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1.
Kidney Int Rep ; 7(2): 241-250, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35155863

RESUMO

INTRODUCTION: Transplanting kidneys from hepatitis C virus (HCV) viremic donors into HCV-negative patients (HCV D-RNA-positive/R-negative) has evolved from experimental to "standard-of-care" at many centers. Nevertheless, most data derive from single centers and provide only short-term follow-up. METHODS: The Multicenter Study to Transplant Hepatitis C-Infected Kidneys (MYTHIC) study was a multicenter (7 sites) trial of HCV D-RNA-positive/R-negative kidney transplantation (KT) followed by 8 weeks of glecaprevir/pibrentasvir (G/P) initiated 2 to 5 days post-KT. Prespecified outcomes included probability of KT (vs. matched waitlist comparators) and 1-year safety outcomes, allograft function, and survival. RESULTS: Among 63 enrolled patients, 1-year cumulative incidence of KT was approximately 3.5-fold greater for the MYTHIC cohort versus 2055 matched United Network for Organ Sharing (UNOS) comparators who did not opt-in to receive a kidney from an HCV-viremic donor (68% vs. 19%, P < 0.0001). Of 30 HCV D-RNA-positive/R-negative KT recipients, all achieved HCV cure. None developed clinically significant liver disease or HCV-related kidney injury. Furthermore, 1-year survival was 93% and 1-year graft function was excellent (median creatinine 1.17; interquartile range [IQR]: 1.02-1.38 mg/dl). There were 4 cases of cytomegalovirus (CMV) disease among 10 CMV-negative patients transplanted with a kidney from an HCV-viremic/CMV-positive donor. CONCLUSION: The 1-year findings from this multicenter trial suggest that opting-in for HCV-viremic KT offers can increase probability of KT with excellent 1-year outcomes. Trial Registration: NCT03781726.

3.
Lancet Digit Health ; 3(12): e795-e805, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34756569

RESUMO

BACKGROUND: Kidney allograft failure is a common cause of end-stage renal disease. We aimed to develop a dynamic artificial intelligence approach to enhance risk stratification for kidney transplant recipients by generating continuously refined predictions of survival using updates of clinical data. METHODS: In this observational study, we used data from adult recipients of kidney transplants from 18 academic transplant centres in Europe, the USA, and South America, and a cohort of patients from six randomised controlled trials. The development cohort comprised patients from four centres in France, with all other patients included in external validation cohorts. To build deeply phenotyped cohorts of transplant recipients, the following data were collected in the development cohort: clinical, histological, immunological variables, and repeated measurements of estimated glomerular filtration rate (eGFR) and proteinuria (measured using the proteinuria to creatininuria ratio). To develop a dynamic prediction system based on these clinical assessments and repeated measurements, we used a Bayesian joint models-an artificial intelligence approach. The prediction performances of the model were assessed via discrimination, through calculation of the area under the receiver operator curve (AUC), and calibration. This study is registered with ClinicalTrials.gov, NCT04258891. FINDINGS: 13 608 patients were included (3774 in the development cohort and 9834 in the external validation cohorts) and contributed 89 328 patient-years of data, and 416 510 eGFR and proteinuria measurements. Bayesian joint models showed that recipient immunological profile, allograft interstitial fibrosis and tubular atrophy, allograft inflammation, and repeated measurements of eGFR and proteinuria were independent risk factors for allograft survival. The final model showed accurate calibration and very high discrimination in the development cohort (overall dynamic AUC 0·857 [95% CI 0·847-0·866]) with a persistent improvement in AUCs for each new repeated measurement (from 0·780 [0·768-0·794] to 0·926 [0·917-0·932]; p<0·0001). The predictive performance was confirmed in the external validation cohorts from Europe (overall AUC 0·845 [0·837-0·854]), the USA (overall AUC 0·820 [0·808-0·831]), South America (overall AUC 0·868 [0·856-0·880]), and the cohort of patients from randomised controlled trials (overall AUC 0·857 [0·840-0·875]). INTERPRETATION: Because of its dynamic design, this model can be continuously updated and holds value as a bedside tool that could refine the prognostic judgements of clinicians in everyday practice, hence enhancing precision medicine in the transplant setting. FUNDING: MSD Avenir, French National Institute for Health and Medical Research, and Bettencourt Schueller Foundation.


Assuntos
Aloenxertos , Inteligência Artificial , Transplante de Rim , Rim/cirurgia , Modelos Biológicos , Complicações Pós-Operatórias , Insuficiência Renal/diagnóstico , Adulto , Área Sob a Curva , Teorema de Bayes , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteinúria , Insuficiência Renal/cirurgia , Reprodutibilidade dos Testes , Medição de Risco , Transplantados
4.
Clin J Am Soc Nephrol ; 16(10): 1539-1551, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34620649

RESUMO

BACKGROUND AND OBJECTIVES: Subclinical acute rejection is associated with poor outcomes in kidney transplant recipients. As an alternative to surveillance biopsies, noninvasive screening has been established with a blood gene expression profile. Donor-derived cellfree DNA (cfDNA) has been used to detect rejection in patients with allograft dysfunction but not tested extensively in stable patients. We hypothesized that we could complement noninvasive diagnostic performance for subclinical rejection by combining a donor-derived cfDNA and a gene expression profile assay. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a post hoc analysis of simultaneous blood gene expression profile and donor-derived cfDNA assays in 428 samples paired with surveillance biopsies from 208 subjects enrolled in an observational clinical trial (Clinical Trials in Organ Transplantation-08). Assay results were analyzed as binary variables, and then, their continuous scores were combined using logistic regression. The performance of each assay alone and in combination was compared. RESULTS: For diagnosing subclinical rejection, the gene expression profile demonstrated a negative predictive value of 82%, a positive predictive value of 47%, a balanced accuracy of 64%, and an area under the receiver operating curve of 0.75. The donor-derived cfDNA assay showed similar negative predictive value (84%), positive predictive value (56%), balanced accuracy (68%), and area under the receiver operating curve (0.72). When both assays were negative, negative predictive value increased to 88%. When both assays were positive, positive predictive value increased to 81%. Combining assays using multivariable logistic regression, area under the receiver operating curve was 0.81, significantly higher than the gene expression profile (P<0.001) or donor-derived cfDNA alone (P=0.006). Notably, when cases were separated on the basis of rejection type, the gene expression profile was significantly better at detecting cellular rejection (area under the receiver operating curve, 0.80 versus 0.62; P=0.001), whereas the donor-derived cfDNA was significantly better at detecting antibody-mediated rejection (area under the receiver operating curve, 0.84 versus 0.71; P=0.003). CONCLUSIONS: A combination of blood-based biomarkers can improve detection and provide less invasive monitoring for subclinical rejection. In this study, the gene expression profile detected more cellular rejection, whereas donor-derived cfDNA detected more antibody-mediated rejection.


Assuntos
Ácidos Nucleicos Livres/sangue , DNA/sangue , Perfilação da Expressão Gênica , Rejeição de Enxerto/diagnóstico , Transplante de Rim/efeitos adversos , Doadores de Tecidos , Transcriptoma , Adulto , Doenças Assintomáticas , Biomarcadores/sangue , Biópsia , Ácidos Nucleicos Livres/genética , DNA/genética , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Resultado do Tratamento , Estados Unidos , Adulto Jovem
6.
Curr Opin Nephrol Hypertens ; 29(6): 656-662, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32889982

RESUMO

PURPOSE OF REVIEW: The clinical significance and treatment of borderline changes are controversial. The lowest detectable margin for rejection on histology is unclear. We review recent evidence about borderline changes and related biomarkers. RECENT FINDINGS: Borderline change (Banff ≥ t1i1) is associated with progressive fibrosis, a greater propensity to form de-novo DSA, and reduced graft survival. Isolated tubulitis appears to have similar kidney allograft outcomes with normal controls, but this finding should be validated in a larger, diverse population. When borderline change was treated, a higher chance of kidney function recovery and better clinical outcomes were observed. However, spontaneous borderline changes resolution without treatment was also observed. Various noninvasive diagnostic biomarkers have been developed to diagnose subclinical acute rejection, including borderline changes and ≥ Banff 1A TCMR. Biomarkers using gene expression and donor-derived cell-free DNA, and HLA DR/DQ eplet mismatch show potential to diagnose subclinical acute rejection (borderline change and ≥Banff 1A TCMR), to avoid surveillance biopsy, or to predict poor kidney allograft outcomes. SUMMARY: Borderline changes are associated with poor kidney allograft outcomes, but it remains unclear if all cases of borderline changes should be treated. Novel biomarkers may inform physicians to aid in the diagnosis and treatment.


Assuntos
Rejeição de Enxerto , Adulto , Biópsia , Rejeição de Enxerto/diagnóstico , Sobrevivência de Enxerto , Humanos , Rim/patologia , Transplante de Rim , Masculino , Doadores de Tecidos
7.
J Am Soc Nephrol ; 31(11): 2678-2687, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32843477

RESUMO

BACKGROUND: Single-center trials and retrospective case series have reported promising outcomes using kidneys from donors with hepatitis C virus (HCV) infection. However, multicenter trials are needed to determine if those findings are generalizable. METHODS: We conducted a prospective trial at seven centers to transplant 30 kidneys from deceased donors with HCV viremia into HCV-uninfected recipients, followed by 8 weeks of once-daily coformulated glecaprevir and pibrentasvir, targeted to start 3 days posttransplant. Key outcomes included sustained virologic response (undetectable HCV RNA 12 weeks after completing treatment with glecaprevir and pibrentasvir), adverse events, and allograft function. RESULTS: We screened 76 patients and enrolled 63 patients, of whom 30 underwent kidney transplantation from an HCV-viremic deceased donor (median kidney donor profile index, 53%) in May 2019 through October 2019. The median time between consent and transplantation of a kidney from an HCV-viremic donor was 6.3 weeks. All 30 recipients achieved a sustained virologic response. One recipient died of complications of sepsis 4 months after achieving a sustained virologic response. No severe adverse events in any patient were deemed likely related to HCV infection or treatment with glecaprevir and pibrentasvir. Three recipients developed acute cellular rejection, which was borderline in one case. Three recipients developed polyomavirus (BK) viremia near or >10,000 copies/ml that resolved after reduction of immunosuppression. All recipients had good allograft function, with a median creatinine of 1.2 mg/dl and median eGFR of 57 ml/min per 1.73 m2 at 6 months. CONCLUSIONS: Our multicenter trial demonstrated safety and efficacy of transplantation of 30 HCV-viremic kidneys into HCV-negative recipients, followed by early initiation of an 8-week regimen of glecaprevir and pibrentasvir.


Assuntos
Ácidos Aminoisobutíricos/uso terapêutico , Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Ciclopropanos/uso terapêutico , Hepacivirus , Hepatite C/prevenção & controle , Transplante de Rim , Lactamas Macrocíclicas/uso terapêutico , Leucina/análogos & derivados , Prolina/análogos & derivados , Quinoxalinas/uso terapêutico , RNA Viral/sangue , Sulfonamidas/uso terapêutico , Adulto , Aloenxertos/fisiologia , Aloenxertos/virologia , Ácidos Aminoisobutíricos/efeitos adversos , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Ciclopropanos/efeitos adversos , Combinação de Medicamentos , Feminino , Taxa de Filtração Glomerular , Hepatite C/sangue , Humanos , Rim/fisiologia , Lactamas Macrocíclicas/efeitos adversos , Leucina/efeitos adversos , Leucina/uso terapêutico , Masculino , Prolina/efeitos adversos , Prolina/uso terapêutico , Estudos Prospectivos , Pirrolidinas , Quinoxalinas/efeitos adversos , Sulfonamidas/efeitos adversos , Resposta Viral Sustentada
8.
Clin Transplant ; 34(11): e14054, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32738167

RESUMO

Despite the shortage of kidneys for transplantation in the United States, approximately 18%-20% of deceased donor kidneys are discarded each year. These discarded kidneys can offer a survival benefit to suitable patients. Revisions to the current kidney allocation policy may be needed to reduce deceased donor kidney discard. We surveyed transplant physicians and patients to assess their perceived acceptability of policy proposals to reduce the discard of deceased donor kidneys. Members of professional societies (AST, ASTS) and a patient organization (AAKP) were invited to complete the survey. Responses were obtained from 97 physicians and 107 patients. The majority of physicians (73.4%) and patients (73.8%) "somewhat" or "completely" accepted a policy for fast-tracking kidneys at risk of discard. Physicians and patients also supported returning a proportion of waiting time to patients who accept KDPI >85 kidneys and experience graft failure within the first 12 months, with 36% of physicians and 50% of patients electing to return 100% of the waiting time. The majority of physicians (75%) "somewhat or completely" accepted a policy to skip less aggressive centers for KDPI 90 + offers. Physicians and patients provided insights into factors researchers, and policymakers should consider in the design and implementation of these policies.


Assuntos
Transplante de Rim , Médicos , Obtenção de Tecidos e Órgãos , Seleção do Doador , Sobrevivência de Enxerto , Humanos , Rim , Políticas , Fatores de Risco , Doadores de Tecidos , Estados Unidos
10.
Qual Life Res ; 29(11): 3179-3180, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32691349

RESUMO

In its original publication, an erroneous version of Fig. 2d was included in the manuscript. The corrected figure has now been added.

11.
Transplant Proc ; 52(10): 3085-3089, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32576474

RESUMO

An e-mail-based market research survey focused on high-volume US adult transplant centers was developed and implemented to assess surveillance based on United Network for Organ Sharing/Scientific Registry of Transplant Recipients data: 51 to 100 transplants, 101 to 200 transplants, and more than 200 transplants. Eighty-three centers responded to the survey. Respondent centers represented 13,837/21,167 (65%) of the total kidney transplants in 2018. In total, 38/83 (46%) centers reported the use of surveillance biopsies-20 centers in all patients and 18 in select patients. Surveillance biopsies were performed in 37% (7/19) of centers performing 51 to 100 transplants annually, in 44% (15/34) doing 101 to 200 transplants, and in 53% (16/30) of centers doing more than 200 transplants. Of the 20 centers doing surveillance biopsies in all patients, 17/20 (85%) perform more than 100 annual transplants, and 3/20 (15%) perform less than 100 annual transplants. Of the 45 centers not currently doing surveillance biopsies, 13 (29%) used surveillance biopsies in the past; discontinuation was primarily due to patient inconvenience, adverse events, and cost. Using survey percentages, it is estimated that surveillance biopsies are performed in approximately 34% of kidney transplant recipients and that 74% of all surveillance biopsies occur in centers performing more than 100 kidney transplants per year.


Assuntos
Biópsia , Nefropatias/diagnóstico , Transplante de Rim , Padrões de Prática Médica , Transplantes/patologia , Adulto , Humanos , Rim/patologia , Inquéritos e Questionários , Estados Unidos
12.
Qual Life Res ; 29(9): 2355-2374, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32285345

RESUMO

PURPOSE: Living donor kidney transplant (LDKT) imparts the best graft and patient survival for most end-stage kidney disease (ESKD) patients. Yet, there remains variation in post-LDKT health-related quality of life (HRQOL). Improved understanding of post-LDKT HRQOL can help identify patients for interventions to maximize the benefit of LDKT. METHODS: For 477 LDKT recipients transplanted between 11/2007 and 08/2016, we assessed physical, mental, social, and kidney-targeted HRQOL pre-LDKT, as well as 3 and 12 months post-operatively using the SF-36, Kidney Disease Quality of Life-Short Form (KDQOL-SF), and the Functional Assessment of Cancer Therapy-Kidney Symptom Index 19 item version (FKSI-19). We then examined trajectories of each HRQOL domain using latent growth curve models (LGCMs). We also examined associations between decline in HRQOL from 3 months to 12 months post-LDKT and death censored graft failure (DCGF) using Cox regression. RESULTS: Large magnitude effects (d > 0.80) were observed from pre- to post-LDKT change on the SF-36 Vitality scale (d = 0.81) and the KDQOL-SF Burden of Kidney Disease (d = 1.05). Older age and smaller pre- to post-LDKT decreases in serum creatinine were associated with smaller improvements on many HRQOL scales across all domains in LGCMs. Higher DCGF rates were associated with worse physical [e.g., SF-36 PCSoblique hazard ratio (HR) 1.18; 95% CI 1.01-1.38], mental (KDQOL-SF Cognitive Function HR 1.27; 95% CI 1.00-1.62), and kidney-targeted (FKSI-19 HR: 1.18; 95% CI 1.00-1.38) HRQOL domains. CONCLUSION: Clinical HRQOL monitoring may help identify patients who are most likely to have failing grafts and who would benefit from post-LDKT intervention.


Assuntos
Nível de Saúde , Transplante de Rim/psicologia , Qualidade de Vida/psicologia , Transplantados/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Rim/cirurgia , Falência Renal Crônica/terapia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Psicometria , Adulto Jovem
13.
Clin J Am Soc Nephrol ; 14(11): 1670-1676, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31554619

RESUMO

The pretransplant risk assessment for patients with ESKD who are undergoing evaluation for kidney transplant is complex and multifaceted. When considering cardiovascular disease in particular, many factors should be considered. Given the increasing incidence of kidney transplantation and the growing body of evidence addressing ESKD-specific cardiovascular risk profiles, there is an important need for a consolidated, evidence-based model that considers the unique cardiovascular challenges that these patients face. Cardiovascular physiology is altered in these patients by abrupt shifts in volume status, altered calcium-phosphate metabolism, high-output states (in the setting of arteriovenous fistulization), and adverse geometric and electrical remodeling, to name a few. Here, we present a contemporary review by addressing cardiomyopathy/heart failure, pulmonary hypertension, valvular dysfunction, and arrhythmia/sudden cardiac death within the ESKD population.


Assuntos
Doenças Cardiovasculares/complicações , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Transplante de Rim , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/terapia , Humanos , Guias de Prática Clínica como Assunto , Período Pré-Operatório , Medição de Risco
14.
Clin J Am Soc Nephrol ; 14(10): 1493-1499, 2019 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-31537534

RESUMO

BACKGROUND AND OBJECTIVES: The risk of hypertension attributable to living kidney donation remains unknown as does the effect of developing postdonation hypertension on subsequent eGFR. We sought to understand the association between living kidney donation, hypertension, and long-term eGFR by comparing donors with a cohort of healthy nondonors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We compared 1295 living kidney donors with median 6 years of follow-up with a weighted cohort of 8233 healthy nondonors. We quantified the risk of self-reported hypertension using a parametric survival model. We examined the association of hypertension with yearly change in eGFR using multilevel linear regression and clustering by participant, with an interaction term for race. RESULTS: Kidney donation was independently associated with a 19% higher risk of hypertension (adjusted hazard ratio, 1.19; 95% confidence interval, 1.01 to 1.41; P=0.04); this association did not vary by race (interaction P=0.60). For white and black nondonors, there was a mean decline in eGFR (-0.4 and -0.3 ml/min per year, respectively) that steepened after incident hypertension (-0.8 and -0.9 ml/min per year, respectively; both P<0.001). For white and black kidney donors, there was a mean increase in eGFR after donation (+0.4 and +0.6 ml/min per year, respectively) that plateaued after incident hypertension (0 and -0.2 ml/min per year, respectively; P=0.07 and P=0.01, respectively, after hypertension). CONCLUSIONS: Kidney donors are at higher risk of hypertension than similar healthy nondonors, regardless of race. Donors who developed hypertension had a plateau in the usual postdonation increase of eGFR.


Assuntos
Taxa de Filtração Glomerular , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Doadores Vivos , Nefrectomia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Autorrelato , Adulto , Feminino , Humanos , Hipertensão/etiologia , Transplante de Rim , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Nefrectomia/efeitos adversos , Medição de Risco , Fatores de Tempo
15.
Transplantation ; 103(5): 980-989, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30720682

RESUMO

BACKGROUND: Underutilization of marginal-quality kidneys for transplantation produced ideas of expediting kidney placement for populations with decreased opportunities of receiving transplants. Such policies can be less efficacious for specific individuals and should be scrutinized until the decision-making for accepting marginal-quality organs, which has relied on experiential judgment, is better understood at the individual level. There exist rigorous tools promoting personalized decisions with useful and objective information. METHODS: This article introduces a decision-tree methodology that analyzes a patient's dilemma: to accept a kidney offer now or reject it. The methodology calculates the survival benefit of accepting a kidney given a certain quality now and the survival benefit of rejecting it. Survival benefit calculation accounts for patients' and donors' characteristics and transplant centers' and organ procurement organizations' performances and incorporates patients' perceived transplant and dialysis utilities. Valuations of rejecting an offer are contingent on future opportunities and subject to uncertainty in the timing of successive kidney offers and their quality and donor characteristics. RESULTS: The decision tree was applied to a realistic patient profile as a demonstration. The tool was tested on 1000 deceased-donor kidney offers in 2016. Evaluating up to 1 year of future offers, the tool attains 61% accuracy, with transplant utility of 1.0 and dialysis utility of 0.5. The accuracy reveals potential bias in kidney offer acceptance/rejection at transplant centers. CONCLUSIONS: The decision-tree tool presented could aid personalized transplant decision-making in the future by providing patients with calculated, individualized survival benefits between accepting and rejecting a kidney offer.


Assuntos
Árvores de Decisões , Seleção do Doador/métodos , Falência Renal Crônica/terapia , Transplante de Rim/métodos , Modelos Biológicos , Adolescente , Adulto , Idoso , Tomada de Decisões , Feminino , Humanos , Falência Renal Crônica/mortalidade , Transplante de Rim/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Participação do Paciente/métodos , Diálise Renal/estatística & dados numéricos , Alocação de Recursos/métodos , Alocação de Recursos/estatística & dados numéricos , Medição de Risco/métodos , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Transplantes/estatística & dados numéricos , Listas de Espera , Adulto Jovem
16.
Am J Transplant ; 19(1): 98-109, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29985559

RESUMO

Noninvasive biomarkers are needed to monitor stable patients after kidney transplant (KT), because subclinical acute rejection (subAR), currently detectable only with surveillance biopsies, can lead to chronic rejection and graft loss. We conducted a multicenter study to develop a blood-based molecular biomarker for subAR using peripheral blood paired with surveillance biopsies and strict clinical phenotyping algorithms for discovery and validation. At a predefined threshold, 72% to 75% of KT recipients achieved a negative biomarker test correlating with the absence of subAR (negative predictive value: 78%-88%), while a positive test was obtained in 25% to 28% correlating with the presence of subAR (positive predictive value: 47%-61%). The clinical phenotype and biomarker independently and statistically correlated with a composite clinical endpoint (renal function, biopsy-proved acute rejection, ≥grade 2 interstitial fibrosis, and tubular atrophy), as well as with de novo donor-specific antibodies. We also found that <50% showed histologic improvement of subAR on follow-up biopsies despite treatment and that the biomarker could predict this outcome. Our data suggest that a blood-based biomarker that reduces the need for the indiscriminate use of invasive surveillance biopsies and that correlates with transplant outcomes could be used to monitor KT recipients with stable renal function, including after treatment for subAR, potentially improving KT outcomes.


Assuntos
Biomarcadores/sangue , Rejeição de Enxerto/diagnóstico , Transplante de Rim , Adulto , Idoso , Algoritmos , Biópsia , Feminino , Fibrose/diagnóstico , Taxa de Filtração Glomerular , Rejeição de Enxerto/sangue , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Resultado do Tratamento , Adulto Jovem
17.
Am J Transplant ; 19(2): 381-390, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29981209

RESUMO

Currently, the ability to predict or monitor the efficacy of HLA antibody-removal therapies is deficient. We previously reported that titration studies are a consistent and accurate means of assessing antibody strength. To test whether titration studies can also predict which patients are better candidates for desensitization, we studied 38 patients from 3 centers (29 receiving plasmapheresis/low-dose intravenous immunoglobulin [IVIg]; 9 patients receiving high-dose IVIg). For patients undergoing plasmapheresis/low-dose IVIg, antibody titer reduction correlated with number of treatment cycles for both class I and II antibodies but only up to approximately 4 cycles. Reduction in titer slowed with additional cycles, suggesting a limit to the efficacy of this approach. Furthermore, initial titer (predesensitization) can guide the selection of candidates for successful antibody-removal treatment. In our experience, patients with antibodies at an initial titer >1:512 could not be reduced to the goal of a negative lymphocyte crossmatch, corresponding to a 1:16 titer, despite a significant increase in the number of treatment cycles. Change in mean fluorescence intensity (MFI) value did not correlate with success of treatment if initial MFI values were >10 000, likely due to single antigen bead saturation. Overall, we present a potential prognostic tool to predict candidacy and a monitoring tool to assess efficacy of desensitization treatment.


Assuntos
Dessensibilização Imunológica/métodos , Rejeição de Enxerto/prevenção & controle , Antígenos HLA/imunologia , Imunoglobulinas Intravenosas/administração & dosagem , Isoanticorpos/sangue , Transplante de Rim , Plasmaferese/métodos , Adulto , Idoso , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Histocompatibilidade , Humanos , Falência Renal Crônica/cirurgia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
18.
J Cardiovasc Med (Hagerstown) ; 20(2): 51-58, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30540647

RESUMO

: Patients with end-stage renal disease (ESRD) undergoing evaluation for kidney and/or pancreas transplantation represent a population with unique cardiovascular (CV) profiles and unique therapeutic needs. Coronary artery disease (CAD) is common in patients with ESRD, mediated by both the overrepresentation and higher prognostic value of traditional CV risk factors amongst this population, as well as altered cardiovascular responses to failing renal function, likely mediated by dysregulation of the renin-angiotensin-aldosterone system (RAAS) and abnormal calcium and phosphate metabolism. Within the ESRD population, obstructive CAD correlates highly with adverse coronary events, including during the peri-transplant period, and successful revascularization may attenuate some of that increased risk. Accordingly, peri-transplant coronary risk assessment is critical to ensuring optimal outcomes for these patients. The following provides a review of CAD in patients being evaluated for kidney and/or pancreas transplantation, as well as evidence-based recommendations for appropriate peri-transplant evaluation and management.


Assuntos
Doença da Artéria Coronariana/terapia , Falência Renal Crônica/cirurgia , Transplante de Rim , Transplante de Pâncreas , Pancreatopatias/cirurgia , Algoritmos , Tomada de Decisão Clínica , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Técnicas de Apoio para a Decisão , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/fisiopatologia , Transplante de Rim/efeitos adversos , Transplante de Pâncreas/efeitos adversos , Pancreatopatias/complicações , Pancreatopatias/diagnóstico , Pancreatopatias/fisiopatologia , Medição de Risco , Fatores de Risco , Resultado do Tratamento
19.
Transplant Direct ; 4(9): e380, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30234149

RESUMO

Background: Tofacitinib is an oral Janus kinase inhibitor. This open-label, long-term extension (LTE) study (NCT00658359) evaluated long-term tofacitinib treatment in stable kidney transplant recipients (n = 178) posttransplant. Methods: Patients who completed 12 months of cyclosporine (CsA) or tofacitinib treatment in the phase IIb parent study (NCT00483756) were enrolled into this LTE study, evaluating long-term tofacitinib treatment over months 12 to 72 posttransplant. Patients were analyzed by tofacitinib less-intensive (LI) or more-intensive (MI) regimens received in the parent study. For both groups, tofacitinib dose was reduced from 10 to 5 mg twice daily by 6 months into the LTE. Patients were followed up through month 72 posttransplant, with a focus on month 36 results. Results: Tofacitinib demonstrated similar 36-month patient and graft survival rates to CsA. Biopsy-proven acute rejection rates at month 36 were 11.2% for CsA, versus 10.0% and 7.4% (both P > 0.05) for tofacitinib LI and MI, respectively. Least squares mean estimated glomerular filtration rates were 9 to 15 mL/min per 1.73 m2 higher for tofacitinib versus CsA at month 36. The proportions of patients with grade 2/3 interstitial fibrosis and tubular atrophy in month 36 protocol biopsies were 20.0% for LI and 18.2% for MI (both P > 0.05) versus 33.3% for CsA. Kaplan-Meier cumulative serious infection rates at month 36 were numerically higher for tofacitinib LI (43.9%; P = 0.45) and significantly higher for MI (55.9%; P < 0.05) versus CsA (37.1%). Conclusions: Long-term tofacitinib continued to be effective in preventing renal allograft acute rejection and preserving renal function. However, long-term tofacitinib and mycophenolic acid product combination was associated with persistent serious infection risk.

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