior to first viral load detection (P < 0.001), suggesting that reactivity to pp65 represents a potential immunocompetence marker. Altogether, T-Track® CMV is a highly sensitive IFN-γ ELISpot assay, suitable for the immunomonitoring of CMV-seropositive renal transplant recipients, and with a potential use for the risk assessment of CMV-related clinical complications (ClinicalTrials.gov Identifier: NCT02083042).


Assuntos
Infecções por Citomegalovirus/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Imunidade Celular , Fosfoproteínas/imunologia , Complicações Pós-Operatórias/diagnóstico , Proteínas da Matriz Viral/imunologia , Adulto , Idoso , Citomegalovirus/imunologia , Infecções por Citomegalovirus/imunologia , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/virologia , Humanos , Imunossupressores , Transplante de Rim , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas , Complicações Pós-Operatórias/imunologia , Estudos Prospectivos , Adulto Jovem
10.
Pediatr Transplant ; 22(2)2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29341388

RESUMO

This is the first report of using piggyback technique for the venous anastomosis in two pediatric recipients of small en bloc kidneys, which was found to be effective to avoid twisting of the grafts and vessels. The donors were aged 2 and 3 years with a body weight of 17 and 20 kg. The recipient age was 14 and 16 years with a body weight of 42 and 54 kg. The implantation was done extraperitoneally in the right iliac fossa. The donor's inferior vena cava was anastomosed to the recipient's distal caval vein side-to-side using 6-0 polydioxanone running suture as the piggyback technique, initially dealing with the short vena cava graft in the first case. At the end of the operation, the kidneys were positioned allowing the lateral aspect of each renal unit to face anteriorly as "closing the book." The cold ischemia time was 895 and 820 minutes, respectively. No vascular complication was observed postoperatively. The patients were discharged on POD 16 and POD 21 with an eGFR of 94 and 102 mL/min/1.73 m², respectively. The graft function is stable during the 5- and 7-month follow-up.


Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Adolescente , Pré-Escolar , Humanos
11.
PLoS Med ; 14(4): e1002286, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28441386

RESUMO

BACKGROUND: Graft-derived cell-free DNA (GcfDNA), which is released into the blood stream by necrotic and apoptotic cells, is a promising noninvasive organ integrity biomarker. In liver transplantation (LTx), neither conventional liver function tests (LTFs) nor immunosuppressive drug monitoring are very effective for rejection monitoring. We therefore hypothesized that the quantitative measurement of donor-derived cell-free DNA (cfDNA) would have independent value for the assessment of graft integrity, including damage from acute rejection. METHODS AND FINDINGS: Traditional LFTs were performed and plasma GcfDNA was monitored in 115 adults post-LTx at three German transplant centers as part of a prospective, observational, multicenter cohort trial. GcfDNA percentage (graft cfDNA/total cfDNA) was measured using droplet digital PCR (ddPCR), based on a limited number of predefined single nucleotide polymorphisms, enabling same-day turn-around. The same method was used to quantify blood microchimerism. GcfDNA was increased >50% on day 1 post-LTx, presumably from ischemia/reperfusion damage, but rapidly declined in patients without graft injury within 7 to 10 d to a median <10%, where it remained for the 1-y observation period. Of 115 patients, 107 provided samples that met preestablished criteria. In 31 samples taken from 17 patients during biopsy-proven acute rejection episodes, the percentage of GcfDNA was elevated substantially (median 29.6%, 95% CI 23.6%-41.0%) compared with that in 282 samples from 88 patients during stable periods (median 3.3%, 95% CI 2.9%-3.7%; p < 0.001). Only slightly higher values (median 5.9%, 95% CI 4.4%-10.3%) were found in 68 samples from 17 hepatitis C virus (HCV)-positive, rejection-free patients. LFTs had low overall correlations (r = 0.28-0.62) with GcfDNA and showed greater overlap between patient subgroups, especially between acute rejection and HCV+ patients. Multivariable logistic regression modeling demonstrated that GcfDNA provided additional LFT-independent information on graft integrity. Diagnostic sensitivity and specificity were 90.3% (95% CI 74.2%-98.0%) and 92.9% (95% CI 89.3%-95.6%), respectively, for GcfDNA at a threshold value of 10%. The area under the receiver operator characteristic curve was higher for GcfDNA (97.1%, 95% CI 93.4%-100%) than for same-day conventional LFTs (AST: 95.7%; ALT: 95.2%; γ-GT: 94.5%; bilirubin: 82.6%). An evaluation of microchimerism revealed that the maximum donor DNA in circulating white blood cells was only 0.068%. GcfDNA percentage can be influenced by major changes in host cfDNA (e.g., due to leukopenia or leukocytosis). One limitation of our study is that exact time-matched GcfDNA and LFT samples were not available for all patient visits. CONCLUSIONS: In this study, determination of GcfDNA in plasma by ddPCR allowed for earlier and more sensitive discrimination of acute rejection in LTx patients as compared with conventional LFTs. Potential blood microchimerism was quantitatively low and had no significant influence on GcfDNA value. Further research, which should ideally include protocol biopsies, will be needed to establish the practical value of GcfDNA measurements in the management of LTx patients.


Assuntos
DNA/sangue , Rejeição de Enxerto/sangue , Transplante de Fígado , Adulto , Idoso , Área Sob a Curva , Biomarcadores/sangue , Quimerismo , Feminino , Alemanha , Rejeição de Enxerto/diagnóstico , Hepacivirus , Humanos , Leucócitos/metabolismo , Testes de Função Hepática , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC
12.
Clin Lab ; 63(9): 1393-1401, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28879711

RESUMO

BACKGROUND: Although the determination of the ABO antibody titers is necessary for the decision-making in ABOincompatible (ABOi) kidney transplantations, various methods for the determination of the ABO antibody titers are being used. However, the absence of uniform standards makes their comparability far more difficult. Two of the most commonly used methods are the tube method and the gel card method. In this study, we systematically investigate to what extent these two methods affect the result of ABO antibody titers. METHODS: ABO antibodies were determined from plasmas of 90 donors (30 individuals each with blood group A, B, and O). Seven further donors with blood group A, B, and AB provided erythrocytes for the testing. A total of 360 ABO antibody titers were determined; 180 tests for each method, each with 90 determinations of immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody titers. In addition, we also made a differentiation by blood groups to find out if and to what extent the blood groups have an impact on the results. RESULTS: Our analysis shows that the choice of method has a highly significant (p < 0.0001) impact on the titer level of the ABO antibodies. The median values of ABO antibody titers determined by using the gel card method are two titer steps lower than the titers, which are determined when using the tube method. Moreover, our data shows that there are major differences in the ABO antibody titer level among the blood groups, regardless of the choice of methods. CONCLUSIONS: We consider changing to the gel card method for determining the ABO antibody titers as a simple and effective way to achieve a standardized and uniform method. Here, too, the clinicians should be provided with sufficient information by the laboratories, in order to draw the right consequence from this change, while considering all the relevant data. As a consequence of this study, the transplant center of the University of Hamburg-Eppendorf paired a change from tube to gel card regarding the ABO antibody titer determination of ABOi kidney transplantations with an intensification of the preoperative target titer from ≤ 1:8 to ≤ 1:4.


Assuntos
Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Transplante de Rim , Sistema ABO de Grupos Sanguíneos , Eritrócitos , Humanos , Imunoensaio/métodos , Imunoglobulina G/análise , Imunoglobulina M/análise
13.
Transpl Infect Dis ; 18(6): 850-855, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27639176

RESUMO

BACKGROUND: BK polyomavirus (BKV) infection and BKV nephropathy (BKVN) are risk factors for allograft function and survival. METHODS: We retrospectively analyzed BK viremia and BKVN in 348 patients who received a kidney transplantation donated after brain death (n=232) or living donation (n=116) between 2008 and 2013. A total of 266 patients were treated with standard immunosuppression consisting of basiliximab induction, calcineurin inhibitor (CNI), and mycophenolic acid (MPA, n=219) or everolimus (n=47); 82 patients received more intense immunosuppression with lymphocyte depletion, CNI and MPA (n=38) or everolimus (n=44). RESULTS: BK viremia occurred in 33 (9.5%) patients in the first year and in 7 (2.0%) recipients in the second year after transplantation. BKVN occurred in 4 (1.1%) patients in the first year. Donor and recipient age, diabetes, previous transplantation, and type of transplantation (donated after brain death vs living donation) were not risk factors (P>.05). BK incidence did not differ depending on induction or maintenance immunosuppression. CONCLUSION: Incidence of BK viremia is independent of recipient characteristics, type of transplantation as well as induction and maintenance immunosuppression.


Assuntos
Vírus BK/efeitos dos fármacos , Terapia de Imunossupressão/efeitos adversos , Imunossupressores/uso terapêutico , Nefropatias/epidemiologia , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/epidemiologia , Infecções Tumorais por Vírus/epidemiologia , Viremia/epidemiologia , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Vírus BK/isolamento & purificação , Basiliximab , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/uso terapêutico , Everolimo/administração & dosagem , Everolimo/efeitos adversos , Everolimo/uso terapêutico , Feminino , Alemanha/epidemiologia , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Incidência , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Nefropatias/virologia , Quimioterapia de Manutenção/efeitos adversos , Quimioterapia de Manutenção/métodos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Infecções por Polyomavirus/virologia , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo/efeitos adversos , Infecções Tumorais por Vírus/virologia , Viremia/virologia
14.
Clin Transplant ; 29(11): 1029-38, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26333845

RESUMO

BACKGROUND: A fundamental goal in living kidney donation (LKD) is to maximize donor safety while minimizing post-operative impairments. We evaluated clinical outcome and health-related quality of life (QOL) comparing anterior vertical mini-incision donor nephrectomy (MIDN) and retroperitoneoscopic donor nephrectomy (RPDN). METHODS: Thirty-eight MIDN and 45 RPDN donors were analyzed. In a subsample (n = 18 MIDN; n = 32 RPDN), QOL was prospectively assessed with the WHOQOL-Bref questionnaire before and three months after LKD. RESULTS: Skin-to-skin time (169 vs. 116 min, p < 0.001) and hospital stay (6.6 vs. 4.9 d, p < 0.001) were significantly shorter in RPDN. In total, 26% of MIDN patients and 13% of RPDN patients developed post-operative complications (p = 0.14). While in MIDN the QOL domains physical health (p = 0.03) and psychological (p = 0.03) and the overall QOL facet (p = 0.003) were significantly lower three months post-LKD compared to baseline, there were no significant QOL decreases in RPDN. However, no significant post-operative QOL differences were found between groups. RPDN donors retrospectively reported significantly less post-operative pain (p = 0.007) and physical strain (p = 0.05) caused by LKD than MIDN donors. CONCLUSIONS: It may be possible to further reduce the surgical burden of LKD by introducing RPDN. Post-operative QOL was not significantly different between groups, but the QOL decrease appeared to be less pronounced in RPDN.


Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Doadores Vivos , Nefrectomia/métodos , Qualidade de Vida , Espaço Retroperitoneal/cirurgia , Coleta de Tecidos e Órgãos/métodos , Feminino , Seguimentos , Humanos , Laparoscopia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Período Pós-Operatório , Prognóstico , Estudos Prospectivos
15.
Clin Transplant ; 29(3): 252-60, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25598053

RESUMO

The population of kidney transplant (KTx) recipients often has complex medical and immunological conditions. Surgical complications (SCs) contribute to the increasing morbidity and costs in these patients. We analyzed the risk factors for SC in 405 KTx patients treated using defined immunosuppressive regimens according to their clinical and immunological risk profile: (1) standard immunosuppression (SIS) with IL-2 receptor mAb, CNI, and (a) mycophenolic acid (MPA) or (b) mTOR inhibitor; and (2) more intense immunosuppression (IIS) with (a) ATG or (b) the additional use of plasma exchange and B- and T-cell-depleting agents. In a mixed effects logistic regression model, we identified the following risk factors for SC: male gender, diabetes, and post-operative dialysis. No difference was found between the patients who received SIS with MPA and those who received mTOR inhibitors. The risk of suffering complications with IIS increases with age. In addition to IIS, diabetes was a risk for wound healing disorders. Therapeutic anticoagulation and a third or subsequent retransplantation increased the rate of bleeding. We did not identify immunosuppression or patient demographics as risk factors for lymphoceles or ureter complications; however, we demonstrated that the surgeon had a significant impact on severe complications, especially those of the ureter.


Assuntos
Transplante de Rim , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Feminino , Seguimentos , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
16.
Clin Transplant ; 29(4): 359-64, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25627801

RESUMO

B cells and their regulation by B-cell activating factor BAFF are of growing interest in kidney transplantation (KTx). There is evidence that high serum (s) BAFF leads to increased allosensitization and impaired long-term graft function. We prospectively investigated sBAFF, peripheral blood lymphocytes (PBL), and donor-specific HLA antibodies (DSA) in patients after ABOi with B-cell depleting rituximab induction treatment and compared them to a group of blood group-compatible (ABOc) living donor kidney recipients. Twelve patients after ABOi and 18 after ABOc were included. After rituximab treatment prior to ABOi, B cells remained significantly lower 1 year after KTx (1.2% (0.0-17.8) compared to ABOc of 8.6% (2.8-35.0), p = 0.0004, and also BAFF-R expression was significantly lower in ABOi (p < 0.006). sBAFF remained elevated 1 year post-Tx compared to ABOc (3615 ± 1800 vs. 1394 ± 493 pg/mL, p < 0.004). Kidney function was not significantly different between both groups after 1, 2, and 3 years. The use of rituximab in ABOi together with maintenance immunosuppression leads to significant elevation of sBAFF and lowering of B-cell numbers for more than 1 year, and this does not correlate with worse 3-year graft outcome.


Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Fator Ativador de Células B/imunologia , Linfócitos B/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Falência Renal Crônica/imunologia , Transplante de Rim , Rituximab/imunologia , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Fatores Imunológicos/imunologia , Fatores Imunológicos/uso terapêutico , Falência Renal Crônica/cirurgia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Fatores de Risco , Rituximab/uso terapêutico
17.
Clin Transplant ; 29(11): 1021-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26333844

RESUMO

ABO-incompatible (ABOi) kidney transplantation (KTx) has become an accepted therapeutic option in renal replacement therapy for patients without a blood group-compatible living donor. Using different desensitization strategies, most centers apply B-cell depletion with rituximab and maintenance immunosuppression (IS) with tacrolimus and mycophenolic acid. This high load of total IS leads to an increased rate of surgical complications and virus infections in ABOi patients. Our aim was to establish ABOi KTx using an immunosuppressive regimen, which is effective in preventing acute rejection without increasing the risk for viral infections. Therefore, we selected a de novo immunosuppressive protocol with low-dose calcineurin inhibitor and the mTOR inhibitor everolimus for our ABOi program. Here, we report the first 25 patients with a complete three-yr follow-up treated with this regimen. Three-yr patient survival and graft survival were 96% and 83%. The rate of acute T-cell-mediated rejections was low (12%). Cytomegalovirus (CMV) infection was evident in one patient only (4%). Surgical complications were common (40%), but mild in 80% of cases. We demonstrate that ABOi KTx with a de novo mTOR inhibitor-based regimen is feasible without severe surgical or immunological complications and a low rate of viral infections.


Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim , Serina-Treonina Quinases TOR/antagonistas & inibidores , Everolimo/uso terapêutico , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Testes de Função Renal , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Fatores de Risco , Tacrolimo/uso terapêutico
18.
Nat Genet ; 38(11): 1242-4, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17013395

RESUMO

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability.


Assuntos
Proteínas do Citoesqueleto/genética , Genes Ligados ao Cromossomo X , Proteínas de Membrana/genética , Nistagmo Congênito/genética , Encéfalo/embriologia , Encéfalo/metabolismo , Mapeamento Cromossômico , Cromossomos Humanos X , Proteínas do Citoesqueleto/fisiologia , Movimentos Oculares/genética , Movimentos Oculares/fisiologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Ligação Genética , Humanos , Masculino , Proteínas de Membrana/fisiologia , Mutação/fisiologia , Linhagem , Retina/metabolismo
19.
Chirurgie (Heidelb) ; 95(2): 129-134, 2024 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-37973621

RESUMO

Every patient with kidney failure requiring dialysis in Germany has the right to at least be evaluated for a transplantation. When an affected person can be considered for a transplantation, it must be clarified which allocation program is the right one for the person and whether a living organ donor can be considered. It should also be individually discussed with patients which type of donor organ should be accepted. Following a transplantation an individualized immunosuppression is relevant not only for the long-term survival of the transplant but also for the adherence of the patient.


Assuntos
Falência Renal Crônica , Transplante de Rim , Humanos , Diálise Renal , Doadores Vivos , Alemanha , Falência Renal Crônica/cirurgia
20.
Chirurgie (Heidelb) ; 2024 Jun 12.
Artigo em Alemão | MEDLINE | ID: mdl-38866960

RESUMO

The interdisciplinary additional advanced training in transplantation medicine (ZWB) has been passed with the (Model) Advanced Training Regulation 2018 and is now implemented in all federal states. It includes joint interdisciplinary contents that must be mastered by all disciplines and special skills that are specific to the individual disciplines. An organ-specific training is also possible. With its interdisciplinary approach the ZWB transplantation certification is pioneering the structure of modern transplantation centers and will thus further improve the quality of treatment for patients on the waiting lists for organ transplantation and for patients with transplanted organs.

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