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1.
Turkiye Parazitol Derg ; 48(2): 111-116, 2024 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-38958436

RESUMO

Objective: In patients with end-stage kidney disease, kidney transplantation is the kidney replacement therapy option that provides the most successful survival. However, immunosuppression agents administered after kidney transplantation can increase the risk of opportunistic infections. Microsporidia are obligate intracellular pathogens that can be fatal in immunosuppressed patients. The present study aimed to determine the prevalence of microsporidia in kidney transplantation recipients and the molecular characterization of the detected species. Methods: To evaluate the prevalence of renal microsporidiosis in kidney transplant recipients, the urine samples from a total of 325 patients were analyzed by real-time and nested polymerase chain reaction for Encephalitozoon spp. and Enterocytozoon bieneusi. Results: Only one (0.4%) sample from the adult patient was positive for the Encephalitozoon species, while no positivity was found in pediatric patients. It was determined as Encephalitozoon intestinalis by ITS rRNA gene region sequence analysis. A microsporidia species obtained from humans in Türkiye has been characterized for the first time and registered in GenBank. Conclusion: Our epidemiological results show that the prevalence of renal microsporidiosis in kidney transplant recipients is very low. In addition, as a result of the phylogenetic analysis of the detected isolate, it was observed that it was 100% identical to the isolates reported from dogs in Kayseri, Türkiye. This situation provided essential data regarding the zoonotic transmission dynamics of microsporidia.


Assuntos
Encephalitozoon , Encefalitozoonose , Transplante de Rim , Microsporidiose , Filogenia , Humanos , Transplante de Rim/efeitos adversos , Prevalência , Masculino , Adulto , Encefalitozoonose/epidemiologia , Feminino , Encephalitozoon/genética , Encephalitozoon/isolamento & purificação , Criança , Turquia/epidemiologia , Microsporidiose/epidemiologia , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Reação em Cadeia da Polimerase , Hospedeiro Imunocomprometido , Pré-Escolar , Idoso , Enterocytozoon/genética , Enterocytozoon/isolamento & purificação , Animais
2.
Appl Microbiol Biotechnol ; 108(1): 402, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951204

RESUMO

Delayed graft function (DGF) is a frequently observed complication following kidney transplantation (KT). Our prior research revealed dynamic shifts in salivary microbiota post-KT with immediate graft function (IGF), yet its behavior during DGF remains unexplored. Five recipients with DGF and 35 recipients with IGF were enrolled. Saliva samples were collected during the perioperative period, and 16S rRNA gene sequencing was performed. The salivary microbiota of IGFs changed significantly and gradually stabilized with the recovery of renal function. The salivary microbiota composition of DGFs was significantly different from that of IGFs, although the trend of variation appeared to be similar to that of IGFs. Salivary microbiota that differed significantly between patients with DGF and IGF at 1 day after transplantation were able to accurately distinguish the two groups in the randomForest algorithm (accuracy = 0.8333, sensitivity = 0.7778, specificity = 1, and area under curve = 0.85), with Selenomonas playing an important role. Bacteroidales (Spearman's r = - 0.4872 and p = 0.0293) and Veillonella (Spearmen's r = - 0.5474 and p = 0.0125) were significantly associated with the serum creatinine in DGF patients. Moreover, the significant differences in overall salivary microbiota structure between DGF and IGF patients disappeared upon long-term follow-up. This is the first study to investigate the dynamic changes in salivary microbiota in DGFs. Our findings suggested that salivary microbiota was able to predict DGF in the early stages after kidney transplantation, which might help the perioperative clinical management and early-stage intervention of kidney transplant recipients. KEY POINTS: • Salivary microbiota on the first day after KT could predict DGF. • Alterations in salivary taxa after KT are related to recovery of renal function.


Assuntos
Função Retardada do Enxerto , Transplante de Rim , Microbiota , RNA Ribossômico 16S , Saliva , Humanos , Transplante de Rim/efeitos adversos , Saliva/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Adulto , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética
3.
J Immunol Res ; 2024: 6908968, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957433

RESUMO

Background: Kidney transplantation (KT) is the best treatment for end-stage renal disease. Although long and short-term survival rates for the graft have improved significantly with the development of immunosuppressants, acute rejection (AR) remains a major risk factor attacking the graft and patients. The innate immune response plays an important role in rejection. Therefore, our objective is to determine the biomarkers of congenital immunity associated with AR after KT and provide support for future research. Materials and Methods: A differential expression genes (DEGs) analysis was performed based on the dataset GSE174020 from the NCBI gene Expression Synthesis Database (GEO) and then combined with the GSE5099 M1 macrophage-related gene identified in the Molecular Signatures Database. We then identified genes in DEGs associated with M1 macrophages defined as DEM1Gs and performed gene ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. Cibersort was used to analyze the immune cell infiltration during AR. At the same time, we used the protein-protein interaction (PPI) network and Cytoscape software to determine the key genes. Dataset, GSE14328 derived from pediatric patients, GSE138043 and GSE9493 derived from adult patients, were used to verify Hub genes. Additional verification was the rat KT model, which was used to perform HE staining, immunohistochemical staining, and Western Blot. Hub genes were searched in the HPA database to confirm their expression. Finally, we construct the interaction network of transcription factor (TF)-Hub genes and miRNA-Hub genes. Results: Compared to the normal group, 366 genes were upregulated, and 423 genes were downregulated in the AR group. Then, 106 genes related to M1 macrophages were found among these genes. GO and KEGG enrichment analysis showed that these genes are mainly involved in cytokine binding, antigen binding, NK cell-mediated cytotoxicity, activation of immune receptors and immune response, and activation of the inflammatory NF-κB signaling pathway. Two Hub genes, namely CCR7 and CD48, were identified by PPI and Cytoscape analysis. They have been verified in external validation sets, originated from both pediatric patients and adult patients, and animal experiments. In the HPA database, CCR7 and CD48 are mainly expressed in T cells, B cells, macrophages, and tissues where these immune cells are distributed. In addition to immunoinfiltration, CD4+T, CD8+T, NK cells, NKT cells, and monocytes increased significantly in the AR group, which was highly consistent with the results of Hub gene screening. Finally, we predicted that 19 TFs and 32 miRNAs might interact with the Hub gene. Conclusions: Through a comprehensive bioinformatic analysis, our findings may provide predictive and therapeutic targets for AR after KT.


Assuntos
Antígeno CD48 , Rejeição de Enxerto , Transplante de Rim , Macrófagos , Mapas de Interação de Proteínas , Receptores CCR7 , Humanos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/genética , Transplante de Rim/efeitos adversos , Macrófagos/imunologia , Macrófagos/metabolismo , Animais , Criança , Ratos , Receptores CCR7/genética , Receptores CCR7/metabolismo , Antígeno CD48/genética , Antígeno CD48/metabolismo , Perfilação da Expressão Gênica , Biomarcadores , Biologia Computacional/métodos , Masculino , Redes Reguladoras de Genes , Bases de Dados Genéticas , Ontologia Genética , Modelos Animais de Doenças , Feminino , MicroRNAs/genética
4.
Exp Clin Transplant ; 22(5): 392-395, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38970283

RESUMO

We present a challenging clinical case of a 68-year-old female kidney transplant recipient who had a complicated posttransplant course marked by borderline T-cell-mediated rejection and BK virus nephropathy. The treatment for borderline rejection with steroids resulted in overimmunosuppression, and the patient acquired cytomegalovirus infection manifesting as colitis and SARS-CoV-2 infection. This progressed rapidly to collapsing glomerulopathy and allograft failure. This study also highlights the challenges in surveillance with donor-derived cell-free DNA in the setting of allograft injury by multiple viral infections.


Assuntos
Vírus BK , COVID-19 , Infecções por Citomegalovirus , Rejeição de Enxerto , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Feminino , COVID-19/complicações , COVID-19/imunologia , COVID-19/diagnóstico , Idoso , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/virologia , Infecções por Polyomavirus/diagnóstico , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/tratamento farmacológico , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/virologia , Vírus BK/patogenicidade , Vírus BK/imunologia , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologia , Infecções Tumorais por Vírus/diagnóstico , Progressão da Doença , Resultado do Tratamento , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Coinfecção
5.
Exp Clin Transplant ; 22(5): 396-398, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38970284

RESUMO

Renal transplantation is the best modality of treatment for patients with end-stage renal disease. Donor shortage remains a substantial problem, for which different strategies are employed, including acceptance of marginal donors and donor kidneys with anatomic variations. We performed a successful kidney transplant of a donor kidney that had complete duplication of the ureter. After transplant, the recipient had no urinary complications.


Assuntos
Transplante de Rim , Doadores de Tecidos , Ureter , Humanos , Transplante de Rim/efeitos adversos , Ureter/anormalidades , Ureter/cirurgia , Resultado do Tratamento , Rim/anormalidades , Rim/cirurgia , Masculino , Falência Renal Crônica/cirurgia , Falência Renal Crônica/diagnóstico , Adulto , Seleção do Doador , Feminino , Pessoa de Meia-Idade
6.
Exp Clin Transplant ; 22(5): 351-357, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38970278

RESUMO

OBJECTIVES: With the increase in life expectancy and the aging of the population, chronic kidney disease has become increasingly prevalent in our environment. Kidney transplantation remains the gold standard treatment for end-stage renal disease, but the supply of renal grafts has not been able to keep pace with growing demand. Because of this rationale, organ selection criteria have been extended (expanded criteria donation), and alternative donation types, such as donation after circulatory death, have been evaluated. These approaches aim to increase the pool of potential donors, albeit with organs of potentially lower quality. Various forms of donations, including donation after circulatory death, have also undergone assessment. This approach aims to augment the pool of potential donors, notwithstanding the compromised quality of organs associated with such methods. Diverse strategies have been explored to enhance graft function, with one of the most promising being the utilization of pulsatile machine perfusion. MATERIALS AND METHODS: We conducted a retrospective analysis on 28 transplant recipients who met the inclusion criterion of sharing the same donor, wherein one organ was preserved by cold storage and the other by pulsatile machine perfusion. We performed statistical analysis on posttransplant recovery parameters throughout the patients' hospitalization, including admission and discharge phases. RESULTS: Statistically significant differences were noted in delayed graft function (P = .04), blood transfusions requirements, and Clavien-Dindo complications. Furthermore, an overall trend of improvement in discharge parameters and hospital stay was in favor of the pulsatile machine perfusion group. CONCLUSIONS: The use of pulsatile machine perfusion as a method of renal preservation results in graft optimization, leading to earlier recovery and fewer complications compared with cold storage in the context of donation after circulatory death.


Assuntos
Função Retardada do Enxerto , Transplante de Rim , Perfusão , Fluxo Pulsátil , Recuperação de Função Fisiológica , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Fatores de Tempo , Masculino , Feminino , Perfusão/métodos , Perfusão/efeitos adversos , Pessoa de Meia-Idade , Adulto , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/prevenção & controle , Fatores de Risco , Doadores de Tecidos/provisão & distribuição , Preservação de Órgãos/métodos , Preservação de Órgãos/efeitos adversos , Seleção do Doador , Parada Cardíaca/diagnóstico , Parada Cardíaca/fisiopatologia , Parada Cardíaca/etiologia
7.
Med Sci Monit ; 30: e944285, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946121

RESUMO

BACKGROUND Thrombosis poses a grave threat to patients undergoing kidney transplants, with a heightened risk of mortality. While previous studies have established a link between COVID-19 and thrombosis, the specific association between COVID-19 and thrombosis in this patient population remains unexplored. MATERIAL AND METHODS We conducted a retrospective analysis utilizing data from 394 individuals who underwent kidney transplantation within the period of September 1, 2015, to April 1, 2023. To evaluate overall survival, we employed Kaplan-Meier analysis and utilized a logistic regression model for risk analysis. Furthermore, we developed a prediction model and assessed its accuracy through calibration curves. RESULTS Out of the 394 patients included in our study, a total of 51 individuals experienced thrombosis, resulting in 2 deaths. Our analysis revealed that COVID-19 infection significantly increased the risk of thrombosis (odds ratio [OR] 8.60, 95% confidence interval 3.13-24.74, P<0.01). Additionally, the use of cyclosporine was found to elevate the risk of death (OR 20.86, 95% CI 7.93-59.24, P<0.01) according to multifactorial analysis. Logistic models were employed to screen variables, and predictive models were constructed based on the presence of COVID-19 infection and the usage of cyclosporine. A nomogram was developed, demonstrating promising accuracy in estimating the risk of thrombosis during internal validation, with a corrected C-index of 0.869. CONCLUSIONS Our study suggests that both COVID-19 infection and the use of cyclosporine can serve as reliable predictors of thrombosis risk in patients undergoing renal transplantation. Furthermore, we developed a mortality risk prediction model based on COVID-19 in assessing thrombosis.


Assuntos
COVID-19 , Transplante de Rim , Trombose , Humanos , Transplante de Rim/efeitos adversos , COVID-19/complicações , COVID-19/epidemiologia , Trombose/etiologia , Trombose/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Incidência , Adulto , Prognóstico , Fatores de Risco , Transplantados , SARS-CoV-2 , Modelos Logísticos , Idoso , Ciclosporina/uso terapêutico , Estimativa de Kaplan-Meier
8.
Transpl Int ; 37: 12955, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38979119

RESUMO

Cigarette smoking is a common risk factor associated with negative long-term outcomes in kidney transplant recipients. However, whether donor smoking decreases graft longevity or negatively impacts recipient survival after kidney transplantation remains unknown. Therefore, this study aims to investigate the long-term outcome in patients who received a kidney graft from a deceased smoking or non-smoking donor. A total of 580 patients were divided into two groups: patients who received a graft from a smoking donor (n = 276) and those who received a graft from a non-smoking donor (n = 304). Analysis of demographic factors showed that the non-smoking cohort was older, had more extended criteria donors and longer warm ischemia times. The primary composite endpoint of patient and graft survival was better in the smoking donor cohort when analyzed using Kaplan-Meier method but not when controlled for covariates in multivariate analyses. These findings do not support a previously reported negative impact of deceased donor smoking on kidney transplant recipients. Thus, the underlying results should not be interpreted in favor of a positive donor smoking history, but rather remind the transplant community that donor smoking should not be considered as a deciding factor in refusing an otherwise acceptable kidney graft.


Assuntos
Fumar Cigarros , Sobrevivência de Enxerto , Transplante de Rim , Doadores de Tecidos , Humanos , Transplante de Rim/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Fumar Cigarros/efeitos adversos , Fatores de Risco , Resultado do Tratamento , Estimativa de Kaplan-Meier , Estudos Retrospectivos , Idoso , Fumar/efeitos adversos
9.
Transplantation ; 108(7): e139-e147, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38985979

RESUMO

BACKGROUND: Polyclonal rabbit antithymocyte globulins (ATGs) are commonly used in organ transplantation as induction. Anti- N -glycolylneuraminic acid carbohydrate antibodies which develop in response to rabbit carbohydrate antigens might lead to unwanted systemic inflammation. LIS1, the first new generation of antilymphocyte globulins (ALGs) derived from double knockout swine, lacking carbohydrate xenoantigens was already tested in nonhuman primates and rodent models. METHODS: This open-label, single-site, dose escalation, first-in-human, phase 1 study evaluated the safety, T cell depletion, pharmacokinetics, and pharmacodynamics of LIS1. In an ascending dose cohort (n = 5), a primary kidney transplant recipient at low immunologic risk (panel reactive antibody [PRA] < 20%), received LIS1 for 5 d at either 0.6, 1, 3, 6, or 8 mg/kg. After each patient completed treatment, the data safety monitoring board approved respective dose escalation. In the therapeutic dose cohort (n = 5) in patients with PRA <50% without donor specific antibodies, 2 patients received 8 mg/kg and 3 patients 10 mg/kg. RESULTS: CD3 + T cell depletion <100/mm 3 at day 2 was observed in all patients who received 6, 8, and 10 mg/kg of LIS1. The terminal half-life of LIS1 was 33.7 d with linearity in its disposition. Lymphocyte repopulation was fast and pretransplant lymphocyte subpopulation counts recovered within 2-4 wk. LIS1 was well tolerated, neither cytokine release syndrome nor severe thrombocytopenia or leukopenia were noticed. Antibodies to LIS1 were not detected. CONCLUSIONS: In this first-in-human trial, genome-edited swine-derived polyclonal LIS1 ALG was well tolerated, did not elicit antidrug antibodies, and caused time-limited T cell depletion in low- and medium-risk kidney transplant recipients.


Assuntos
Soro Antilinfocitário , Transplante de Rim , Transplante de Rim/efeitos adversos , Humanos , Animais , Soro Antilinfocitário/imunologia , Masculino , Pessoa de Meia-Idade , Suínos , Feminino , Adulto , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Depleção Linfocítica/métodos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Resultado do Tratamento , Galactosiltransferases
10.
Clin Transplant ; 38(7): e15394, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39001595

RESUMO

INTRODUCTION: Broad national or international programs contribute to mitigating the expected longer waiting list (WL) time for sensitized patients but with minor benefits for highly sensitized subjects. Therefore, strategies to prevent high sensitization are urgently required. In this study, we investigated the risk of developing highly sensitized patients with different immunosuppressive (IS) handling after kidney allograft failure (KAF). METHODS: Data from 185 patients with KAF, retransplanted/relisted from 2010 to 2020 in two regions of Italy that share the same regional WL, were analyzed. Patients were categorized according to IS management at 12 months after KAF as follows: patients maintaining IS with calcineurin inhibitors (CNI) (late withdrawal group [LWG], n = 58) and those who withdrew all IS therapy or were on steroids only (early withdrawal group [EWG], n = 127). RESULTS: Patients in the LWG showed lower panel reactive antibodies (PRA) at 12 (29.0% vs. 85.5%, p < 0.001) and 24 months (61.0% vs. 91.0%, p = 0.001), reduced risk of high sensitization (PRA ≥90%) at 12 (9.4% vs. 40.7%, p < 0.001, OR = 0.15) and 24 months (25.6% vs. 57.3%, p = 0.001, OR = 0.26) and almost no very high sensitization (PRA ≥ 98%) at 12 months (1.9% vs. 18.6%, p = 0.003, OR = 0.08) after KAF. In the LWG subgroup analysis, patients who maintained IS for up to 24 months after KAF did not show very high sensitization. The LWG showed shorter active WL times (406 vs. 813 days, p = 0.001) without an increased risk of complications. CONCLUSIONS: CNI maintenance for at least 12 months after KAF could be a useful approach to prevent high sensitization and reduce WL times in patients who are offered retransplantation, without a higher burden of complications.


Assuntos
Inibidores de Calcineurina , Rejeição de Enxerto , Sobrevivência de Enxerto , Imunossupressores , Transplante de Rim , Humanos , Masculino , Feminino , Transplante de Rim/efeitos adversos , Inibidores de Calcineurina/uso terapêutico , Pessoa de Meia-Idade , Seguimentos , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Fatores de Risco , Imunossupressores/uso terapêutico , Prognóstico , Falência Renal Crônica/cirurgia , Adulto , Taxa de Filtração Glomerular , Estudos Retrospectivos , Complicações Pós-Operatórias/prevenção & controle , Testes de Função Renal , Terapia de Imunossupressão/métodos
11.
J Med Virol ; 96(7): e29806, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39007420

RESUMO

Optimization of individual immunosuppression, which reduces the risks of both graft loss and patients' death, is considered the best approach to improve long-term outcomes of renal transplantation. Torque Teno Virus (TTV) DNAemia has emerged as a potential biomarker reflecting the depth of therapeutic immunosuppression during the initial year post-transplantation. However, its efficacy in long-term monitoring remains uncertain. In a cohort study involving 34 stable kidney transplant recipients and 124 healthy volunteers, we established lower and upper TTV DNAemia thresholds (3.75-5.1 log10 cp/mL) correlating with T-cell activatability, antibody response against flu vaccine, and risk for subsequent serious infections or cancer over 50 months. Validation in an independent cohort of 92 recipients confirmed that maintaining TTV DNAemia within this range in >50% of follow-up time points was associated with reduced risks of complications due to inadequate immunosuppression, including de novo DSA, biopsy-proven antibody-mediated rejection, graft loss, infections, or cancer. Multivariate analysis highlighted "in-target" TTV DNAemia as the sole independent variable significantly linked to decreased risk for long-term complications due to inadequate immunosuppression (odds ratio [OR]: 0.27 [0.09-0.77]; p = 0.019). Our data suggest that the longitudinal monitoring of TTV DNAemia in kidney transplant recipients could help preventing the long-term complications due to inadequate immunosuppression.


Assuntos
Infecções por Vírus de DNA , DNA Viral , Terapia de Imunossupressão , Transplante de Rim , Torque teno virus , Transplantados , Humanos , Torque teno virus/genética , Transplante de Rim/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , DNA Viral/sangue , Adulto , Infecções por Vírus de DNA/virologia , Infecções por Vírus de DNA/sangue , Infecções por Vírus de DNA/imunologia , Terapia de Imunossupressão/efeitos adversos , Estudos Longitudinais , Idoso , Rejeição de Enxerto , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Estudos de Coortes , Viremia
12.
Medicine (Baltimore) ; 103(28): e38887, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996130

RESUMO

BACKGROUND: The research aimed to assess the effectiveness of inside-out anterior quadratus lumborum (QL3) block and local wound infiltration in managing postoperative pain and total morphine dosage following kidney transplantation. METHODS: In this prospective, randomized, double-blind study; 46 end-stage renal disease patients undergoing kidney transplantation were randomly allocated into 2 groups: a QL group (n = 23) receiving 20 mL of 0.25% bupivacaine using the ultrasound-assisted inside-out technique before wound closure, while the local wound infiltration (LA) group (n = 23) receiving the same dose around the surgical wound and drain at the time of skin closure. The primary outcome measure was the numerical pain rating scale, with secondary outcomes including amount of morphine consumption at various postoperative time points (2nd, 4th, 6th, 12th, 18th and 24th hours). RESULTS: Patients in the QL group had significantly lower numerical rating scale scores at the 2nd and 4th hours, both at rest and during movement (P < .05). Although pain scores at rest and during movement at later time points were lower in the QL group compared to the LA group, these differences were not statistically significant. Cumulative morphine consumption at postoperative 4th, 6th, 12th, 18th and 24th hours was significantly lower in the QL group (P < .05). No patients experienced complications from the QL3 block. CONCLUSION: Ultrasound-assisted inside-out QL3 block significantly reduced postoperative pain levels at the 2nd and 4th hours, both at rest and during movement, and led to a reduction in cumulative morphine consumption from the 4th hour postoperatively, and persisting throughout the 24-hour period.


Assuntos
Analgésicos Opioides , Anestésicos Locais , Transplante de Rim , Morfina , Bloqueio Nervoso , Dor Pós-Operatória , Humanos , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Masculino , Método Duplo-Cego , Feminino , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Transplante de Rim/métodos , Transplante de Rim/efeitos adversos , Pessoa de Meia-Idade , Estudos Prospectivos , Bloqueio Nervoso/métodos , Morfina/administração & dosagem , Morfina/uso terapêutico , Adulto , Anestésicos Locais/administração & dosagem , Anestésicos Locais/uso terapêutico , Bupivacaína/administração & dosagem , Medição da Dor , Falência Renal Crônica/terapia , Manejo da Dor/métodos , Ultrassonografia de Intervenção/métodos
13.
Front Immunol ; 15: 1433918, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39044817

RESUMO

Introduction: The aim of this study is to investigate the clinical validity of donor-derived cell-free DNA (dd-cfDNA) in comparison with that of donor specific anti-HLA antibody (DSA) for predicting biopsy-proven rejection (BPR)and severe microvascular inflammation (severe MVI) in kidney transplant recipients (KTRs). Methods: In this prospective observational investigation, 64 KTRs who underwent the indicated biopsies were included. Blood samples collected prior to biopsy were tested for dd-cfDNA and DSA. Biopsy specimens were classified by a renal pathologist according to the Banff classification. The predictive performance of dd-cfDNA and DSA for histological allograft diagnosis was assessed. Results: KTRs were categorized into the high and low dd-cfDNA groups based on a level of 0.4%. Eighteen patients (28.1%) had positive DSA at biopsy, exhibiting higher dd-cfDNA levels than the DSA-negative patients. BPR and severe MVI incidences were elevated in the high dd-cfDNA group (BPR: 42.9% vs. 3.4%, P <0.001; severe MVI: 37.1% vs. 3.4%, P = 0.001). Also, elevated glomerulitis and MVI scores were observed in the high dd-cfDNA group. DSA showed the highest predictive value for BPR (AUC = 0.880), whereas dd-cfDNA alone excelled in predicting severe MVI (AUC = 0.855). Combination of DSA and dd-cfDNA (>0.4%) yielded sensitivities of 80.0% and 50.0% with specificities of 90.7% and 88.0% for antibody-mediated rejection and severe MVI detection, respectively. Conclusion: The dd-cfDNA test is a predictive tool for BPR and severe MVI, and it can improve the performance, especially when combined with DSA for BPR.


Assuntos
Ácidos Nucleicos Livres , Rejeição de Enxerto , Transplante de Rim , Doadores de Tecidos , Humanos , Transplante de Rim/efeitos adversos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/sangue , Ácidos Nucleicos Livres/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Prospectivos , Isoanticorpos/sangue , Isoanticorpos/imunologia , Biópsia , Biomarcadores/sangue , Antígenos HLA/imunologia , Antígenos HLA/genética , Microvasos/patologia , Microvasos/imunologia , Inflamação/imunologia , Aloenxertos/imunologia
14.
Transplantation ; 108(8): 1749-1759, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39042769

RESUMO

BACKGROUND: Xenotransplantation using pig organs is now a clinical reality. However, the process for xenograft recipient screening lacks clarity and scientific rigor: no established thresholds exist to determine which levels of preformed antipig natural antibodies (Nabs) will be safe for clinical xenograft transplantation, and hyperacute rejection (HAR) or acute humoral xenograft rejection (AHXR), which still impacts pig-to-primate kidney xenograft survivals, may impede broader application of pig-to-human clinical xenograft transplantation. METHODS: We retrospectively examined 28 cases of pig-to-baboon kidney xenotransplantation using GalTKO±human complement regulatory protein (hCRP)-transgenic (Tg) pig donors, as well as 6 cases of triple-KO multi-Tg (10GE) pig donors, and developed screening algorithms to predict risk of HAR/AHXR based on recipient antipig Nab levels. Preformed Nabs were evaluated using both complement-dependent cytotoxicity and antibody (IgM and IgG) binding flow-cytometry assays. RESULTS: High complement-dependent cytotoxicity was associated with HAR/AHXR as expected. However, we also found that high levels of IgG were independently associated with HAR/AHXR, and we developed 2 indices to interpret and predict the risk of IgG-mediated HAR/AHXR. CONCLUSIONS: Based on the data in this study, we have established a new 2-step screening, which will be used for future clinical kidney xenotransplantation trials.


Assuntos
Animais Geneticamente Modificados , Rejeição de Enxerto , Sobrevivência de Enxerto , Transplante de Rim , Transplante Heterólogo , Animais , Transplante Heterólogo/efeitos adversos , Transplante de Rim/efeitos adversos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Estudos Retrospectivos , Suínos , Fatores de Risco , Imunoglobulina G/sangue , Galactosiltransferases/genética , Galactosiltransferases/imunologia , Galactosiltransferases/deficiência , Xenoenxertos , Imunidade Humoral , Imunoglobulina M/sangue , Humanos , Masculino , Anticorpos Heterófilos/imunologia , Doença Aguda
15.
Transplantation ; 108(8): 1782-1792, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39042770

RESUMO

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease and frequently recurs after kidney transplantation. Recurrent FSGS (rFSGS) is associated with poor allograft and patient outcomes. Bleselumab, a fully human immunoglobulin G4 anti-CD40 antagonistic monoclonal antibody, disrupts CD40-related processes in FSGS, potentially preventing rFSGS. METHODS: A phase 2a, randomized, multicenter, open-label study of adult recipients (aged ≥18 y) of a living or deceased donor kidney transplant with a history of biopsy-proven primary FSGS. The study assessed the efficacy of bleselumab combined with tacrolimus and corticosteroids as maintenance immunosuppression in the prevention of rFSGS >12 mo posttransplantation, versus standard of care (SOC) comprising tacrolimus, mycophenolate mofetil, and corticosteroids. All patients received basiliximab induction. The primary endpoint was rFSGS, defined as proteinuria (protein-creatinine ratio ≥3.0 g/g) with death, graft loss, or loss to follow-up imputed as rFSGS, through 3 mo posttransplant. RESULTS: Sixty-three patients were followed for 12 mo posttransplantation. Relative decrease in rFSGS occurrence through 3 mo with bleselumab versus SOC was 40.7% (95% confidence interval, -89.8 to 26.8; P = 0.37; absolute decrease 12.7% [95% confidence interval, -34.5 to 9.0]). Central-blinded biopsy review found relative (absolute) decreases in rFSGS of 10.9% (3.9%), 17.0% (6.2%), and 20.5% (7.5%) at 3, 6, and 12 mo posttransplant, respectively; these differences were not statistically significant. Adverse events were similar for both treatments. No deaths occurred during the study. CONCLUSIONS: In at-risk kidney transplant recipients, bleselumab numerically reduced proteinuria occurrence versus SOC, but no notable difference in occurrence of biopsy-proven rFSGS was observed.


Assuntos
Anticorpos Monoclonais Humanizados , Glomerulosclerose Segmentar e Focal , Imunossupressores , Transplante de Rim , Recidiva , Humanos , Transplante de Rim/efeitos adversos , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Resultado do Tratamento , Tacrolimo/uso terapêutico , Tacrolimo/efeitos adversos , Sobrevivência de Enxerto/efeitos dos fármacos , Quimioterapia Combinada , Corticosteroides/uso terapêutico , Prevenção Secundária/métodos , Falência Renal Crônica/cirurgia , Falência Renal Crônica/prevenção & controle , Falência Renal Crônica/etiologia
16.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(4): 656-660, 2024 Dec 18.
Artigo em Chinês | MEDLINE | ID: mdl-39041561

RESUMO

OBJECTIVE: To explore the clinical safety and effectiveness of self-draining ureteral stent with thread in kidney transplant recipients in renal transplantation. METHODS: This study is a prospective cohort clinical study in the Department of Urology of Peking University People's Hospital from November 2022 to January 2024. The ureteral stent with thread group, in which a 2-0 Mersilene suture of 20-30 cm was used at the bladder end of the ureteral stent during the operation. On the 9th day after the operation, the suture attached to the end of the ureteral stent was expelled out of the urethral orifice with the urine when the catheter was removed. The ureteral stent could be removed along with the suture. As to the cystoscope group, a ureteral stent was routinely placed during kidney transplantation, and the ureteral stent was removed under local infiltration anesthesia through cystoscopy after the operation. The pain scores [numerical rating scale (NRS)-11] during catheter removal and the incidence of urinary tract infections were observed and compared between the two groups. t test was used to compare the pain scores of indwelling ureteral stents and ureteral stents removal between the two groups, and Chi-square test was used to compare the occurrence of urinary system complications within 3 months after operation between the two groups. P < 0.05 was considered statistically significant. RESULTS: As of March 2024, all the recipients were followed up for an average of 6 months (3 to 12 months) postoperatively. A total of 46 kidney transplantation patients were included, with 21 in the ureteral stent with thread group and 25 in the cystoscope group. There were no statistically significant differences between the two groups in age distribution, male-to-female ratio, and deceased versus live donor grafts. Three months after renal transplantation, there were 15 cases of urinary tract infection in the cystoscope group and 4 cases in the ureteral stent with thread group (P=0.007). No significant urinary fistula, wound infection, or ureteral stenosis occurred in either group. No stent-related complications, stent migration, or stone formation were observed. The postoperative bladder spasm symptom scores for indwelling ureteral stents in the cystoscope group and the ureteral stent with thread group were 4.4±2.5 and 4.6±2.4, respectively, with no statistically significant difference (t=0.29, P=0.773). However, the pain scores during ureteral stent removal were 4.9±1.6 and 3.0±1.0 in the two groups, respectively, with a statistically significant diffe-rence (t=5.017, P < 0.001). The total costs of indwelling and removing ureteral stents in the cystoscopy group and the ureteral stent with thread group were 6 452.0 (5 539.5, 6 452.0) yuan and 3 225.0 (3 225.0, 3 225.0) yuan, respectively, and the difference was statistically significant (P < 0.001). CONCLUSION: Compared with the conventional transplanted kidney ureteral stent, the self-discharge ureteral stent technique with sutures is simpler, has a shorter ureteral stent inlay time, reduces the symptoms of bladder spasms, significantly reduces the cost of catheterization, and has fewer postoperative urinary system complications. It is a worthy improved surgical method to be promoted.


Assuntos
Transplante de Rim , Stents , Ureter , Humanos , Transplante de Rim/efeitos adversos , Stents/efeitos adversos , Ureter/cirurgia , Estudos Prospectivos , Feminino , Masculino , Infecções Urinárias/etiologia , Infecções Urinárias/prevenção & controle , Suturas , Pessoa de Meia-Idade
18.
Clin Transplant ; 38(7): e15390, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38973774

RESUMO

BACKGROUND: Extended-spectrum beta-lactamase-producing gram-negative rods (ESBL-GNR) are a rising cause of bacteremia in kidney transplant recipients (KT). The study purpose was to examine patient mortality, allograft survival, estimated glomerular filtration rate (eGFR) at the end of 1 year, and readmission rates while looking at treatment strategies among KTs with ESBL-GNR and non-ESBL-GNR bacteremia at our institution. METHODS: This study was a retrospective, cohort analysis of KTs with gram-negative bacteremia from January 1, 2020, to December 31, 2021. The primary outcome of the study was mortality. Patient outcomes were assessed for 365 days after positive blood cultures. RESULTS: The study included 63 patients. Of these, 18 (29%) patients had bacteremia caused by an ESBL-GNR and 45 (71%) patients had bacteremia caused by a non-ESBL-GNR. Patient survival at 90 days was 94% in the ESBL-GNR group and 96% in the non-ESBL-GNR group. Ciprofloxacin was the most common antimicrobial therapy at discharge (68.9%) in the non-ESBL-GNR group whereas ertapenem was the most common in the ESBL-GNR group (44.5%). Median eGFR at discharge was 41 mL/min/1.73 m2 in the ESBL-GNR group and 48 mL/min/1.73 m2 in the non-ESBL-GNR group. Ninety-day readmission occurred in 9 (50%) ESBL-GNR patients and 14 (32%) non-ESBL-GNR patients. None of the above comparisons are statistically significant (p > 0.05). Eleven (61%) ESBL-GNR and 2 (4%) non-ESBL-GNR patients used outpatient parenteral antimicrobial therapy (p < 0.001). CONCLUSIONS: Among KTs with ESBL-GNR bacteremia, no significant difference was detected in mortality or allograft function compared to non-ESBL-GNR bacteremia.


Assuntos
Bacteriemia , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas , Transplante de Rim , Complicações Pós-Operatórias , beta-Lactamases , Humanos , Masculino , Feminino , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Pessoa de Meia-Idade , beta-Lactamases/metabolismo , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Prognóstico , Seguimentos , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Negativas/efeitos dos fármacos , Fatores de Risco , Taxa de Sobrevida , Sobrevivência de Enxerto , Taxa de Filtração Glomerular , Antibacterianos/uso terapêutico , Testes de Função Renal , Adulto , Falência Renal Crônica/cirurgia , Transplantados
19.
Cochrane Database Syst Rev ; 7: CD004925, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979749

RESUMO

BACKGROUND: Major urological complications (MUCs) after kidney transplantation contribute to patient morbidity and compromise graft function. The majority arise from vesicoureteric anastomosis and present early after transplantation. Ureteric stents have been successfully used to treat such complications. A number of centres have adopted a policy of universal prophylactic stenting at the time of graft implantation to reduce the incidence of urine leaks and ureteric stenosis. Stents are associated with specific complications, and some centres advocate a policy of only stenting selected anastomoses. This is an update of our review, first published in 2005 and last updated in 2013. OBJECTIVES: To examine the benefits and harms of routine ureteric stenting to prevent MUCs in kidney transplant recipients. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant's Specialised Register (up to 19 June 2024) using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Our meta-analysis included all randomised controlled trials (RCTs) and quasi-RCTs designed to examine the impact of using stents for kidney transplant recipients. We aimed to include studies regardless of the type of graft, the technique of ureteric implantation, or the patient group. DATA COLLECTION AND ANALYSIS: Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Twelve studies (1960 patients) were identified. One study was deemed to be at low risk of bias across all domains. The remaining 11 studies were of low or medium quality, with a high or unclear risk of bias in at least one domain. Universal prophylactic ureteric stenting versus control probably reduces major urological complications (11 studies: 1834 participants: RR 0.30, 95% CI 0.16 to 0.55; P < 0.0001; I2 = 16%; moderate certainty evidence; number needed to treat (17)); this benefit was confirmed in the only study deemed to be at low risk of bias across all domains. This benefit was also seen for the individual components of urine leak and ureteric obstruction. Universal prophylactic ureteric stent insertion reduces the risk of MUC in the subgroup of studies with short duration (≤ 14 days) of stenting (2 studies, 480 participants: RR 0.39, 95% CI CI 0.21 to 0.72; P = 0.003; I2 = 0%) and where stenting was continued for > 14 days (8 studies, 124 participants: RR 0.22, 95% CI 0.08 to 0.61; P = 0.004; I2 = 29%). It is uncertain whether stenting has an impact on the development of urinary tract infection (UTI) (10 studies, 1726 participants: RR 1.32, 95% CI 0.97 to 1.80; P = 0.07; I² = 60%; very low certainty evidence due to risk of bias, heterogeneity and imprecision). Subgroup analysis showed that the risk of UTI did not increase if short-duration stenting was used (9 days) and that there was no impact on UTI risk when the prophylactic antibiotic regime co-trimoxazole 480 mg/day was used. Stents appear generally well tolerated, although studies using longer stents (≥ 20 cm) for longer periods (> 6 weeks) had more problems with encrustation and migration. There was no evidence that the presence of a stent resulted in recurrent or severe haematuria (8 studies, 1546 participants: RR 1.09, 95% CI 0.59 to 2.00; P = 0.79; I2 = 33%). The impact of stents on graft and patient survival and other stent-related complications remains unclear as these outcomes were either poorly reported or not reported at all. AUTHORS' CONCLUSIONS: Routine prophylactic stenting probably reduces the incidence of MUCs, even when the duration of stenting is short (≤ 14 days). Further high-quality studies are required to assess optimal stent duration. Studies comparing selective stenting and universal prophylactic stenting, whilst difficult to design and analyse, would address the unresolved quality of life and economic issues.


Assuntos
Transplante de Rim , Complicações Pós-Operatórias , Ensaios Clínicos Controlados Aleatórios como Assunto , Stents , Ureter , Humanos , Stents/efeitos adversos , Transplante de Rim/efeitos adversos , Ureter/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Obstrução Ureteral/prevenção & controle , Cuidados Intraoperatórios/métodos
20.
Sci Rep ; 14(1): 15514, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969704

RESUMO

This study aimed to create and validate a predictive model for renal function following live kidney donation, using pre-donation factors. Accurately predicting remaining renal function post live kidney donation is currently insufficient, necessitating an effective assessment tool. A multicenter retrospective study of 2318 live kidney donors from two independent centers (May 2007-December 2019) was conducted. The primary endpoint was the reduction in eGFR to below 60 mL/min/m2 6 months post-donation. The primary endpoint was achieved in 14.4% of the training cohort and 25.8% of the validation cohort. Sex, age, BMI, hypertension, preoperative eGFR, and remnant kidney proportion (RKP) measured by computerized tomography (CT) volumetry were found significant in the univariable analysis. These variables informed a scoring system based on multivariable analysis: sex (male: 1, female: 0), age at operation (< 30: 0, 30-39: 1, 40-59: 2, ≥ 60: 3), preoperative eGFR (≥ 100: 0, 90-99: 2, 80-89: 4, < 80: 5), and RKP (≥ 52%: 0, < 52%: 1). The total score ranged from 0 to 10. The model showed good discrimination for the primary endpoint in both cohorts. The prediction model provides a useful tool for estimating post-donation renal dysfunction risk, factoring in the side of the donated kidney. It offers potential enhancement to pre-donation evaluations.


Assuntos
Taxa de Filtração Glomerular , Transplante de Rim , Rim , Doadores Vivos , Nefrectomia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Rim/diagnóstico por imagem , Nefrectomia/efeitos adversos , Fatores de Risco , Medição de Risco/métodos , Testes de Função Renal
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