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2.
Emerg Med Clin North Am ; 37(4): 679-705, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31563202

RESUMO

Renal transplants are becoming more and more frequent in the United States and worldwide. Studies demonstrate that these patients inevitably end up visiting an emergency department. In addition to typical medical and surgical problems encountered in the general population, this group of patients has unique problems arising from their immunocompromised state and also due to side effects of the medications required. This article discusses these risks and management decisions that the emergency department physician should be aware of in order to prevent adverse outcomes for the patient and transplanted kidney.


Assuntos
Serviço Hospitalar de Emergência , Transplante de Rim/efeitos adversos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/terapia , Humanos , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/terapia
3.
Int J Med Inform ; 130: 103957, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31472443

RESUMO

INTRODUCTION: Machine learning has been increasingly used to develop predictive models to diagnose different disease conditions. The heterogeneity of the kidney transplant population makes predicting graft outcomes extremely challenging. Several kidney graft outcome prediction models have been developed using machine learning, and are available in the literature. However, a systematic review of machine learning based prediction methods applied to kidney transplant has not been done to date. The main aim of our study was to perform an in-depth systematic analysis of different machine learning methods used to predict graft outcomes among kidney transplant patients, and assess their usefulness as an aid to decision-making. METHODS: A systemic review of machine learning methods used to predict graft outcomes among kidney transplant patients was carried out using a search of the Medline, the Cumulative Index to Nursing and Allied Health Literature, EMBASE, PsycINFO and Cochrane databases. RESULTS: A total of 295 articles were identified and extracted. Of these, 18 met the inclusion criteria. Most of the studies were published in the United States after 2010. The population size used to develop the models varied from 80 to 92,844, and the number of features in the models ranged from 6 to 71. The most common machine learning methods used were artificial neural networks, decision trees and Bayesian belief networks. Most of the machine learning based predictive models predicted graft failure with high sensitivity and specificity. Only one machine learning based prediction model had modelled time-to-event (survival) information. Seven studies compared the predictive performance of machine learning models with traditional regression methods and the performance of machine learning methods was found to be mixed, when compared with traditional regression methods. CONCLUSION: There was a wide variation in the size of the study population and the input variables used. However, the prediction accuracy provided mixed results when machine learning and traditional predictive methods are compared. Based on reported gains in predictive performance, machine learning has the potential to improve kidney transplant outcome prediction and aid medical decision making.


Assuntos
Bases de Dados Factuais , Rejeição de Enxerto/diagnóstico , Transplante de Rim/efeitos adversos , Aprendizado de Máquina , Teorema de Bayes , Árvores de Decisões , Rejeição de Enxerto/etiologia , Humanos , Valor Preditivo dos Testes
4.
Transplant Proc ; 51(6): 1699-1705, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399160

RESUMO

BACKGROUND: Rejection and infection are 2 major complications affecting the health and survival of patients receiving an allograft organ transplantation. We describe a diagnostic assay that simultaneously monitors for rejection and infection in recipients of kidney transplant by sequencing of cell-free DNA (cfDNA) in plasma. METHODS: By using cfDNA in plasma, we established a noninvasive method that simultaneously monitors rejection and infection in patients with a history of organ transplant. A total of 6200 single-nucleotide polymorphisms were captured by liquid hybridization and sequenced by next-generation sequencing. The donor-derived cfDNA (ddcfDNA) level was calculated based on maximum likelihood estimation, without relying on the donor's genotype. We also analyzed the nonhuman cfDNA to test for infections in the patients' plasma. RESULTS: Artificial ddcfDNA levels quantified by a donor-dependent and donor-independent algorithm were significantly correlated, with the multivariate coefficient of determination, or R2 value, of 0.999. This technique was applied on 30 patients (32 samples) after kidney transplantation, and a significant difference was observed on the ddcfdNA levels between nonrejection and rejection. Furthermore, 1 BK virus infection and 1 cytomegalovirus infection were revealed by this method, and the enrichment efficiency of the viral sequences was 114 and 489 times, respectively, which are consistent with clinical results. CONCLUSION: This method can be used to simultaneously monitor for acute rejection as well as a broad spectrum of infections for patients of allograft organ transplant because it provides comprehensive information for clinicians to optimize immunosuppression therapy.


Assuntos
Ácidos Nucleicos Livres/sangue , Rejeição de Enxerto/diagnóstico , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Adulto , Algoritmos , Feminino , Rejeição de Enxerto/sangue , Humanos , Hospedeiro Imunocomprometido , /imunologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue
5.
J Cancer Res Clin Oncol ; 145(11): 2779-2791, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31446489

RESUMO

PURPOSE: To evaluate serum procalcitonin (PCT) and C-reactive protein (CRP) as diagnostic biomarkers of transplant-related adverse events (TRAE) in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: This study analyzed PCT and CRP levels of 214 pediatric patients with a median age of 8.5 years (0.4-17.8 years) undergoing allogeneic HSCT with respect to major TRAE. RESULTS: 26 patients (12.1%) did not experience TRAE (control group), and 188 (87.9%) experienced median 2 (range 1-4) TRAE. Median CRP and PCT were highly and significantly increased during sepsis/SIRS and bacteremia (17.24 mg/dl | 6.30 ng/ml; p < 0.0001 vs. prior values), graft rejection (14.73 mg/dl | 3.20 ng/ml; p < 0.0001), and liver GvHD (6.88 mg/dl | 2.29 ng/ml; p < 0.01). Strong CRP increases and slight/minimal/no PCT increases occurred during fungemia (8.85 mg/dl | 0.72 ng/ml; p < 0.001), intestinal GvHD (8.73 mg/dl | 1.06 ng/ml; p < 0.0001), VOD (10.84 mg/dl | 0.59 ng/ml; p < 0.01), mucositis (8.84 mg/dl | 0.81 ng/ml; p < 0.0001), and viremia (3.62 mg/dl; p < 0.0001 | 0.43 ng/ml; below normal limit). During skin GvHD, CRP and PCT were slightly increased (2.03 mg/dl | 0.93 ng/ml; p < 0.0001). CONCLUSIONS: CRP and PCT did not show congruent changes during TRAE. PCT was a clinically relevant marker for the early detection and differentiation of severe mucositis and sepsis/SIRS and bacteremia during the critical neutropenic period after HSCT. PCT helped to discriminate acute intestinal GvHD from adenovirus viremia and liver GvHD from hepatic VOD. Thus, PCT may be a valuable parameter to enable a prompt and appropriate treatment during these complications, improving patient outcomes.


Assuntos
Bacteriemia/diagnóstico , Proteína C-Reativa/análise , Rejeição de Enxerto/diagnóstico , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pró-Calcitonina/sangue , Sepse/diagnóstico , Adolescente , Bacteriemia/sangue , Bacteriemia/etiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Diagnóstico Precoce , Feminino , Seguimentos , Rejeição de Enxerto/sangue , Rejeição de Enxerto/etiologia , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Sepse/sangue , Sepse/etiologia , Transplante Homólogo
6.
Transplant Proc ; 51(8): 2660-2666, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31445765

RESUMO

BACKGROUND: Linear C4d staining in the peritubular capillaries is considered a sensitive and useful marker of active or chronic active antibody-mediated rejection (ABMR) in transplanted kidneys. However, the diagnostic significance of glomerular C4d deposits (gC4d) is still undetermined. The aim of this study is to evaluate the association of gC4d with clinicopathologic features and to assess its diagnostic value. METHODS: From 2013 to 2018, a total of 158 cases of allograft kidney biopsy specimens were obtained from the Korea University Anam Hospital. The histologic features were evaluated according to the Banff classification. The gC4d were determined through immunohistochemical analyses and classified based on scores of 0 to 3 according to the extent of gC4d. RESULTS: A total of 73 cases (46.2%) showed gC4d, and 37 cases (23.4%), 23 cases (14.6%), and 13 cases (8.2%) were classified with a score of 1+, 2+, and 3+, respectively. The gC4d showed a significant correlation with antibody-associated histologic lesions, including peritubular capillaritis, glomerulitis, and transplant glomerulopathy (P < .001). However, gC4d showed no significant association with cell-mediated injuries such as tubulitis, interstitial inflammation, acute tubular necrosis, and thrombotic microangiopathy. Although positive gC4d alone was associated with nonspecific findings without ABMR, most cases of gC4d combined with glomerulitis or transplant glomerulopathy showed typical histologic features of ABMR, clinically with higher antibody titers and severe functional deterioration. CONCLUSIONS: Glomerular C4d deposits may be an alternate useful marker in the diagnosis of active or chronic active ABMR when combined with histologic features of glomerular lesions.


Assuntos
Complemento C4b/análise , Glomerulonefrite/imunologia , Rejeição de Enxerto/diagnóstico , Transplante de Rim/efeitos adversos , Fragmentos de Peptídeos/análise , Complicações Pós-Operatórias/imunologia , Doença Aguda , Adulto , Anticorpos/imunologia , Biomarcadores/análise , Capilares/patologia , Doença Crônica , Complemento C4b/imunologia , Feminino , Glomerulonefrite/patologia , Rejeição de Enxerto/imunologia , Humanos , Rim/imunologia , Glomérulos Renais/imunologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/imunologia , Complicações Pós-Operatórias/patologia , República da Coreia , Microangiopatias Trombóticas/imunologia , Microangiopatias Trombóticas/patologia , Transplante Homólogo
7.
EBioMedicine ; 46: 463-472, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31378695

RESUMO

BACKGROUND: Antibody-mediated rejection, a leading cause of renal allograft graft failure, is diagnosed by histological assessment of invasive allograft biopsies. Accurate non-invasive biomarkers are not available. METHODS: In the multicentre, prospective BIOMARGIN study, blood samples were prospectively collected at time of renal allograft biopsies between June 2011 and August 2016 and analyzed in three phases. The discovery and derivation phases of the study (N = 117 and N = 183 respectively) followed a case-control design and included whole genome transcriptomics and targeted mRNA expression analysis to construct and lock a multigene model. The primary end point was the diagnostic accuracy of the locked multigene assay for antibody-mediated rejection in a third validation cohort of serially collected blood samples (N = 387). This trial is registered with ClinicalTrials.gov, number NCT02832661. FINDINGS: We identified and locked an 8-gene assay (CXCL10, FCGR1A, FCGR1B, GBP1, GBP4, IL15, KLRC1, TIMP1) in blood samples from the discovery and derivation phases for discrimination between cases with (N = 49) and without (N = 134) antibody-mediated rejection. In the validation cohort, this 8-gene assay discriminated between cases with (N = 41) and without antibody-mediated rejection (N = 346) with good diagnostic accuracy (ROC AUC 79·9%; 95% CI 72·6 to 87·2, p < 0·0001). The diagnostic accuracy of the 8-gene assay was retained both at time of stable graft function and of graft dysfunction, within the first year and also later after transplantation. The 8-gene assay is correlated with microvascular inflammation and transplant glomerulopathy, but not with the histological lesions of T-cell mediated rejection. INTERPRETATION: We identified and validated a novel 8-gene expression assay that can be used for non-invasive diagnosis of antibody-mediated rejection. FUNDING: The Seventh Framework Programme (FP7) of the European Commission.


Assuntos
Anticorpos/imunologia , Biomarcadores , Ácidos Nucleicos Livres , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Transplante de Rim/efeitos adversos , RNA Mensageiro/genética , Adulto , Feminino , Rejeição de Enxerto/sangue , Humanos , Biópsia Líquida , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , RNA Mensageiro/sangue , Curva ROC , Reprodutibilidade dos Testes , Transplante Homólogo
9.
Transplant Proc ; 51(6): 1791-1795, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31301854

RESUMO

BACKGROUND: The 2013 Banff meeting updated the requirements for the diagnosis of acute/active antibody-mediated rejection (AAMR) in kidney allografts. There has been speculation that the changes lower the threshold for diagnosing AAMR, and may lead to possible unnecessary and expensive treatment. METHODS: We compared the 2013 Banff classification for AAMR to the previous 2007 Banff to determine if there was an increase in the number of patients receiving a diagnosis of AAMR and if the diagnosis affected allograft survival and post-biopsy 3-month and 6-month creatinine and eGFR values. RESULTS: A total of 212 renal allograft biopsies were compared to both 2007 and 2013 Banff classification requirements for AAMR. Ten patients (11 biopsies) met the 2007 criteria. An additional 15 patients (20 biopsies) met the 2013 criteria. These 2 groups showed no statistically significant demographic differences. By applying the 2013 Banff classification, we observed a 2.5-fold increase in the number of AAMR cases. One-year post-transplant allograft survival was higher in the 2013 group (.85 vs .55) and the 3-month and 6-month post-biopsy creatinine values were significantly lower for the 2013 group (1.6 ± .6 vs 3.3 ± 2.2, P value .01, and 1.7 ± .6 vs 3.4 ± 2.8, P value .03). The 3-month and 6-month eGFR values were higher in the 2013 group, although not statistically significant. CONCLUSIONS: These results suggest that use of Banff 2013 criteria in place of Banff 2007 may result in diagnosing milder and earlier cases of AAMR with the possibility of initiating earlier treatment and improving graft outcomes.


Assuntos
Anticorpos/análise , Rejeição de Enxerto/diagnóstico , Transplante de Rim/efeitos adversos , Escores de Disfunção Orgânica , Adulto , Aloenxertos/imunologia , Aloenxertos/patologia , Anticorpos/imunologia , Biópsia , Creatinina/análise , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto/imunologia , Humanos , Rim/imunologia , Rim/patologia , Masculino , Pessoa de Meia-Idade , Transplante Homólogo , Resultado do Tratamento
11.
Int Rev Immunol ; 38(3): 106-117, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31233364

RESUMO

A growing body of evidence shows that donor-specific antibodies (DSA) are associated with rejection and allograft failure following both liver and intestinal transplantation. However, data have clearly shown that not all DSA are injurious. The reasons for this remain unclear but appear to be multifactorial, impacted by clinical factors such as immunosuppression and infection as well as immunologic factors such as HLA expression and donor-specific antibodies affinity. Establishing a diagnosis of antibody-mediated rejection (AMR) remains clinically challenging, especially given that AMR can present as either acute or chronic graft dysfunction. These observations highlight the need for a better understanding of the immune mechanisms by which DSA and AMR contribute to rejection and allograft failure. This review focuses on current knowledge of DSA and AMR in liver and intestinal transplant recipients and specifically highlights the clinical impact, prevalence, and pathogenesis.


Assuntos
Intestinos/transplante , Isoanticorpos/imunologia , Transplante de Fígado/efeitos adversos , Doadores de Tecidos , Doença Aguda , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Doença Crônica , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/terapia , Antígenos HLA/imunologia , Humanos , Transplante de Fígado/métodos , Prevalência , Fatores de Risco , Transplante Homólogo
12.
Cornea ; 38(8): 970-975, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31135493

RESUMO

PURPOSE: To investigate the effects of graft shift orientation on clinical outcomes after Descemet membrane endothelial keratoplasty (DMEK). METHODS: This study used intraoperative video images to retrospectively examine the effect of graft shift direction in 50 eyes of 50 patients. Correlations were assessed between graft shift direction and multiple parameters. RESULTS: The graft detachment rate was higher in eyes with an inferior graft shift than in those without (superior, 0% and 5.0%; nasal, 0% and 20.0%; inferior, 16.7% and 55.0%; temporal, 16.7% and 45.0%; and any segment, 23.3% and 65.0%; for graft shift-negative and graft shift-positive cases, respectively). Postoperative endothelial cell density reduction was higher in eyes with an inferior graft shift (1 month, 23.6% ± 13.7% and 37.5% ± 18.8%; 3 months, 31.6% ± 16.4% and 45.2% ± 15.2%; and 6 months, 39.8% ± 14.9% and 50.7% ± 16.6%; for graft shift-negative and graft shift-positive cases, respectively). Eyes with a superior graft shift had lower postoperative endothelial cell density reduction than those without (1 month, 36.9% ± 16.6% and 20.0% ± 13.1%; 3 months, 45.3% ± 13.3% and 27.4% ± 16.2%; and 6 months, 51.3% ± 14.6% and 35.9% ± 14.5%; for graft shift-negative and graft shift-positive cases, respectively). Graft shift direction did not affect postoperative best-corrected visual acuity or central corneal thickness. CONCLUSIONS: Graft shift direction in DMEK, especially inferior graft shift, affected the postoperative graft detachment rate. Superior graft shift had a beneficial effect on postoperative corneal endothelial values. These data suggest that inferior graft shift should be avoided in DMEK.


Assuntos
Perda de Células Endoteliais da Córnea/etiologia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Epitélio Posterior/patologia , Rejeição de Enxerto/epidemiologia , Idoso , Contagem de Células , Sobrevivência Celular , Doenças da Córnea/cirurgia , Feminino , Distrofia Endotelial de Fuchs/cirurgia , Rejeição de Enxerto/diagnóstico , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Microscopia com Lâmpada de Fenda , Tomografia de Coerência Óptica , Gravação em Vídeo , Acuidade Visual
13.
Int J Low Extrem Wounds ; 18(2): 208-211, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31035812

RESUMO

Cellulitis is one of the most misdiagnosed disease, which could be lethal when misdiagnosed. There are a lot of diseases to consider in differential diagnosis of cellulitis. Especially when conventional treatment with antibiotics does not seem to work, other radiological examinations and biopsy should be considered to find out what is causing the symptoms. Our case presents a patient with anaplastic large cell lymphoma, who was first thought to have had cellulitis but was later found to have malignancy. We aim to highlight the significance of differential diagnosis in common symptoms.


Assuntos
Celulite (Flegmão)/diagnóstico , Rejeição de Enxerto/diagnóstico , Úlcera da Perna/diagnóstico , Linfoma Anaplásico de Células Grandes/diagnóstico , Idoso de 80 Anos ou mais , Biópsia por Agulha , Celulite (Flegmão)/cirurgia , Desbridamento/métodos , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Úlcera da Perna/cirurgia , Linfoma Anaplásico de Células Grandes/patologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/terapia , Medição de Risco , Transplante de Pele/métodos
14.
Transplant Proc ; 51(5): 1488-1490, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31053345

RESUMO

BACKGROUND: The diagnostic criteria of antibody-mediated rejection (ABMR) has been significantly changed since Banff 2013. The most important revision was adopting microvascular inflammation (MVI) as immunopathologic evidence for ABMR even in C4d-negative cases. In this study, we retrospectively reviewed previous allograft biopsy results and evaluated the impact of this change. METHODS: We reviewed results of 536 renal allograft biopsies at Severance Hospital during 2011 to 2013, which were diagnosed according to the Banff 2009 criteria. All biopsy results were reassessed according to the Banff 2017 criteria. RESULTS: According to the Banff 2009 criteria, antibody-mediated changes were observed in 48 cases out of the 536 allograft biopsies (9.0%). According to the Banff 2017 criteria, 28 additional cases (5.2%) were reclassified as antibody-mediated changes. Twenty-six of these cases were C4d-negative ABMR. The most frequent diagnostic finding in these cases was MVI comprising glomerulitis and peritubular capillaritis. Donor-specific antibodies were investigated in 14 of these cases, which revealed positive results in 12 cases. CONCLUSION: The incidence rate of ABMR has increased after the recent revision of the Banff criteria. The MVI in C4d-negative ABMR cases is the major cause for this increase.


Assuntos
Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/imunologia , Transplante de Rim , Adulto , Feminino , Glomerulonefrite/etiologia , Glomerulonefrite/imunologia , Rejeição de Enxerto/epidemiologia , Humanos , Incidência , Inflamação/etiologia , Inflamação/imunologia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Transplant Rev (Orlando) ; 33(3): 173-181, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31060880

RESUMO

Intestinal transplantation (ITX) constitutes a salvage treatment for irreversible intestinal failure and failure of parenteral nutrition. Chronic rejection (CR) remains the key obstacle for long-term intestinal graft survival but the pathomechanisms are incompletely understood. This study systematically reviews experimental models addressing CR after ITX in order to summarize current knowledge on CR pathogenesis and identify promising experimental strategies. A systematic literature search was conducted in line with the PRISMA guidelines, and 68 out of 677 articles qualified for the final analysis. The average methodological quality of the studies was suboptimal with 7 out of 11 points as assessed by a modified Oxford Centre for Evidence-Based Medicine score. Histology of the chronically rejected graft was almost universally integrated as outcome parameter but we found significant heterogeneity in utilized transplant techniques, organ preservation, immunosuppression and time points of CR-assessment. Several studies identified cellular and humoral immunologic mechanisms in chronic intestinal rejection. Yet, neither preventive nor therapeutic strategies against CR have been successfully introduced into human intestinal transplantation highlighting the persistent need for optimized experimental models. In this review, we aim to improve the translational value of forthcoming investigations on CR by discussing the experimental status quo and potential innovative approaches.


Assuntos
Rejeição de Enxerto/etiologia , Rejeição de Enxerto/terapia , Intestinos/transplante , Transplante de Órgãos/efeitos adversos , Animais , Modelos Animais de Doenças , Rejeição de Enxerto/diagnóstico
16.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1118-1119: 157-163, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31054449

RESUMO

To improve early renal allograft function, it is important to develop a noninvasive diagnostic method for acute T cell-mediated rejection (TCMR). This study aims to explore potential noninvasive urinary biomarkers to screen for acute TCMR in kidney transplant recipients (KTRs) using untargeted metabolomic profiling. Urinary metabolites, collected from KTRs with stable graft function (STA) or acute TCMR episodes, were analyzed using liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical analyses were performed to discriminate differences in urinary metabolites between the two groups. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of potential urinary biomarkers. Statistical analysis revealed the differences in urinary metabolites between the two groups and indicated several statistically significant metabolic features suitable for potential biomarkers. By comparing the retention times and mass fragmentation patterns of the chemicals in metabolite databases, samples, and standards, six of these features were clearly identified. ROC curve analysis showed the best performance of the training set (area under the curve value, 0.926; sensitivity, 90.0%; specificity, 84.6%) using a panel of five potential biomarkers: guanidoacetic acid, methylimidazoleacetic acid, dopamine, 4-guanidinobutyric acid, and L-tryptophan. The diagnostic accuracy of this model was 62.5% for an independent test dataset. LC-MS-based untargeted metabolomic profiling is a promising method to discriminate between acute TCMR and STA groups. Our model, based on a panel of five potential biomarkers, needs to be further validated in larger scale studies.


Assuntos
Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/urina , Transplante de Rim , Metaboloma/fisiologia , Metabolômica/métodos , Adulto , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Feminino , Rejeição de Enxerto/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Linfócitos T/metabolismo , Espectrometria de Massas em Tandem
18.
BMC Immunol ; 20(1): 11, 2019 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-31029086

RESUMO

BACKGROUND: Acute cellular rejection (ACR) is associated with complications after kidney transplantation, such as graft dysfunction and graft loss. Early risk assessment is therefore critical for the improvement of transplantation outcomes. In this work, we retrospectively analyzed a pre-transplant HLA antigen bead assay data set that was acquired by the e:KID consortium as part of a systems medicine approach. RESULTS: The data set included single antigen bead (SAB) reactivity profiles of 52 low-risk graft recipients (negative complement dependent cytotoxicity crossmatch, PRA < 30%) who showed detectable pre-transplant anti-HLA 1 antibodies. To assess whether the reactivity profiles provide a means for ACR risk assessment, we established a novel approach which differs from standard approaches in two aspects: the use of quantitative continuous data and the use of a multiparameter classification method. Remarkably, it achieved significant prediction of the 38 graft recipients who experienced ACR with a balanced accuracy of 82.7% (sensitivity = 76.5%, specificity = 88.9%). CONCLUSIONS: The resultant classifier achieved one of the highest prediction accuracies in the literature for pre-transplant risk assessment of ACR. Importantly, it can facilitate risk assessment in non-sensitized patients who lack donor-specific antibodies. As the classifier is based on continuous data and includes weak signals, our results emphasize that not only strong but also weak binding interactions of antibodies and HLA 1 antigens contain predictive information. TRIAL REGISTRATION: ClinicalTrials.gov NCT00724022 . Retrospectively registered July 2008.


Assuntos
Rejeição de Enxerto/diagnóstico , Teste de Histocompatibilidade/métodos , Transplante de Rim , Doença Aguda , Adulto , Idoso , Feminino , Antígenos HLA/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Isoanticorpos/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade
19.
Transplant Proc ; 51(3): 722-728, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30979456

RESUMO

TruGraf v1 is a laboratory-developed DNA microarray-based gene expression blood test to enable proactive noninvasive serial assessment of kidney transplant recipients with stable renal function. It has been previously validated in patients identified as Transplant eXcellence (TX: stable serum creatinine, normal biopsy results, indicative of immune quiescence), and not-TX (renal dysfunction and/or rejection on biopsy results). TruGraf v1 is intended for use in subjects with stable renal function to measure the immune status as an alternative to invasive, expensive, and risky surveillance biopsies. MATERIALS AND METHODS: In this study, simultaneous blood tests and clinical assessments were performed in 192 patients from 7 transplant centers to evaluate TruGraf v1. The molecular testing laboratory was blinded to renal function and biopsy results. RESULTS: Overall, TruGraf v1 accuracy (concordance between TruGraf v1 result and clinical and/or histologic assessment) was 74% (142/192), and a result of TX was accurate in 116 of 125 (93%). The negative predictive value for TruGraf v1 was 90%, with a sensitivity 74% and specificity of 73%. Results did not significantly differ in patients with a biopsy-confirmed diagnosis vs those without a biopsy. CONCLUSIONS: TruGraf v1 can potentially support a clinical decision enabling unnecessary surveillance biopsies with high confidence, making it an invaluable addition to the transplant physician's tool kit for managing patients. TruGraf v1 testing can potentially avoid painful and risky invasive biopsies, reduce health care costs, and enable frequent assessment of patients with stable renal function to confirm the presence of immune quiescence in the peripheral blood.


Assuntos
Perfilação da Expressão Gênica/métodos , Rejeição de Enxerto/diagnóstico , Transplante de Rim , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Adulto , Biópsia , Feminino , Rejeição de Enxerto/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Transplantados
20.
Transplant Proc ; 51(3): 729-733, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30979457

RESUMO

BACKGROUND: TruGraf v1 is a well-validated DNA microarray-based test that analyzes blood gene expression profiles as an indicator of immune status in kidney transplant recipients with stable renal function. METHODS: In this study, investigators assessed clinical utility of the TruGraf test in patient management. In a retrospective study, simultaneous blood tests and clinical assessments were performed in 192 patients at 7 transplant centers, and in a prospective observational study they were performed in 45 subjects at 5 transplant centers. RESULTS: When queried regarding whether or not the TruGraf test result impacted their decision regarding patient management, in 168 of 192 (87.5%) cases the investigator responded affirmatively. The prospective study indicated that TruGraf results supported physicians' decisions on patient management 87% (39/45) of the time, and in 93% of cases physicians indicated that they would use serial TruGraf testing in future patient management. A total of 21 of 39 (54%) reported results confirmed their decision that no intervention was needed, and 17 of 39 (44%) reported that results specifically informed them that a decision not to perform a surveillance biopsy was correct. CONCLUSIONS: TruGraf is the first and only noninvasive test to be evaluated for clinical utility in determining rejection status of patients with stable renal function and shows promise of providing support for clinical decisions to avoid unnecessary surveillance biopsies with a high degree of confidence. TruGraf is an invaluable addition to the transplant physician's tool kit for managing patient health by avoiding painful and invasive biopsies, reducing health care costs, and enabling frequent assessment of patients with stable renal function to confirm immune quiescence.


Assuntos
Perfilação da Expressão Gênica/métodos , Rejeição de Enxerto/diagnóstico , Transplante de Rim , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Biópsia , Tomada de Decisões , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Patologia Molecular/métodos , Médicos , Estudos Prospectivos , Estudos Retrospectivos
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