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1.
Pediatr Transplant ; 28(5): e14790, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38837638

RESUMO

BACKGROUND: Probiotics are living microorganisms that may confer health benefits to their host if administered in sufficient quantities. However, data on the use of probiotics in transplant recipients are scarce. METHOD: This multi-center survey of pediatric nephrologists aimed to examine variations in practice regarding the use of probiotics in pediatric kidney transplant recipients. The survey was conducted via a 10-item questionnaire (developed in Survey Monkey) administered to pediatric nephrologists participating in the Pediatric Nephrology Research Consortium meeting in April 2023. RESULTS: Sixty-four pediatric nephrologists completed the survey. Twenty-seven (42.2%) respondents reported having prescribed probiotics to pediatric kidney transplant recipients. The primary reason for probiotic use was the treatment of antibiotic-associated diarrhea (n = 20), with other reasons including recurrent Clostridium difficile infection (n = 15), general gut health promotion (n = 12), recurrent urinary tract infections (n = 8), and parental request (n = 1). Of those who prescribed probiotics, 48.1% held them during periods of neutropenia and 14.8% during central venous line use. Of the 64 respondents, 20 reported the lack of safety data as a concern for using probiotics in kidney transplant recipients. CONCLUSION: Pediatric nephrologists are increasingly prescribing probiotics to pediatric kidney transplant recipients; nevertheless, substantial practice variations exist. The paucity of safety data is a significant deterrent to probiotic use in this population.


Assuntos
Transplante de Rim , Padrões de Prática Médica , Probióticos , Humanos , Probióticos/uso terapêutico , Criança , Nefrologia/métodos , Medicina Baseada em Evidências , Masculino , Feminino , Inquéritos e Questionários , Complicações Pós-Operatórias/prevenção & controle , Transplantados , Pediatria , Adolescente
2.
Hastings Cent Rep ; 54(3): 28-34, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38842853

RESUMO

In 1971, two years before Roe v. Wade affirmed federal protection for abortion, Judith Jarvis Thomson attempted to demonstrate the wrongs of forced gestation through analogy: you awake to find that the world's most esteemed violinist is wholly, physically dependent on you for life support. Here, the authors suggest that Thomson's intuition, that there is a relevant similarity between providing living kidney support and forced gestation, is realized in the contemporary practice of living organ donation. After detailing the robust analogy between living kidney donation and gestation, we turn to current ethical guidelines incorporated in the United Network for Organ Sharing's requirements for legally authorized organ donation and transplantation. We conclude that if, as we-and Thomson-suggest, organ donation and gestation are relevantly similar, then the ethical framework supporting donation may aid in articulating ethical grounds that will be compelling in informing the legal grounds for a defense of abortion.


Assuntos
Aborto Induzido , Obtenção de Tecidos e Órgãos , Humanos , Obtenção de Tecidos e Órgãos/ética , Obtenção de Tecidos e Órgãos/legislação & jurisprudência , Aborto Induzido/ética , Aborto Induzido/legislação & jurisprudência , Feminino , Gravidez , Estados Unidos , Doadores Vivos/ética , Transplante de Rim/ética , Transplante de Órgãos/ética
4.
J Robot Surg ; 18(1): 239, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833043

RESUMO

Robot-assisted kidney transplantation (RAKT) is a relatively novel, minimally invasive option for kidney transplantation. However, clarity on recipient selection in the published literature is lacking thereby significantly limiting interpretation of safety and other outcomes. This systematic review aimed to identify and synthesize the data on selection of RAKT recipients, compare the synthesized data to kidney transplant recipients across the USA, and explore geographical clusters of availability of RAKT. Systematic literature review, in accordance with PRISMA, via OVID MEDLINE, Embase, and Web of science from inception to March 5, 2023. All data entry double blinded and quality via Newcastle Ottawa Scale. 44 full-text articles included, encompassing approximately 2402 kidney transplant recipients at baseline but with considerable suspicion for overlap across publications. There were significant omissions of information across studies on patient selection for RAKT and/or analysis. Overall, the quality of studies was very low. Given suspicion of overlap across studies, it is difficult to determine how many RAKT recipients received living (LD) versus deceased donor (DD) organs, but a rough estimate suggests 89% received LD. While the current RAKT literature provides preliminary evidence on safety, there are significant omissions in reporting on patient selection for RAKT which limits interpretation of findings. Two recommendations: (1) international consensus is needed for reporting guidelines when publishing RAKT data and (2) larger controlled trials consistently reporting recipient characteristics are needed to clearly determine selection, safety, and outcomes across both LD and DD recipients.


Assuntos
Transplante de Rim , Seleção de Pacientes , Procedimentos Cirúrgicos Robóticos , Transplante de Rim/métodos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/normas , Acessibilidade aos Serviços de Saúde
5.
BMC Nephrol ; 25(1): 187, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824513

RESUMO

BACKGROUND: This study examines medication adherence among kidney transplant patients at St. Paul's Hospital Millennium Medical College (SPHMMC) in Addis Ababa, Ethiopia, focusing on the level of adherence and associated factors to immunosuppressant medicines. METHODS AND MATERIALS: A cross-sectional study was conducted on 270 patients from October 2021 to January 2022 using a structured questionnaire analyzed with SPSS version 26. The prevalence of medication adherence was computed, and a binary logistic regression was fitted to estimate the association. Medication adherence level measurement in post-kidney transplant patients was assessed using the Simplified Medication Adherence Questionnaire (SMAQ) and Basel Adherence Assessment Scale in Immunosuppressants (BAASIS). A 95% confidence interval and p-value < 0.05 were used for statistical significance. RESULTS: The study found that 71.5% of kidney transplant patients were male, with a median age of 37 and a mean duration of 3.55 years. Medication adherence in post-kidney transplant patients was 81.9%. Post-transplant duration above 5 years and missing follow-up visits more than two times was associated with a 92.6% and 91.2% in medication non-adherence rate respectively. Additionally, forgetfulness was associated with a 90.6%, non-adherence level compared to drug unavailability and financial reasons. CONCLUSION AND RECOMMENDATION: The study indicates that our patients exhibit higher medication adherence than WHO-measured levels, suggesting the need for healthcare providers to strengthen their intervention, especially for those above 5 years post-kidney transplant. The reason for increased adherence could be explained by the health education program about the medication name, dosing, frequency of ingestion and adverse effects of the drug, and effects of non-adherence.


Assuntos
Hospitais de Ensino , Imunossupressores , Transplante de Rim , Adesão à Medicação , Humanos , Masculino , Etiópia/epidemiologia , Feminino , Adulto , Estudos Transversais , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Adulto Jovem , Inquéritos e Questionários
6.
BMC Med Educ ; 24(1): 652, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862944

RESUMO

BACKGROUND: Patient involvement is crucial to the success of kidney transplants. This study aimed to investigate the knowledge, attitude, and practice (KAP) toward postoperative self-management among kidney transplant recipients. METHODS: A web-based cross-sectional study was conducted in Ruijin Hospital (Shanghai, China) between March 24, 2023, and April 15, 2023 in kidney transplant recipients. A questionnaire was designed to collect data about the characteristics of the participants and their KAP toward postoperative self-management. KAP scores were calculated based on participants' responses, using predefined scoring criteria tailored to evaluate each dimension of KAP effectively. RESULTS: A total of 483 valid questionnaires were collected, including 189 (39.13%) participants aged between 46 and 60 years. The mean score of knowledge, attitude and practice were 23.44 ± 4.87 (possible range: 0-28), 43.59 ± 2.65 (possible range: 10-50), 52.52 ± 4.64 (possible range: 0-58), respectively. The multivariate analysis showed knowledge scores (OR = 1.15, 95% CI = 1.10-1.20, p < 0.001), attitude scores (OR = 1.22, 95% CI = 1.12-1.32, p < 0.001) and undergone transplantation within 1 year (OR = 3.92, 95% CI = 1.60-9.63, p = 0.003) were independently associated with good practice. Knowledge scores (OR = 1.06, 95% CI = 1.02-1.10, p = 0.003), attitude scores (OR = 1.16, 95% CI = 1.08-1.25, p < 0.001), aged 16-35 years (OR = 0.38, 95% CI = 0.18-0.78, p = 0.009), underwent a single kidney transplant surgery (OR = 3.97, 95% CI = 1.28-12.38, p = 0.017) were independently associated with medication adherence. CONCLUSIONS: Kidney transplant recipients had good knowledge, positive attitude and good practice toward postoperative self-management. Implementing personalized education, psychological support, and close monitoring strategies is recommended to optimize postoperative self-management in kidney transplant recipients.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Transplante de Rim , Autogestão , Humanos , Pessoa de Meia-Idade , Estudos Transversais , Masculino , Feminino , Adulto , Transplantados/psicologia , Inquéritos e Questionários , China , Cuidados Pós-Operatórios
7.
Transpl Int ; 37: 12963, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38868358

RESUMO

Cytomegalovirus (CMV) infection detrimentally influences graft survival in kidney transplant recipients, with the risk primarily determined by recipient and donor serostatus. However, recipient CD8+ T cells play a crucial role in CMV control. The optimal preventive strategy (prophylaxis vs. pre-emptive treatment), particularly for seropositive (intermediate risk) recipients, remains uncertain. We investigated CD8+ T cell subpopulation dynamics and CMV occurrence (DNAemia ≥ 100 IU/mL) in 65 kidney transplant recipients, collecting peripheral blood mononuclear cells before (T1) and 1 year after transplantation (T2). Comparing the two timepoints, we found an increase in granulocyte, monocyte and CD3+CD8+ T cells numbers, while FoxP3+CD25+, LAG-3+ and PD-1+ frequencies were reduced at T2. CMV DNAemia occurred in 33 recipients (55.8%) during the first year. Intermediate risk patients were disproportionally affected by posttransplant CMV (N = 29/45, 64.4%). Intermediate risk recipients developing CMV after transplantation exhibited lower leukocyte, monocyte, and granulocyte counts and higher FoxP3+CD25+ frequencies in CD3+CD8+ T cells pre-transplantation compared to patients staying CMV negative. Pre-transplant FoxP3+CD25+ in CD3+CD8+ T cells had the best discriminatory potential for CMV infection prediction within the first year after transplantation (AUC: 0.746). The FoxP3+CD25+ CD3+CD8+ T cell subset may aid in selecting intermediate risk kidney transplant recipients for CMV prophylaxis.


Assuntos
Linfócitos T CD8-Positivos , Infecções por Citomegalovirus , Fatores de Transcrição Forkhead , Subunidade alfa de Receptor de Interleucina-2 , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/prevenção & controle , Feminino , Masculino , Linfócitos T CD8-Positivos/imunologia , Pessoa de Meia-Idade , Fatores de Transcrição Forkhead/metabolismo , Adulto , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Idoso , Complexo CD3/metabolismo , Citomegalovirus/imunologia , Fatores de Risco , Transplantados , Sobrevivência de Enxerto/imunologia
8.
Sci Transl Med ; 16(751): eadk6152, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865482

RESUMO

Genetic modification of porcine donors, combined with optimized immunosuppression, has been shown to improve outcomes of experimental xenotransplant. However, little is known about outcomes in sensitized recipients, a population that could potentially benefit the most from the clinical implementation of xenotransplantation. Here, five highly allosensitized rhesus macaques received a porcine kidney from GGTA1 (α1,3-galactosyltransferase) knockout pigs expressing the human CD55 transgene (1KO.1TG) and were maintained on an anti-CD154 monoclonal antibody (mAb)-based immunosuppressive regimen. These recipients developed de novo xenoreactive antibodies and experienced xenograft rejection with evidence of thrombotic microangiopathy and antibody-mediated rejection (AMR). In comparison, three highly allosensitized rhesus macaques receiving a kidney from GGTA1, CMAH (cytidine monophospho-N-acetylneuraminic acid hydroxylase), and b4GNT2/b4GALNT2 (ß-1,4-N-acetyl-galactosaminyltransferase 2) knockout pigs expressing seven human transgenes including human CD46, CD55, CD47, THBD (thrombomodulin), PROCR (protein C receptor), TNFAIP3 (tumor necrosis factor-α-induced protein 3), and HMOX1 (heme oxygenase 1) (3KO.7TG) experienced significantly prolonged graft survival and reduced AMR, associated with dampened post-transplant humoral responses, early monocyte and neutrophil activation, and T cell repopulation. After withdrawal of all immunosuppression, recipients who received kidneys from 3KO.7TG pigs rejected the xenografts via AMR. These data suggest that allosensitized recipients may be suitable candidates for xenografts from genetically modified porcine donors and could benefit from an optimized immunosuppression regimen designed to target the post-transplant humoral response, thereby avoiding AMR.


Assuntos
Animais Geneticamente Modificados , Galactosiltransferases , Técnicas de Inativação de Genes , Rejeição de Enxerto , Sobrevivência de Enxerto , Transgenes , Transplante Heterólogo , Animais , Sobrevivência de Enxerto/imunologia , Humanos , Suínos , Galactosiltransferases/genética , Galactosiltransferases/deficiência , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Macaca mulatta , Transplante de Rim
9.
Wiad Lek ; 77(4): 765-771, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38865635

RESUMO

OBJECTIVE: Aim: To determine the economic feasibility of using kidney transplantation compared to hemodialysis in end-stage renal disease in the long term in countries with a low and medium level of economic development using the example of Ukraine. PATIENTS AND METHODS: Materials and Methods: The cost effectiveness analysis method was used. Conducted Markov modeling and comparison of the consequences of kidney transplantation and hemodialysis in terms of treatment costs and the number of added years of life for a cohort of 1,675 patients were carried out. The incremental cost-effectiveness ratio is defined. RESULTS: Results: Based on the results of modeling, it was determined that among 1,675 patients with end-stage kidney disease in Ukraine, 1,248 (74.5%) will remain alive after 10 years of treatment when kidney transplantation technology is used. The highest costs will be in the first year ($25,864), and in subsequent years - about $5,769. With the use of hemodialysis technology, only 728 patients (43.5%) will be alive after 10 years, the cost of treating one patient per year is $11,351. The use of kidney transplantation adds 3191 years of quality life for 1675 patients compared with hemodialysis (1.9 years per patient). CONCLUSION: Conclusions: Kidney transplantation is an economically feasible technology for Ukraine, as the incremental cost-effectiveness ratio is $4694, which is 1.04 times higher than Ukraine's GDP per capita. The results of the study allow us to recommend that decision-makers in countries with a low and medium level of economic development give priority in financing to renal transplantation.


Assuntos
Análise Custo-Benefício , Falência Renal Crônica , Transplante de Rim , Diálise Renal , Humanos , Transplante de Rim/economia , Ucrânia , Falência Renal Crônica/cirurgia , Falência Renal Crônica/economia , Falência Renal Crônica/terapia , Diálise Renal/economia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Custos de Cuidados de Saúde/estatística & dados numéricos
10.
World J Urol ; 42(1): 373, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869666

RESUMO

INTRODUCTION/OBJECTIVE: Graft stones in renal transplant recipients pose a unique challenge, finding effective interventions to ensure optimal graft function and patient well-being. Various methods of stone clearance have been described for graft stones, including percutaneous nephrolithotomy (PCNL). While PCNL is a promising approach for managing graft stones, specific outcomes and associated characteristics for this approach have not been comprehensively evaluated before. This study aims to evaluate the safety and efficacy of the use of PCNL as the primary intervention of graft stones by assessing stone-free rates (SFR), treatment impact on graft function, and perioperative complications. METHODS: A retrospective clinical audit was performed for all transplants performed in a single center from 2007 to 2022, which included all graft lithiasis patients who were treated with PCNL. Both perioperative parameters and post-operative outcomes were collected. In addition, a systematic review including articles from MEDLINE, Embase, Web of Science yielded 18 full-text articles published between 1/1/2000 and 15/11/2023. The results pertaining to patients who underwent PCNLs for graft stones were cross-referenced and thoroughly evaluated. The review encompassed a comprehensive analysis of clinical data, postoperative outcomes, and procedural details. The protocol for the systematic review was prospectively registered on PROSPERO (CRD42023486825). RESULTS: In our center, 6 graft lithiasis patients were treated with PCNL. The initial SFR was 83.3%. SFR at 3 months and 1 year were both 100.0%. SFR at 3 years was 66.7%. Other centers reported initial SFR of 82.6-100.0% (interquartile range). SFR at 3 months, 1 year, 3 years was not well reported across the included studies. Incidence of graft lithiasis ranged from 0.44%-2.41%. Most common presentations at diagnosis were oliguria/anuria/acute kidney injury and asymptomatic. Reported complications included blood loss, transient hematuria, high urine output, sepsis, and damage to surrounding structures. The most commonly reported metabolic abnormalities in transplant lithiasis patients included hyperuricemia and hyperparathyroidism. CONCLUSION: PCNL is a practical and efficient choice for addressing graft lithiasis, demonstrating excellent stone clearance and minimal perioperative complications. These findings show the importance of PCNL as a primary intervention in this complex patient population.


Assuntos
Transplante de Rim , Nefrolitotomia Percutânea , Humanos , Nefrolitotomia Percutânea/métodos , Nefrolitotomia Percutânea/efeitos adversos , Estudos Retrospectivos , Adulto , Cálculos Renais/cirurgia , Masculino , Feminino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pessoa de Meia-Idade
11.
J Med Virol ; 96(6): e29742, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38874263

RESUMO

Polyomaviruses BK (BKPyV) and JC (JCPyV), belonging to the Polyomaviridae, are responsible for human pathologies. In kidney transplant recipients, BKPyV replication can lead to irreversible nephron damage whereas JCPyV replication remains asymptomatic. Concomitant replication is rare and potential competition between the infections has been described. The aim of this retrospective case-control study was to describe the molecular epidemiology and risk factors associated with BKPyV and JCPyV replication in a cohort of kidney transplant recipients. In total, 655 urine samples from 460 patients were tested for BKPyV and JCPyV DNA. Positive samples were submitted to strain genotyping. Demographic and clinical characteristics were also compared. Isolated JCPyV and BKPyV was found in 16.5% and 23.3% of patients, respectively; co-replication was rare (3.9%). BKPyV strains Ib-2, Ib-1, and IVc-2 were the most prevalent. JCPyV strains mostly belonged to genotypes 4 and 1B. During follow-up, JCPyV shedding significantly reduced the risk of BKPyV DNAuria, with an odds ratio of 0.57 (95% confidence interval: 0.35-0.99), and was associated with better prognosis than BKPyV replication, based on the estimated glomerular filtration rate. Molecular epidemiology of BKPyV and JCPyV strains in our region was similar to previous studies. This study suggests that JCPyV is benign and appears to limit damaging BKPyV replication. JCPyV DNAuria screening could thus be a useful strategy to predict BKPyV-related outcomes.


Assuntos
Vírus BK , Genótipo , Vírus JC , Transplante de Rim , Epidemiologia Molecular , Infecções por Polyomavirus , Humanos , Vírus BK/genética , Vírus BK/isolamento & purificação , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/virologia , Infecções por Polyomavirus/urina , Transplante de Rim/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Vírus JC/genética , Vírus JC/isolamento & purificação , Estudos de Casos e Controles , Adulto , Eliminação de Partículas Virais , Idoso , Transplantados/estatística & dados numéricos , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/virologia , Infecções Tumorais por Vírus/urina , DNA Viral/urina , DNA Viral/genética , Aloenxertos/virologia
12.
Nephrol Ther ; 20(3): 1-10, 2024 06 14.
Artigo em Francês | MEDLINE | ID: mdl-38874420

RESUMO

The management of patients with kidney transplant failure (KTF) remains a complex process involving multiple stakeholders. A working group of the Transplantation Commission of the French-speaking Society of Nephrology, Dialysis and Transplantation (SFNDT) conducted a survey on the management of immunosuppressants (IS) after KTF among nephrologists at transplant centres and general nephrologists in France, Switzerland and Belgium between March and June 2023. We analysed 232 replies from 58 nephrologists at transplant centres and 174 general nephrologists, aged 43.6 (+10.6) years. In the first three months following KTF, nephrologists reported discontinuing antimetabolite, calcineurin inhibitor (CNI) and corticosteroid treatment in 83%, 39.9% and 25.8% of cases respectively. Conversely, some nephrologists reported that they were continuing to use CNI (14%) and corticosteroids (19.1%) on a long-term basis. The patient's comorbidities associated with the discontinuation of IS treatment are cancer and opportunistic infections as KT's complications and presence of diabetes mellitus at KTF, whereas humoral rejection encourages the IS to be maintained. Transplantectomy is proposed by nephrologists most often for graft intolerance syndrome (86.5%), more rarely to discontinue IS (17.6%) or in the absence of plans of new transplantation (9.3%). In multivariate analyses, the presence of a protocol in the centre facilitated the management of IS by the general nephrologists. The management of IS after AFG by French-speaking nephrologists is heterogeneous. Specific prospective studies are needed to establish new best practice recommendations, based on more robust evidence, which could encourage better adherence by nephrologists.


La prise en charge des patients avec un arrêt fonctionnel du greffon rénal (AFG) reste un processus complexe avec de multiples intervenants. Un groupe de travail de la Société francophone de néphrologie, dialyse et transplantation (SFNDT) a conduit une enquête sur la gestion des traitements immunosuppresseurs (IS) après AFG parmi les néphrologues de centres de transplantation et néphrologues généraux en France, Suisse et Belgique francophone entre mars et juin 2023. Nous avons pu analyser 232 réponses de néphrologues (centres de transplantation N = 58 et généraux N = 174) âgés de 43,6 (± 10,6) ans. Dans les 3 premiers mois suivant l'AFG, les néphrologues déclarent interrompre le traitement par antimétabolites (83 %), inhibiteurs de la calcineurine (ICN) (39,9 %) et corticoïdes (25,8 %). À l'inverse, certains déclarent maintenir les ICN (14 %) et les corticoïdes (19,1 %) au long cours en cas de projet de nouvelle transplantation rénale (TR). La survenue de cancer pendant la TR, d'infections opportunistes dans la dernière année de TR ou à l'initiation de la dialyse, et la présence d'un diabète lors de l'AFG sont associées avec l'arrêt du traitement IS alors que la perte du greffon par rejet humoral incite à le maintenir. En analyse multivariée, la présence d'un protocole dans le centre facilite la gestion des IS par les néphrologues généraux. Enfin, la transplantectomie est proposée par les néphrologues le plus souvent pour un syndrome d'intolérance du greffon (86,5 %), plus rarement pour interrompre les IS (17,6 %) ou en l'absence de projet de nouvelle TR (9,3 %). La gestion des IS après l'AFG par les néphrologues francophones est hétérogène. Des études prospectives spécifiques sont nécessaires afin de formuler de nouvelles recommandations de bonnes pratiques, reposant sur des données probantes plus robustes, qui pourraient encourager une meilleure adhésion par les néphrologues.


Assuntos
Rejeição de Enxerto , Imunossupressores , Transplante de Rim , Nefrologistas , Padrões de Prática Médica , Humanos , Imunossupressores/uso terapêutico , França , Adulto , Rejeição de Enxerto/prevenção & controle , Masculino , Feminino , Suíça , Inquéritos e Questionários , Pessoa de Meia-Idade , Bélgica , Nefrologia
13.
Sci Rep ; 14(1): 12855, 2024 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834615

RESUMO

BK virus-associated nephropathy (BKVAN) exerts a substantial impact on allograft survival, however, the absence of robust clinical evidence regarding treatment protocols adds to the complexity of managing this condition. This study aimed to compare the two treatment approaches. The study population consisted of patients who underwent kidney transplantation between January 2016 and June 2020 at two tertiary hospitals in Korea. Patients diagnosed with BK viremia were evaluated based on their initial viral load and the treatment methods. The 'Reduction group' involved dose reduction of tacrolimus while the 'Conversion group' included tacrolimus discontinuation and conversion to sirolimus. A total of 175 patients with an initial viral load (iVL) ≥ 3 on the log10 scale were evaluated within two iVL intervals (3-4 and 4-5). In the iVL 4-5 interval, the Reduction group showed potential effectiveness in terms of viral clearance without statistically significant differences. However, within the iVL 3-4 interval, the Reduction group demonstrated superior viral clearance and a lower incidence of biopsy-proven acute rejection (BPAR) than the Conversion group. The renal function over 12 months after BKV diagnosis showed no statistically significant difference. Reducing tacrolimus compared to converting to mTORi would be a more appropriate treatment approach for BK viral clearance in kidney transplantation. Further research is warranted in a large cohort of patients.


Assuntos
Vírus BK , Inibidores de Calcineurina , Imunossupressores , Transplante de Rim , Infecções por Polyomavirus , Serina-Treonina Quinases TOR , Tacrolimo , Viremia , Humanos , Transplante de Rim/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Inibidores de Calcineurina/uso terapêutico , Viremia/tratamento farmacológico , Infecções por Polyomavirus/tratamento farmacológico , Tacrolimo/uso terapêutico , Adulto , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Imunossupressores/uso terapêutico , Carga Viral/efeitos dos fármacos , Resultado do Tratamento , Infecções Tumorais por Vírus/tratamento farmacológico , Infecções Tumorais por Vírus/virologia , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/prevenção & controle , Sirolimo/uso terapêutico , República da Coreia , Estudos Retrospectivos , Idoso
14.
Sci Rep ; 14(1): 12901, 2024 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839764

RESUMO

Early kidney injury may be detected by urinary markers, such as beta-2 microglobulin (B2M), tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), kidney injury molecule-1 (KIM-1) and/or neutrophil gelatinase-associated lipocalin (NGAL). Of these biomarkers information on pathophysiology and reference ranges in both healthy and diseased populations are scarce. Differences in urinary levels of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL were compared 24 h before and after nephrectomy in 38 living kidney donors from the REnal Protection Against Ischaemia-Reperfusion in transplantation study. Linear regression was used to assess the relation between baseline biomarker concentration and kidney function 1 year after nephrectomy. Median levels of urinary creatinine and creatinine standardized B2M, TIMP-2, IGFBP7, KIM-1, NGAL, and albumin 24 h before nephrectomy in donors were 9.4 mmol/L, 14 µg/mmol, 16 pmol/mmol, 99 pmol/mmol, 63 ng/mmol, 1390 ng/mmol and 0.7 mg/mmol, with median differences 24 h after nephrectomy of - 0.9, + 1906, - 7.1, - 38.3, - 6.9, + 2378 and + 1.2, respectively. The change of donor eGFR after 12 months per SD increment at baseline of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL was: - 1.1, - 2.3, - 0.7, - 1.6 and - 2.8, respectively. Urinary TIMP-2 and IGFBP7 excretion halved after nephrectomy, similar to urinary creatinine, suggesting these markers predominantly reflect glomerular filtration. B2M and NGAL excretion increased significantly, similar to albumin, indicating decreased proximal tubular reabsorption following nephrectomy. KIM-1 did not change considerably after nephrectomy. Even though none of these biomarkers showed a strong relation with long-term donor eGFR, these results provide valuable insight into the pathophysiology of these urinary biomarkers.


Assuntos
Biomarcadores , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Nefrectomia , Inibidor Tecidual de Metaloproteinase-2 , Microglobulina beta-2 , Humanos , Nefrectomia/métodos , Nefrectomia/efeitos adversos , Inibidor Tecidual de Metaloproteinase-2/urina , Microglobulina beta-2/urina , Masculino , Feminino , Pessoa de Meia-Idade , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Adulto , Biomarcadores/urina , Transplante de Rim/efeitos adversos , Doadores Vivos , Rim/cirurgia , Rim/fisiopatologia , Rim/metabolismo , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Receptor Celular 1 do Vírus da Hepatite A/análise , Creatinina/urina , Lipocalina-2/urina
15.
Pediatr Transplant ; 28(5): e14801, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38845603

RESUMO

BACKGROUND: Approximately 2500 pediatric patients are awaiting kidney transplantation in the United States, with <5% comprising those ≤15 kg. Transplant in this cohort is often delayed by center-based growth parameters, often necessitating transplantation after the initiation of dialysis. Furthermore, prognostication remains somewhat ambiguous. In this report, we scrutinize the Organ Procurement and Transplantation Network (OPTN) data from 2001 to 2021 to help better understand specific variables impacting graft and patient outcomes in these children. METHODS: The OPTN kidney transplant dataset from 2001 to 2021 was analyzed. Inclusion criteria included age <18 years, weight ≤15 kg, and recipient of primary living donor kidney transplantation (LDKT) or deceased donor kidney transplantation (DDKT). Patient and graft survival probabilities were calculated using the Kaplan-Meier method. The Cox proportional hazards model was used to calculate hazard ratio (HR) and identify variables significantly associated with patient and graft survival. RESULTS: Two thousand one hundred sixty-eight pediatric transplant recipients met inclusion criteria. Patient survival at 1 and 3 years was 98% and 97%, respectively. Graft survival at 1 and 3 years was 95% and 92%, respectively. Dialysis was the sole significant variable impacting both patient and graft survival. Graft survival was further impacted by transplant era, recipient gender and ethnicity, and donor type. Infants transplanted at Age 1 had better graft survival compared with older children, and nephrotic syndrome was likewise associated with a better prognosis. CONCLUSION: Pediatric kidney transplantation is highly successful. The balance between preemptive transplantation, medical optimization, and satisfactory technical parameters seems to suggest a "Goldilocks zone" for many children, favoring transplantation between 1 and 2 years of age.


Assuntos
Bases de Dados Factuais , Sobrevivência de Enxerto , Transplante de Rim , Obtenção de Tecidos e Órgãos , Humanos , Criança , Feminino , Masculino , Obtenção de Tecidos e Órgãos/métodos , Pré-Escolar , Adolescente , Prognóstico , Lactente , Estados Unidos/epidemiologia , Falência Renal Crônica/cirurgia , Peso Corporal , Estimativa de Kaplan-Meier , Resultado do Tratamento , Estudos Retrospectivos , Modelos de Riscos Proporcionais , Recém-Nascido
16.
PLoS One ; 19(6): e0301425, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38843258

RESUMO

BACKGROUND: The influence of center volume on kidney transplant outcomes is a topic of ongoing debate. In this study, we employed competing risk analyses to accurately estimate the marginal probability of graft failure in the presence of competing events, such as mortality from other causes with long-term outcomes. The incorporation of immunosuppression protocols and extended follow-up offers additional insights. Our emphasis on long-term follow-up aligns with biological considerations where competing risks play a significant role. METHODS: We examined data from 219,878 adult kidney-only transplantations across 256 U.S. transplant centers (January 2001-December 2015) sourced from the Organ Procurement and Transplantation Network registry. Centers were classified into quartiles by annual volume: low (Q1 = 28), medium (Q2 = 75), medium-high (Q3 = 121), and high (Q4 = 195). Our study investigated the relationship between center volume and 5-year outcomes, focusing on graft failure and mortality. Sub-population analyses included deceased donors, living donors, diabetic recipients, those with kidney donor profile index >85%, and re-transplants from deceased donors. RESULTS: Adjusted cause-specific hazard ratios (aCHR) for Five-Year Graft Failure and Patient Death were examined by center volume, with low-volume centers as the reference standard (aCHR: 1.0). In deceased donors, medium-high and high-volume centers showed significantly lower cause-specific hazard ratios for graft failure (medium-high aCHR = 0.892, p<0.001; high aCHR = 0.953, p = 0.149) and patient death (medium-high aCHR = 0.828, p<0.001; high aCHR = 0.898, p = 0.003). Among living donors, no significant differences were found for graft failure, while a trend towards lower cause-specific hazard ratios for patient death was observed in medium-high (aCHR = 0.895, p = 0.107) and high-volume centers (aCHR = 0.88, p = 0.061). CONCLUSION: Higher center volume is associated with significantly lower cause-specific hazard ratios for graft failure and patient death in deceased donors, while a trend towards reduced cause-specific hazard ratios for patient death is observed in living donors.


Assuntos
Transplante de Rim , Transplantados , Humanos , Transplante de Rim/mortalidade , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Transplantados/estatística & dados numéricos , Sobrevivência de Enxerto , Sistema de Registros , Resultado do Tratamento , Rejeição de Enxerto , Estados Unidos , Idoso
17.
Transpl Int ; 37: 12864, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38832357

RESUMO

Simultaneous pancreas-kidney (SPK) transplantation improves quality of life and limits progression of diabetic complications. There is reluctance to accept pancreata from donors with abnormal blood tests, due to concern of inferior outcomes. We investigated whether donor amylase and liver blood tests (markers of visceral ischaemic injury) predict pancreas graft outcome using the UK Transplant Registry (2016-2021). 857 SPK recipients were included (619 following brainstem death, 238 following circulatory death). Peak donor amylase ranged from 8 to 3300 U/L (median = 70), and this had no impact on pancreas graft survival when adjusting for multiple confounders (aHR = 0.944, 95% CI = 0.754-1.81). Peak alanine transaminases also did not influence pancreas graft survival in multivariable models (aHR = 0.967, 95% CI = 0.848-1.102). Restricted cubic splines were used to assess associations between donor blood tests and pancreas graft survival without assuming linear relationships; these confirmed neither amylase, nor transaminases, significantly impact pancreas transplant outcome. This is the largest, most statistically robust study evaluating donor blood tests and transplant outcome. Provided other factors are acceptable, pancreata from donors with mild or moderately raised amylase and transaminases can be accepted with confidence. The use of pancreas grafts from such donors is therefore a safe, immediate, and simple approach to expand the donor pool to reach increasing demands.


Assuntos
Amilases , Sobrevivência de Enxerto , Transplante de Rim , Transplante de Pâncreas , Doadores de Tecidos , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Amilases/sangue , Estudos de Coortes , Alanina Transaminase/sangue , Reino Unido , Testes Hematológicos , Sistema de Registros
18.
BMC Infect Dis ; 24(1): 559, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834974

RESUMO

BACKGROUND: Kidney transplant recipients (KTRs) are at an elevated risk of progressing to severe infections upon contracting COVID-19. We conducted a study on risk factors and multi-pathogen infections in KTRs with SARS-CoV-2 Omicron variant. METHODS: KTRs were subjected to a thorough etiological evaluation. Whenever feasible, they were also provided with bronchoscopy and bronchoalveolar lavage to enable metagenomic next-generation sequencing (mNGS), ideally within a 48-hour window post-admission. We performed a retrospective analysis for pathogens and risk factors of KTRs with the COVID-19 virus variant Omicron. RESULTS: We included thirty patients in our study, with sixteen exhibiting single infection of COVID-19 and fourteen experiencing co-infections, predominantly with Pneumocystis jirovecii. Notably, patients with severe cases demonstrated significantly elevated levels of C-reactive protein (CRP) and interleukin-6 compared to those with moderate cases (P < 0.05). Furthermore, individuals whose conditions progressed had markedly higher baseline serum creatinine levels than those without such progression (P < 0.05). The presence of heart failure, acute exacerbation of renal dysfunction, and a history of opportunistic infections were significantly associated with a higher likelihood of deterioration and hospital admission due to the SARS-CoV-2 Omicron variant, as compared to the control group (P < 0.05). In subsequent follow-up analysis, the all-cause rehospitalization rate was observed to be 21.4%, with Pneumocystis jirovecii infection accounting for half of these cases. CONCLUSION: Among KTRs, a significant coinfection rate of 47% was observed, with Pneumocystis jirovecii emerging as the predominant pathogen in these cases. The development of heart failure, acute exacerbation of chronic renal dysfunction, and a prior history of opportunistic infections have been identified as potential risk factors that may contribute to clinical deterioration in KTRs. Additionally, Pneumocystis jirovecii infection has been established as a critical factor influencing the rate of all-cause rehospitalization within this patient population.


Assuntos
COVID-19 , Coinfecção , Transplante de Rim , SARS-CoV-2 , Transplantados , Humanos , Transplante de Rim/efeitos adversos , COVID-19/epidemiologia , COVID-19/virologia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Fatores de Risco , Adulto , Coinfecção/microbiologia , Coinfecção/virologia , Coinfecção/epidemiologia , Idoso , Pneumocystis carinii/genética , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/virologia , Pneumonia por Pneumocystis/epidemiologia
19.
Front Immunol ; 15: 1384823, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38840925

RESUMO

Objective: In a cooperative study of the University Hospital Leipzig, University of Leipzig, and the Charité Berlin on kidney transplant patients, we analysed the occurrence of HLA-specific antibodies with respect to the HLA setup of the patients. We aimed at the definition of specific HLA antigens towards which the patients produced these antibodies. Methods: Patients were typed for the relevant HLA determinants using mainly the next-generation technology. Antibody screening was performed by the state-of-the-art multiplex-based technology using microspheres coupled with the respective HLA alleles of HLA class I and II determinants. Results: Patients homozygous for HLA-A*02, HLA-A*03, HLA-A*24, HLA-B*07, HLA-B*18, HLA-B*35, HLA-B*44, HLA-C*03, HLA-C*04, and HLA-C*07 in the class I group and HLA-DRB1*01, HLA-DRB1*03, HLA-DRB1*07, HLA-DRB1*15, HLA-DQA1*01, HLA-DQA1*05, HLA-DQB1*02, HLA-DQB1*03(7), HLA-DQB1*06, HLA-DPA1*01, and HLA-DPB1*04 in the class II group were found to have a significant higher antibody production compared to the heterozygous ones. In general, all HLA determinants are affected. Remarkably, HLA-A*24 homozygous patients can produce antibodies towards all HLA-A determinants, while HLA-B*18 homozygous ones make antibodies towards all HLA-B and selected HLA-A and C antigens, and are associated with an elevation of HLA-DRB1, parts of DQB1 and DPB1 alleles. Homozygosity for the HLA class II HLA-DRB1*01, and HLA-DRB1*15 seems to increase the risk for antibody responses against most of the HLA class I antigens (HLA-A, HLA-B, and HLA-C) in contrast to HLA-DQB1*03(7) where a lower risk towards few HLA-A and HLA-B alleles is found. The widely observed differential antibody response is therefore to be accounted to the patient's HLA type. Conclusion: Homozygous patients are at risk of producing HLA-specific antibodies hampering the outcome of transplantation. Including this information on the allocation procedure might reduce antibody-mediated immune reactivity and prevent graft loss in a patient at risk, increasing the life span of the transplanted organ.


Assuntos
Antígenos HLA , Homozigoto , Isoanticorpos , Transplante de Rim , Humanos , Fatores de Risco , Antígenos HLA/genética , Antígenos HLA/imunologia , Isoanticorpos/imunologia , Teste de Histocompatibilidade , Alelos , Formação de Anticorpos/genética , Formação de Anticorpos/imunologia , Masculino , Feminino
20.
Int Immunopharmacol ; 136: 112409, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38850789

RESUMO

BACKGROUND: Iguratimod (IGU) is widely used in clinical practice due to its stable anti-inflammatory effects. Our previous studies have confirmed that the proportion of Th17/Treg balance in patients taking IGU altered significantly. This study aims to explore the role of IGU in antibody-mediated rejection (ABMR) and its potential mechanisms. METHODS: We conducted bioinformatics analysis of sequencing data from the GEO database to analyze the abundance of immune cell infiltration in transplanted kidney tissues. In vivo, IGU was intervened in a mice secondary skin transplantation model and a mice kidney transplantation ABMR model, and histological morphology of the grafts were examined by pathological staining, while relevant indicators were determined through qRT-PCR, immunohistochemistry, and enzyme-linked immunosorbent assay, observed T cell differentiation by flow cytometry, and preliminarily assessed the immunosuppressive effect of IGU. In vitro, we established Th17 and Treg cell induction and stimulation differentiation culture systems and added IGU for intervention to explore its effects on their differentiation. RESULTS: Through bioinformatics analysis, we found that Th17 and Treg may play important roles in the occurrence and development of ABMR. In vivo, we found that IGU could effectively reduce the damage caused by ABMR to the grafts, alleviate the infiltration of inflammatory cells in the graft tissues, and reduce the deposition of C4d in the grafts. Moreover, it is also found that IGU regulated the differentiation of Th17 and Treg cells in the spleen and peripheral blood and reduced the expression of IL-17A in the grafts and serum. In addition, same changes were observed in the induction and differentiation culture system of Th17 and Treg cells in vitro after the addition of IGU. CONCLUSION: IGU can inhibit the progression of ABMR by regulating the differentiation of Th17 and Treg cells, providing novel insights for optimizing clinical immunosuppressive treatment regimens.


Assuntos
Cromonas , Rejeição de Enxerto , Transplante de Rim , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores , Células Th17 , Animais , Células Th17/imunologia , Linfócitos T Reguladores/imunologia , Rejeição de Enxerto/imunologia , Camundongos , Cromonas/farmacologia , Masculino , Imunossupressores/uso terapêutico , Humanos , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Células Cultivadas , Sulfonamidas
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